Hao He

Xi'an Jiaotong University | XJTU · Department of Civil Engineering

Bone morphogenetic protein (BMP) signaling plays a vital role in differentiation, organogenesis, and various cell processes. As a member of TGF‐β superfamily, the BMP initiation usually accompanies crosstalk with other signaling pathways and simultaneously activates some of them. It is quite challenging to solely initiate an individual pathway. In...

Mitochondrial Ca ²⁺ (mitoCa ²⁺ ) simultaneously implicates respiration, mitochondrial physiology, and cell signaling, which prevents the disentanglement of mitoCa ²⁺ from those complex processes. Although mitochondria have long been recognized as temporary Ca ²⁺ buffer, how mitoCa ²⁺ is regulated and released remains unclear. In this study, we repo...

The airway epithelium is the footstone to maintain the structure and functions of lung, in which resident basal cells (BCs) maintain homeostasis and functional regeneration of epithelial barrier in response to injury. In recent clinical researches, transplanting BCs has shown great inspiring achievements in therapy of various lung diseases. In this...

The technology to induce stem cell differentiation is of great importance in life science, stem cell therapy, and regenerative medicine. Here, we detail steps to noninvasively activate stem cell differentiation in vitro and in vivo using a tightly focused femtosecond laser. We describe how a single-time transient photoactivation can initiate differ...

Wound healing is a long‐term complex process, in which epidermal stem cells (EPSCs) in epidermis of skin have been found to play an essential role in it. We develop a noninvasive method to activate EPSCs in skin in vivo to promote wound healing, based on a microscopic system to enable a sequential frame‐by‐frame scanning of a femtosecond laser at 8...

Circulating tumor cells (CTCs) in blood flow have been believed as an essential biomarker of cancer. The technologies of in vitro and in vivo CTC enrichment and detection suggest although CTCs might play a role of “seed” in metastasis, only the minority of CTCs, probably in the form of CTC clusters, hold the potential to develop a tumor in organs....

A variety of physical and chemical methods have been developed in research laboratories for the induction of stem cell differentiation. However, the use of exogenous chemicals and materials may limit their widespread utility in clinics. To develop a clean and precise induction approach with minimal invasion, we reported here that one‐second stimula...

Ultra-precise stimulation solely to individual mitochondria, without any influence to the whole cell, is quite difficult by traditional biochemical reagents. In mitophagy research, the mitochondria and even the whole cell usually suffer irreversible and great damage caused by treatment with potent chemicals. In this protocol, we present the technic...

Recent technological advancements on stem cell differentiation induction have been making great progress in stem cell research, regenerative medicine, and therapeutic applications. However, the risk of off-target differentiation limits the wide application of stem cell therapy strategies. Here, we report a non-invasive all-optical strategy to induc...

Tumor cells present anti-apoptosis and abnormal proliferation during development. Senescence and stemness of tumor cells play key roles in tumor development and malignancy. In this study, we show the transient stimulation by a single-time scanning of tightly focused femtosecond laser to tumor cells can modulate the stemness and senescence in vitro...

Henoch–Schönlein purpura (HSP) is a typical cutaneous immune skin disease, usually diagnosed by invasive biopsy. In this study, we develop a noninvasive optical method by combining in vivo optical clearing, confocal microscopy and immune-staining together to present the real-time in vivo dynamics of blood vessels, IgA molecules, and T cells in a HS...

Dysregulation of the PINK1/Parkin-mediated mitophagy is essential to Parkinson’s disease. Although important progress has been made in previous researches, the biochemical reagents that induce global and significant mitochondrial damage may still hinder deeper insights into the mechanisms of mitophagy. The origin of PINK1/Parkin pathway activation...

Circulating tumor cells (CTCs) is an established biomarker of cancer metastasis. The circulation dynamics of CTCs are important for understanding the mechanisms underlying tumor cell dissemination. Although studies have revealed that the circadian rhythm may disrupt the growth of tumors, it is generally unclear whether the circadian rhythm controls...

Pulsed lasers at the near infrared (NIR) range have been widely used in dermatology. Ultrashort pulsed picosecond lasers are found with the specific ability of very effective activation of skin repair and remodeling along with significant photodamage. Femtosecond lasers, with a shorter pulse width, may be a promising alternative to current NIR lase...

Ca ²⁺ channels are essential to cell birth, life, and death. They can be externally activated by optogenetic tools, but this requires robust introduction of exogenous optogenetic genes for expression of photosensitive proteins in biological systems. Here we present femtoSOC, a method for direct control of Ca ²⁺ channels solely by ultrafast laser wi...

We demonstrate that our multi-photon stimulation system using ultra-short pulsed laser can modulate molecular signaling system such as changes in [Ca ²⁺ ]i and ROS in mesenchymal stem cells and the expression of early osteoblastic marker could be activated by solely laser illumination in cells 3 days after induction. This project was supported by R...

Femtosecond laser has the characteristics of single pulse energy, high power density. These advantages allow femtosecond laser to be used in biological research. we induced autophagy using femtosecond laser. This result help us further understanding of autophagy.

Presents corrections to author byline and affiliation information to the above named paper.

Mitochondria locate close to endoplasmic reticulum (ER) and cooperate with ER to encode intracellular calcium signaling for cell processes and functions. However, the calcium coupling between mitochondria and ER (mito-ER) remains elusive due to the difficulty of precise excitation of localized mito-ER calcium coupling with little interference to ot...

Gold nanorods (GNRs) can be easily designed and synthesized to respond to photons in the near infrared (NIR) band. The photostimulation by laser irradiation can be mediated and enhanced by GNRs to introduce localized damage to cells for photodynamic/photothermal therapy (PDT or PTT). In this study, we show that cells stained with GNRs can be detect...

The surface plasmon resonance (SPR) sensor is an important tool widely used for studying binding kinetics between biomolecular species. The SPR approach offers unique advantages in light of its real-time and label-free sensing capabilities. Until now, nearly all established SPR instrumentation schemes are based on single- or several-channel configu...

Objective: Visualizing cell interactions in blood circulation is of great importance in studies of anticancer immunotherapy or drugs. However, the lack of a suitable imaging system hampers progress in this field. Methods: In this work, we built a dual-channel in vivo imaging flow cytometer to visualize the interactions of circulating tumor cells...

Circulating tumor cells (CTCs) play a key role in cancer metastasis but are very difficult to detect. in vivo monitoring CTCs has been recognized as an important technique for cancer research and clinical diagnosis. Recently, a noninvasive method, in vivo flow cytometry (IVFC) has been developed to enable continuous, real‐time, and long‐duration de...

Photostimulation In article number 1700137, Minglie Hu, Hao He, and co‐workers demonstrate that a single‐time short flash of femtosecond‐laser stimulation on any target cells can activate the extracellular signal‐regulated kinase (ERK) signaling pathway directly, without any optogenetics or exogenous materials. This optical activation is non‐invasi...

Two-photon microscopy (TPM) has been one of the most widely used fluorescent microscopy methods in biological tissue. The femtosecond laser in the near-infrared (NIR) range showed better penetration in tissue due to less scattering and absorption. The method to estimate the optimal wavelength generally according to the scattering and absorption is...

Optogenetics employs light to manipulate cellular events such as activation of molecular channels, signaling molecules, and gene transcription, by transfection with engineered light‐sensitive proteins. In the last decade, great progresses in life science have been made by optogenetics, but the gene transfection limits its further medical applicatio...

Nanoparticles have been widely used in biomedical research as drug carriers or imaging agents for living animals. Blood circulation is crucial for the delivery of nanoparticles, which enter the bloodstream through injection, inhalation, or dermal exposure. However, the clearance kinetics of nanoparticles in blood circulation has been poorly studied...

Novel 3D barcodes with an extraordinarily high encoding capacity are developed through a flexible, accurate and reproducible method. Here, the three dimensions refer to the size, fluorescence emission wavelength and intensity of the barcodes. As a proof of concept, 3D barcode library with an encoding capacity of 100 flow cytometry-distinguishable b...

The research of mitochondrial dysfunction is of great importance and implicated in a range of neurodegenerative diseases. Traditionally, to investigate mitochondrial dynamics and functions, mitochondria are usually stimulated indirectly by treating cells with exogenous chemicals like oxidative agents. Such treatment lacks precision and controllabil...

Although STAT3 signaling is demonstrated to regulate sensory cell differentiation and regeneration in the zebrafish, its exact role is still unclear in mammalian cochleae. Here, we report that STAT3 and its activated form are specifically expressed in hair cells during mouse cochlear development. Importantly, conditional cochlear deletion of Stat3...

We develop a practical femtosecond polarization-maintaining fiber laser amplification system with a standard double-cladding fiber technique, enabling 24-fs transform-limited pulses with 1-μJ pulse energy at a 1-MHz repetition rate. The laser system is based on a hybrid amplification scheme. Chirped-pulse amplification is employed in the pre-amplif...

In biomedical research fields, the in vivo flow cytometry (IVFC) is a widely used technology which is able to monitor target cells dynamically in living animals. Although the setup of IVFC system has been well established, baseline drift is still a challenge in the process of quantifying circulating cells. Previous methods, i.e., the dynamic peak p...

Tumor cells detached from primary tumor can invade vasculature and form circulating tumor cells (CTCs). Very few of CTCs could be arrested by capillaries. Subsequently, these cells extravasate into distant organs to seed new metastatic colonies. The prognostic significance of CTC numbers has been proved in many kinds of cancer. Even great efforts h...

Circulating tumor cell (CTC) clusters are found among CTCs and show significantly greater potential for an important role in cancer metastasis than single CTCs, which have been traditionally believed as the majority of CTCs. The accurate proportion and dynamics of CTC clusters remain unclear due to the fact that CTCs in blood flow are very difficul...

Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we...

Mid-infrared (mid-IR) (2–20 μm) photonics has numerous chemical and biologic “fingerprint” sensing applications due to characteristic vibrational transitions of molecules in the mid-IR spectral region. Unfortunately, compared to visible light and telecommunication band wavelengths, photonic devices and applications have been difficult to develop at...

Usually, only focused femtosecond (fs) lasers at near-infrared (NIR) range can induce photodamage to transparent cells, making it difficult to treat large amount of cells by such optical methods for photostimulation. In this study, we clarify the mechanism of photodamage to cells that are co-cultured with gold nanorods (GNRs) by fs laser. The pulse...

Melanoma is a malignant tumor of melanocytes. Melanoma cells have high light absorption due to melanin highly contained in melanoma cells. This property is employed for the detection of circulating melanoma cell by in vivo photoacoustic flow cytometry (PAFC), which is based on photoacoustic effect. Compared to in vivo flow cytometry based on fluore...

Mitochondrial research is important to the study of ageing, apoptosis, and metabolic diseases. Over the years, mitochondria have been studied with stimulation by chemical agents in a global manner for basic and applied research. This approach lacks of precision and accuracy in terms of spatial and temporal resolution. Here we demonstrate a direct a...

Two-photon scanning by femtosecond laser on subcellular microregions can induce long-duration Ca2+ increase. The wavelength-dependent spectrum of Ca2+ activation probability suggests endogenous photoactivable molecules which proved to be flavin. Thereby a new all-optical method for photoactivation of cellular Ca2+ can be developed.

The in vivo flow cytometry (IVFC) is now a powerful technique in biomedical research, especially for tracking specific cells in circulatory system. The current fluorescence-based IVFC is limited to visible spectrum, while near infrared (NIR) dyes have their advantages, such as deeper penetration, less absorption and less scattering for NIR fluoresc...

Photostimulation by femtosecond laser can induce nuclear translocation of extracellular signal-regulated protein kinase 2 for activation of specific gene expression. Optical excitation to mitochondria may play a key role in this progress.

Melanoma is a malignant tumor of melanocytes. Circulating melanoma cell has high light absorption due to melanin highly contained in melanoma cells. This property is employed for the detection of circulating melanoma cell by in vivo photoacoustic flow cytometry (PAFC). PAFC is based on photoacoustic effect. Compared to in vivo flow cytometry based...

Mitochondrial research is important to ageing, apoptosis, and mitochondrial diseases. In previous works, mitochondria are usually stimulated indirectly by proapoptotic drugs to study mitochondrial development, which is in lack of controllability, or spatial and temporal resolution. These chemicals or even gene techniques regulating mitochondrial dy...

Laser technology has been promoting various microscopy methods and thus making great progresses in life science. Further than contribution to “seeing is believing”, lasers have also demonstrated their capacity of manipulating cells and even molecular signaling. Specifically, with advances of lasers and combination with other techniques, recent repo...

Multiphoton excitation of femtosecond laser can induce reactive oxygen species bursts in single mitochondrion. Coordinating with mitochondrial permeability transition pores, such oxide bursts can activate the temperate/permanent mitochondrial lesion.

Damaged mitochondria in stem cells have great repair ability when stimulated by femtosecond laser. Mitochondrial membrane potential, reactive oxygen species and mitochondrial permeability transition pores are involved in this process.

For decades, lasers have been a daily tool in most biological research for fluorescent excitation by confocal or multiphoton microscopy. More than 20 years ago, cell photodamage caused by intense laser stimulation was noticed by generating reactive oxygen species, which was then thought as the main damage effect by photons. In this study, we show t...

Controllable gene expression is always a challenge and of great significance to biomedical research and clinical applications. Recently, various approaches based on extra-engineered light-sensitive proteins have been developed to provide optogenetic actuators for gene expression. Complicated biomedical techniques including exogenous genes engineeri...

Femtosecond lasers have been advancing Biophotonics research in the past two decades with multiphoton microscopy, microsurgery, and photodynamic therapy. Nevertheless, laser irradiation is identified to bring photodamage to cells via reactive oxygen species (ROS) generation with unclear mechanism. Meanwhile, currently in biological researches, ther...

Nonlinearity of semiconductor nanowires makes them potential frequency converters in nanoscale optoelectronics. Here we demonstrate that sum frequency generation signals can be acquired from GaAs nanowires when excited by a femtosecond laser at 1048 nm and a tunable optical parametric oscillator ranging from 1416 nm to 1770 nm. The SFG intensity is...

Tightly focused femtosecond laser can induce controllable damage to a single mitochondrion and leading to contraction, fission and swelling at sub-micron level. Mitochondrial membrane potential and reactive oxygen species may play a role in this process.

Femtosecond lasers tightly focused on subcellular microregions can modulate cellular signaling by releasing cellular Ca2+. Life processes of cells including gene regulation, autophagy, and mitochondrial depolarization then take place under such all-optical stimulation.

Nonlinear optical property of semiconductor nanowires plays a key role in nanoscale optoelectronics. In this paper, we demonstrate an excellent frequency converter based on GaAs nanowires (NWs), in which second harmonic generation (SHG) is excited by femtosecond lasers from 800 nm to 1800 nm. Simultaneous SHG with a bandwidth of 300-nm is excited b...

Mitochondria play a key role in all cellular physiology, processes, and behaviors. It is very difficult to precisely stimulate single mitochondria noninvasively in traditional biomedical research. In this study, we report that femtosecond laser can stimulate fragmentation or swelling of single mitochondria in human mesenchymal stem cells rather tha...

Lightening organelles: A femtosecond laser can excite multiphoton-induced luminescence of graphene oxide nanoparticles. The flow, distributions, and clearance of intravenously injected GO-PEG nanoparticles in the blood vessel of mice could be observed clearly by two-photon imaging. The 3D distribution of microinjected GO-PEG nanoparticles in a mice...

Green fluorescent protein (GFP) is one of the most widely studied and exploited proteins in biochemistry and cell biology. It emits fluorescence following optical excitation, which is usually provided by a laser. Here, we report that fluorescence from enhanced GFP can be `turned off' by exposing cells to laser light. A short flash of femtosecond la...

Calcium is a second messenger in all cells for various cellular processes. It was found in astrocytes and neurons that femtosecond laser stimulation could induce Ca2+ wave propagation. In this work, a femtosecond laser with a power above a certain threshold was focused on single HeLa/HEK293T cells for Ca2+ mobilization. Several types of Ca2+ oscill...

In the present paper, we observed both two-photon and three-photon induced distinct photoluminescence from GO nanoparticles under fs laser excitation. Conjugated with PEG molecules, GO nanoparticles exhibited high chemical stability, and could effectively label HeLa cells. Imaged with a two-photon scanning microscope, GO nanoparticles were observed...

We report manipulation of cellular calcium and reactive oxygen species by a femtosecond laser. Modulation of fluorescence conversion from green fluorescence protein and intercellular calcium signaling were thus performed with little side effects.

We demonstrated a femtosecond fiber laser directly delivering high power diffraction-resistant wavepacket. Bessel-Gauss reshaping was obtained by an integrated shaper fabricated on fiber-end by focused ion beam combined with a spherical lens.

We report manipulation of cellular calcium and reactive oxygen species by a femtosecond laser. Modulation of fluorescence conversion from green fluorescence protein and intercellular calcium signaling were thus performed with little side effects.