Sanghuangporus vaninii extract ameliorates hyperlipidemia in rats by mechanisms identified with transcriptome analysis.

The increasing incidence of hyperlipidemia is a serious threat to public health. The development of effective and safe lipid-lowering drugs with few side effects is necessary. The purpose of this study was to assess the lipid-lowering activity of Sanghuangporus vaninii extract (SVE) in rat experiments and reveal the molecular mechanism by transcriptome analysis. Hyperlipidemia was induced in the animals using a high-fat diet for 4 weeks. At the end of the 4th week, hyperlipidemic rats were assigned into two control groups (model and positive simvastatin control) and three treatment groups that received SVE at 200, 400, or 800 mg kg-1 day-1 for another 4 weeks. A last control group comprised normal chow-fed rats. At the end of the 8th week, rats were sacrificed and lipid serum levels, histopathology, and liver transcriptome profiles were determined. SVE was demonstrated to relieve the lipid disorder and improve histopathological liver changes in a dose-dependent manner. The transcriptomic analysis identified changes in hepatocyte gene activity for major pathways including steroid biosynthesis, bile secretion, cholesterol metabolism, AMPK signaling, thyroid hormone signaling, and glucagon signaling. The changed expression of crucial genes in the different groups was confirmed by qPCR. Collectively, this study revealed that SVE could relieve hyperlipidemia in rats, the molecular mechanism might be to promote the metabolism of lipids and the excretion of cholesterol, inhibit the biosynthesis of cholesterol by activating the AMPK signaling pathway, the thyroid hormone signaling pathway, and the glucagon signaling pathway.

FGF13 enhances the function of TRPV1 by stabilizing microtubules and regulates acute and chronic itch.

Itching is an aversive somatosensation that triggers the desire to scratch. Transient receptor potential (TRP) channel proteins are key players in acute and chronic itch. However, whether the modulatory effect of fibroblast growth factor 13 (FGF13) on acute and chronic itch is associated with TRP channel proteins is unclear. Here, we demonstrated that conditional knockout of Fgf13 in dorsal root ganglion neurons induced significant impairment in scratching behaviors in response to acute histamine-dependent and chronic dry skin itch models. Furthermore, FGF13 selectively regulated the function of the TRPV1, but not the TRPA1 channel on Ca2+ imaging and electrophysiological recordings, as demonstrated by a significant reduction in neuronal excitability and current density induced by TRPV1 channel activation, whereas TRPA1 channel activation had no effect. Changes in channel currents were also verified in HEK cell lines. Subsequently, we observed that selective modulation of TRPV1 by FGF13 required its microtubule-stabilizing effect. Furthermore, in FGF13 knockout mice, only the overexpression of FGF13 with a tubulin-binding domain could rescue TRP channel function and the impaired itch behavior. Our findings reveal a novel mechanism by which FGF13 is involved in TRPV1-dependent itch transduction and provide valuable clues for alleviating pathological itch syndrome.

An empirical study on the influence of new generation employees' job satisfaction on contextual performance in the energy industry.

New generation employees in the energy industry generally suffer from several problems such as poor psychological endurance, lack of professional literacy, excessive mental stress, and low labor enthusiasm, which will affect the employee's individual contextual performance and stability of the labor market. In the context of energy transition, therefore, it is of practical significance to solve their problems in routine work and identify the factors affecting the contextual performance of next generation employees in the energy industry. In this paper, the theoretical model with job satisfaction as an independent variable, organizational commitment as a mediator, the sense of self-efficacy as a moderator, and contextual performance as a dependent variable is established; and several research hypotheses are proposed on the basis of the two-factor theory, psychological contract theory, and self-efficacy theory. The following conclusions are made through the testing of hypotheses based on questionnaire investigation: Job satisfaction of new generation employees in the new energy industry positively affects the contextual performance; organizational commitment plays a mediating role between job satisfaction and contextual performance; the sense of self-efficacy plays a role of moderating job satisfaction, organizational commitment, and contextual performance. There is a mediated moderation effect and regulated mediation effect in the model. These conclusions are of great significance to the healthy development of new generation employees in the energy industry.

Successful diagnosis of Mycobacterium marinum infection by mNGS in a patient with Human Immunodeficiency Virus: a case report.

INTRODUCTION: Mycobacterium marinum infection rarely occurs and has atypical symptoms. It is challenging to distinguish disseminated M. marinum infection from multifocal dermatosis caused by other factors clinically. CASE PRESENTATION: Herein, we reported a 68-year-old male patient with Human Immunodeficiency Virus (HIV) who presented redness and swelling in his left hand after being stabbed by marine fish for over 2 months. Mycobacterium tuberculosis infection was considered according to biochemical and pathological examinations, while empirical anti-infection treatment was ineffective. RESULTS: The metagenomic next-generation sequencing (mNGS) detected a large amount of M. marinum sequences, and the patient was finally diagnosed with M. marinum infection. After one month of combination therapy with ethambutol, rifabutin, moxifloxacin, and linezolid, the swelling disappeared significantly. In this case, the successful application of mNGS in diagnosing and treating M. marinum infection has improved the understanding of the microbe both in the laboratory and clinically, especially in patients with HIV. CONCLUSIONS: For diseases with atypical symptoms or difficulty in determining the pathogens, mNGS is suggested in clinical procedures for rapid and accurate diagnosis and treatment.

Analysis of microbial community evolution, autolysis phenomena, and energy metabolism pathways in Pholiota nameko endophytes.

Introduction: Pholiota nameko is a widely consumed edible fungus. This study focuses on two crucial developmental stages of Pholiota nameko, namely, mycelium and ascospores. The objectives of this research were to investigate changes in microbial diversity and community structure during the growth of Pholiota nameko and to analyze the adaptability of the dominant strains to their respective habitats through metabolic. Methods: Specifically, we conducted second-generation sequencing of the 16S rRNA gene (Illumina) on samples obtained from these stages. In addition, we isolated and characterized endophytes present in Pholiota nameko, focusing on examining the impact of dominant endophyte genera on autolysis. We also conducted a metabolic pathway analysis. Results and discussion: The results unveiled 578,414 valid sequences of Pholiota nameko endophytic fungi. At the phylum level, the dominant taxa were Basidiomycota, Ascomycota, Zoopagomycota, and Mucoromycota. At the genus level, the dominant taxa observed were Pholiota, Inocybe, Fusarium, and Hortiboletus. For endophytic bacteria, we obtained 458,475 valid sequences. The dominant phyla were Proteobacteria, TM6, Firmicutes, and Bacteroidetes, while the dominant genera were Edaphobacter, Xanthomonas, Burkholderia, and Pseudomonas. Moreover, we identified the isolated strains in Pholiota nameko using 16S rDNA, and most of them were found to belong to the genus Pseudomonas, with Pseudomonas putida being the most prevalent strain. The findings revealed that the Pseudomonas putida strain has the ability to slow down the breakdown of soluble proteins and partially suppress the metabolic processes that generate superoxide anion radicals in Pholiota nameko, thereby reducing autolysis. Additionally, our results demonstrated that molybdenum enzyme-mediated anaerobic oxidative phosphorylation reactions were the primary energy metabolism pathway in the Pseudomonas putida strain. This suggests that the molybdenum cofactor synthesis pathway might be the main mechanism through which Pholiota nameko adapts to its complex and diverse habitats.

Multiple coherent amplitude modes and exciton-phonon coupling in quasi-one-dimensional excitonic insulator Ta2NiSe5.

An excitonic insulator (EI) is an intriguing correlated electronic phase of condensed excitons. Ta2NiSe5 is a model material for investigating condensed excitonic states. Herein, femtosecond pump-probe spectroscopy is used to study the coherent phonon dynamics and associated exciton-phonon coupling in single-crystal Ta2NiSe5. The reflectivity time series consists of exponential decay due to hot carriers and damped oscillations due to the Ag phonon vibration. Given the in-plane anisotropic thermal conductivity of Ta2NiSe5, coherent phonon oscillations are stronger with perpendicular polarization to its quasi-one-dimensional chains. The 1-, 2-, and 4-THz vibration modes show coherent amplitude responses in the EI phase of Ta2NiSe5 with increasing temperature, totally different from those of normal coherent phonons (the 3- and 3.7-THz modes). The amplitude modes at higher frequencies decouple with the EI order parameter at lower temperatures, as supported by theoretical analysis with a model Hamiltonian of the exciton-phonon coupling system. Our work provides valuable insights into the character of the EI order parameter and its coupling to multiple coherent amplitude modes.

3D-Printed Piezoelectric Stents for Electricity Generation Driven by Pressure Fluctuation.

Vascular stenting is a common procedure used to treat diseased blood vessels by opening the narrowed vessel lumen and restoring blood flow to ischemic tissues in the heart and other organs. In this work, we report a novel piezoelectric stent featuring a zigzag shape fabricated by fused deposition modeling three-dimensional (3D) printing with a built-in electric field. The piezoelectric composite was made of potassium sodium niobite microparticles and poly(vinylidene fluoride-co-hexafluoropropylene), complementing each other with good piezoelectric performance and mechanical resilience. The in situ poling yielded an appreciable piezoelectricity (d33 ∼ 4.2 pC N-1) of the as-printed stents. In vitro testing revealed that materials are nontoxic to vascular cells and have low thrombotic potential. Under stimulated blood pressure fluctuation, the as-printed piezoelectric stent was able to generate peak-to-peak voltage from 0.07 to 0.15 V corresponding to pressure changes from 20 to 120 Psi, giving a sensitivity of 7.02 × 10-4 V Psi-1. Biocompatible piezoelectric stents bring potential opportunities for the real-time monitoring of blood vessels or enabling therapeutic functions.

Theoretical insight into H2O impact on V2O5/TiO2 catalysts for selective catalytic reduction of NOx.

H2O in flue gas causes the deactivation of V2O5/TiO2 catalysts for selective catalytic reduction (SCR) of NOx with NH3 at low temperatures. Developing water resistance requires understanding the theoretical mechanism of H2O impact on the catalysts. The aim of this work was to clarify the adsorption process of H2O and the deactivation mechanism induced by H2O through density functional theory (DFT). The process of H2O adsorption was studied based on a modeled V2O5/TiO2 catalyst surface. It was found that H2O had a strong interaction with exposed titanium atoms. Water adsorption on the catalyst surface significantly alters the electronic structure of VOx sites, transforming Lewis acid sites into Brønsted acid sites. Exposed titanium sites contribute to the decrease of Lewis acidity via adsorbed water. Ab initio thermodynamic calculations show that H2O adsorption on V2O5/TiO2 is stable at low coverage but less favorable at high coverage. Adsorption of NH3 is the most critical step for the SCR of NOx, and the adsorption of H2O can hinder this process. The H2O coverage below 15% of adsorption sites could enhance the NH3 adsorption rate and have a limited effect on the acidity, while higher coverage impeded the adsorption ability of VOx sites. This work provided electron-scale insight into the adsorption impact of H2O on the surface of V2O5/TiO2 catalysts, presented thermodynamic analysis of the adsorption of H2O and NH3, paving the way for the exploration of V2O5/TiO2 catalysts with improved water resistance.

Image Intrinsic-Based Unsupervised Monocular Depth Estimation in Endoscopy.

Unsupervised monocular depth estimation plays a vital role for endoscopy-based minimally invasive surgery (MIS). However, it remains challenging due to the distinctive imaging characteristics of endoscopy which disrupt the assumption of photometric consistency, a foundation relied upon by conventional methods. Distinct from recent approaches taking image pre-processing strategy, this paper introduces a pioneering solution through intrinsic image decomposition (IID) theory. Specifically, we propose a novel end-to-end intrinsic-based unsupervised monocular depth learning framework that is comprised of an image intrinsic decomposition module and a synthesis reconstruction module. This framework seamlessly integrates IID with unsupervised monocular depth estimation, and dedicated losses are meticulously designed to offer robust supervision for network training based on this novel integration. Noteworthy, we rely on the favorable property of the resulting albedo map of IID to circumvent the challenging images characteristics instead of pre-processing the input frames. The proposed method is extensively validated on SCARED and Hamlyn datasets, and better results are obtained than state-of-the-art techniques. Beside, its generalization ability and the effectiveness of the proposed components are also validated. This innovative method has the potential to elevate the quality of 3D reconstruction in monocular endoscopy, thereby enhancing the accuracy and robustness of augmented reality navigation technology in MIS. Our code will be available at: https://github.com/bobo909/IID-SfmLearner.

Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain.

Almost all the neutralizing antibodies targeting the receptor-binding domain (RBD) of spike (S) protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged or emerging variants, such as Omicron and its sub-variants. This suggests that highly conserved epitopes are crucial for the development of neutralizing antibodies. Here, we present one nanobody, N235, displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants, including the newly emerged Omicron and its sub-variants. Cryo-electron microscopy demonstrates N235 binds a novel, conserved, cryptic epitope in the N-terminal domain (NTD) of the S protein, which interferes with the RBD in the neighboring S protein. The neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S complex. Furthermore, a nano-IgM construct (MN235), engineered by fusing N235 with the human IgM Fc region, displays prevention via inducing S1 shedding and cross-linking virus particles. Compared to N235, MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in vitro. The intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo, suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

Monodispersed Bubble Generation Using Hydrophobic Orifices: The Extended Tate's Law.

The use of submerged orifices for bubble generation is ubiquitous in industries with wettability known to influence the bubble departure diameter. In this study, we investigated bubble generation and departure from the orifices (0.3-2 mm) drilled on hydrophobic perfluoroalkoxy (PFA) tubes in water. By varying the gas inflow rate (33 to 200 mL/min), we found that the Sauter mean diameter closely matched those generated by hydrophilic quartz orifices. However, monodispersed bubbles were formed on the PFA tube compared to those on quartz with much wider size distributions. By examining the dynamic bubbling process, we confirmed its agreement with Tate's law, which was originally developed for quasi-steady conditions and emphasizes a balance between capillary and buoyancy forces. However, it should be noted that dynamic conditions lead to an increase in bubble volume compared to the quasi-steady condition despite following the same principle, which is explained by the continuous gas inflow when the bubble departs from the orifice at a necking stage. The above understandings enable generation of monodispersed bubbles under dynamic conditions, benefiting industries requiring precise control on bubble size, such as the bubble assisted wet etching and cleaning processes in semiconductor fabrication.

Clinical value of circulating tumour cells in evaluating the efficacy of continuous hepatic arterial infusion among colorectal cancer patients.

Few studies have been conducted to evaluate the efficacy of HAIC using circulating tumour cells (CTCs). In this study, a total of 100 patients who received HAIC treatment and CTC detection were selected. The results showed that after HAIC treatment, the levels of CTC, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) decreased. Postoperative progression-free survival (PFS) rates between patients with positive and negative preoperative CTC results, and for CA19-9, CEA were significantly different. The positive rate of CTCs was 61% before chemotherapy and 23% after chemotherapy, and the correlation coefficient between the two was 0.385. Those whose CTC values increased after chemotherapy had shorter PFS rates. CTCs are an independent predictor of recurrence. Patients with CTC-positive results are more susceptible to recurrence. The CTC count in peripheral blood has a close bearing on the postoperative chemotherapy efficacy of patients with CRC and affects patients' PFS.

Predefined-Time Output-Feedback Leader-Following Consensus of Pure-Feedback Multiagent Systems.

This article delves into the predefined-time output-feedback leader-following consensus problem of uncertain pure-feedback nonlinear multiagent systems for the first time. To streamline subsequent design, the original systems in pure-feedback form are first transformed into canonical systems. Following this, a distributed predefined-time extended state observer (ESO) and a local predefined-time ESO are developed to reconstruct the unknown states/lumped disturbance of the transformed leader system and follower systems, respectively. Based on the estimated states and utilizing a bounded regulation function, two nonsingular and nonconservative predefined-time control laws are formulated to achieve consensus tracking. The proposed method showcases the following advantages: 1) the actual convergence time rather than the upper bound of the convergence time (UBCT) of the tracking errors can be explicitly specified a priori regardless of the initial conditions in a bounded region, optimizing control energy usage and 2) the system overshoot could be effectively reduced by selecting appropriate parameters for the regulation function. Finally, numerical examples are conducted to verify the obtained results.

Arabidopsis α-Aurora kinase plays a role in cytokinesis through regulating MAP65-3 association with microtubules at phragmoplast midzone.

The α-Aurora kinase is a crucial regulator of spindle microtubule organization during mitosis in plants. Here, we report a post-mitotic role for α-Aurora in reorganizing the phragmoplast microtubule array. In Arabidopsis thaliana, α-Aurora relocated from spindle poles to the phragmoplast midzone, where it interacted with the microtubule cross-linker MAP65-3. In a hypomorphic α-Aurora mutant, MAP65-3 was detected on spindle microtubules, followed by a diffuse association pattern across the phragmoplast midzone. Simultaneously, phragmoplast microtubules remained belatedly in a solid disk array before transitioning to a ring shape. Microtubules at the leading edge of the matured phragmoplast were often disengaged, accompanied by conspicuous retentions of MAP65-3 at the phragmoplast interior edge. Specifically, α-Aurora phosphorylated two residues towards the C-terminus of MAP65-3. Mutation of these residues to alanines resulted in an increased association of MAP65-3 with microtubules within the phragmoplast. Consequently, the expansion of the phragmoplast was notably slower compared to wild-type cells or cells expressing a phospho-mimetic variant of MAP65-3. Moreover, mimicking phosphorylation reinstated disrupted MAP65-3 behaviors in plants with compromised α-Aurora function. Overall, our findings reveal a mechanism in which α-Aurora facilitates cytokinesis progression through phosphorylation-dependent restriction of MAP65-3 associating with microtubules at the phragmoplast midzone.

Genome-wide identification and expression pattern analysis of the GRF transcription factor family in Astragalus mongholicus.

BACKGROUND: Astragalus membranaceus is a plant of the Astragalus genus, which is used as a traditional Chinese herbal medicine with extremely high medicinal and edible value. Astragalus mongholicus, as one of the representative medicinal materials with the same origin of medicine and food, has a rising market demand for its raw materials, but the quality is different in different production areas. Growth-regulating factors (GRF) are transcription factors unique to plants that play important roles in plant growth and development. Up to now, there is no report about GRF in A. mongholicus. METHODS AND RESULTS: This study conducted a genome-wide analysis of the AmGRF gene family, identifying a total of nine AmGRF genes that were classified into subfamily V based on phylogenetic relationships. In the promoter region of the AmGRF gene, we successfully predicted cis-elements that respond to abiotic stress, growth, development, and hormone production in plants. Based on transcriptomic data and real-time quantitative polymerase chain reaction (qPCR) validation, the results showed that AmGRFs were expressed in the roots, stems, and leaves, with overall higher expression in leaves, higher expression of AmGRF1 and AmGRF8 in roots, and high expression levels of AmGRF1 and AmGRF9 in stems. CONCLUSIONS: The results of this study provide a theoretical basis for the further exploration of the functions of AmGRFs in plant growth and development.

Dynamic analyses of a soft tissue-implant interface: Biological responses to immediate versus delayed dental implants.

AIM: To qualitatively and quantitatively evaluate the formation and maturation of peri-implant soft tissues around 'immediate' and 'delayed' implants. MATERIALS AND METHODS: Miniaturized titanium implants were placed in either maxillary first molar (mxM1) fresh extraction sockets or healed mxM1 sites in mice. Peri-implant soft tissues were evaluated at multiple timepoints to assess the molecular mechanisms of attachment and the efficacy of the soft tissue as a barrier. A healthy junctional epithelium (JE) served as positive control. RESULTS: No differences were observed in the rate of soft-tissue integration of immediate versus delayed implants; however, overall, mucosal integration took at least twice as long as osseointegration in this model. Qualitative assessment of Vimentin expression over the time course of soft-tissue integration indicated an initially disorganized peri-implant connective tissue envelope that gradually matured with time. Quantitative analyses showed significantly less total collagen in peri-implant connective tissues compared to connective tissue around teeth around implants. Quantitative analyses also showed a gradual increase in expression of hemidesmosomal attachment proteins in the peri-implant epithelium (PIE), which was accompanied by a significant inflammatory marker reduction. CONCLUSIONS: Within the timeframe examined, quantitative analyses showed that connective tissue maturation never reached that observed around teeth. Hemidesmosomal attachment protein expression levels were also significantly reduced compared to those in an intact JE, although quantitative analyses indicated that macrophage density in the peri-implant environment was reduced over time, suggesting an improvement in PIE barrier functions. Perhaps most unexpectedly, maturation of the peri-implant soft tissues was a significantly slower process than osseointegration.

Potential rapid intraoperative cancer diagnosis using dynamic full-field optical coherence tomography and deep learning: A prospective cohort study in breast cancer patients.

An intraoperative diagnosis is critical for precise cancer surgery. However, traditional intraoperative assessments based on hematoxylin and eosin (H&E) histology, such as frozen section, are time-, resource-, and labor-intensive, and involve specimen-consuming concerns. Here, we report a near-real-time automated cancer diagnosis workflow for breast cancer that combines dynamic full-field optical coherence tomography (D-FFOCT), a label-free optical imaging method, and deep learning for bedside tumor diagnosis during surgery. To classify the benign and malignant breast tissues, we conducted a prospective cohort trial. In the modeling group (n = 182), D-FFOCT images were captured from April 26 to June 20, 2018, encompassing 48 benign lesions, 114 invasive ductal carcinoma (IDC), 10 invasive lobular carcinoma, 4 ductal carcinoma in situ (DCIS), and 6 rare tumors. Deep learning model was built up and fine-tuned in 10,357 D-FFOCT patches. Subsequently, from June 22 to August 17, 2018, independent tests (n = 42) were conducted on 10 benign lesions, 29 IDC, 1 DCIS, and 2 rare tumors. The model yielded excellent performance, with an accuracy of 97.62%, sensitivity of 96.88% and specificity of 100%; only one IDC was misclassified. Meanwhile, the acquisition of the D-FFOCT images was non-destructive and did not require any tissue preparation or staining procedures. In the simulated intraoperative margin evaluation procedure, the time required for our novel workflow (approximately 3 min) was significantly shorter than that required for traditional procedures (approximately 30 min). These findings indicate that the combination of D-FFOCT and deep learning algorithms can streamline intraoperative cancer diagnosis independently of traditional pathology laboratory procedures.

Tetrahydroxy stilbene glucoside rejuvenates aging hematopoietic stem cells with predilection for lymphoid differentiation via AMPK and Tet2.

INTRODUCTION: Aging of hematopoietic stem cells (HSCs) has emerged as an important challenge to human health. Recent advances have raised the prospect of rejuvenating aging HSCs via specific medical interventions, including pharmacological treatments. Nonetheless, efforts to develop such drugs are still in infancy until now. OBJECTIVES: We aimed to screen the prospective agents that can rejuvenate aging HSCs and explore the potential mechanisms. METHODS: We screened a set of natural anti-aging compounds through oral administration to sub-lethally irradiated mice, and identified 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) as a potent rejuvenating agent for aging HSCs. Then naturally aged mice were used for the follow-up assessment to determine the HSC rejuvenating potential of TSG. Finally, based on the transcriptome and DNA methylation analysis, we validated the role of the AMP-activated protein kinase (AMPK)-ten-eleven-translocation 2 (Tet2) axis (the AMPK-Tet2 axis) as the underlying mechanisms of TSG for ameliorating HSCs aging. RESULTS: TSG treatment not only significantly increased the absolute number of common lymphoid progenitors (CLPs) along with B lymphocytes, but also boosted the HSCs/CLPs repopulation potential of aging mice. Further elaborated mechanism research demonstrated that TSG supplementation restored the stemness of aging HSCs, as well as promoted an epigenetic reprograming that was associated with an improved regenerative capacity and an increased rate of lymphopoiesis. Such effects were diminished when the mice were co-treated with an AMPK inhibitor, or when it was performed in Tet2 knockout mice as well as senescent cells assay. CONCLUSION: TSG is effective in rejuvenating aging HSCs by modulating the AMPK- Tet2 axis and thus represents a potential candidate for developing effective HSC rejuvenating therapies.

NIR-II light in clinical oncology: opportunities and challenges.

Novel strategies utilizing light in the second near-infrared region (NIR-II; 900-1,880 nm wavelengths) offer the potential to visualize and treat solid tumours with enhanced precision. Over the past few decades, numerous techniques leveraging NIR-II light have been developed with the aim of precisely eliminating tumours while maximally preserving organ function. During cancer surgery, NIR-II optical imaging enables the visualization of clinically occult lesions and surrounding vital structures with increased sensitivity and resolution, thereby enhancing surgical quality and improving patient prognosis. Furthermore, the use of NIR-II light promises to improve cancer phototherapy by enabling the selective delivery of increased therapeutic energy to tissues at greater depths. Initial clinical studies of NIR-II-based imaging and phototherapy have indicated impressive potential to decrease cancer recurrence, reduce complications and prolong survival. Despite the encouraging results achieved, clinical translation of innovative NIR-II techniques remains challenging and inefficient; multidisciplinary cooperation is necessary to bridge the gap between preclinical research and clinical practice, and thus accelerate the translation of technical advances into clinical benefits. In this Review, we summarize the available clinical data on NIR-II-based imaging and phototherapy, demonstrating the feasibility and utility of integrating these technologies into the treatment of cancer. We also introduce emerging NIR-II-based approaches with substantial potential to further enhance patient outcomes, while also highlighting the challenges associated with imminent clinical studies of these modalities.

Vesicle fusion and release in neurons under dynamic mechanical equilibrium.

Vesicular fusion plays a pivotal role in cellular processes, involving stages like vesicle trafficking, fusion pore formation, content release, and membrane integration or separation. This dynamic process is regulated by a complex interplay of protein assemblies, osmotic forces, and membrane tension, which together maintain a mechanical equilibrium within the cell. Changes in cellular mechanics or external pressures prompt adjustments in this equilibrium, highlighting the system's adaptability. This review delves into the synergy between intracellular proteins, structural components, and external forces in facilitating vesicular fusion and release. It also explores how cells respond to mechanical stress, maintaining equilibrium and offering insights into vesicle fusion mechanisms and the development of neurological disorders.