Simultaneous Modulation of Interface Reinforcement, Crystallization, Anti-Reflection, and Carrier Transport in Sb Gradient-Doped SnO2 /Sb2 S3 Heterostructure for Efficient Photoelectrochemical Cell.

In this study, an effective quadruple optimization integrated synergistic strategy is designed to fabricate quality Sb gradient-doped SnO2 /Sb2 S3 heterostructure for an efficient photoelectrochemical (PEC) cell. The experimental results and theoretical calculations reveal that i) optical absorption matching is realized by combining the anti-reflection of SnO2 and high light absorption ability of Sb2 S3 in the visible region; ii) interface reinforcement is carried out by coordinating gradient-distributed Sb in SnO2 with S in S-rich precursor of Sb2 S3 for improving the Sb2 S3 crystallization process and matching crystalline lattice of Sb:SnO2 and Sb2 S3 ; iii) ultrahigh electron mobility is achieved by making Sb gradient-doped SnO2 ; iv) carrier separation and transport are accelerated by constructing type-II heterojunction with appropriate energy level alignment and forming a high-speed electron transport channel. All of above-mentioned optimization effects are integrated into a synergistic strategy for constructing the Sb:SnO2 /Sb2 S3 photoanode, achieving a photocurrent density of 2.30 mA cm-2 , hydrogen generation rate of 30.03 µmol cm-2 h-1 , and decent working stability. Notably, this method can also be used in other large-scale fabrication processes, such as drop-casting, spray-coating, blade-coating, printing, slot-die, etc. Moreover, this universal integrated strategy paves an avenue to fabricate efficient photoelectrodes with excellent photoelectrochemical performances.

Assembling BH3-mimic peptide into a nanocluster to target intracellular Bcl2 towards the apoptosis induction of cancer cell.

Bcl-2, an anti-apoptotic protein, is always overexpressed in tumor cells to suppress the pro-apoptotic function of Bax, thereby prolonging the life of the tumor. However, BH3 proteins could directly activate Bax via antagonizing Bcl-2 to induce apoptosis in response to the stimulation. Thus, mimicking BH3 proteins with a peptide is a potential strategy for anti-cancer therapy. Unfortunately, clinical translation of BH3-mimic peptide is hindered by its inefficacious cellular internalization and proteolysis resistance. Herein, we translated a BH3-mimic peptide into a peptide-auric spheroidal nanocluster (BH3-AuNp), in which polymeric BH3-Auric precursors [Au1+-S-BH3]narein situself-assembled on the surface of gold nanoparticles by a one-pot synthesis. Expectedly, this strategy could improve the anti-proteolytic ability and cytomembrane penetrability of the BH3 peptide. As a result, BH3-AuNp successfully induced the apoptosis of two cancer cell lines by an order of magnitude compared to BH3. This therapeutic and feasible peptide nano-engineering strategy will help peptides overcome the pharmaceutical obstacles, awaken its biological functions, and possibly revive the research about peptide-derived nanomedicine.

A liquid chromatography-tandem mass spectrometry method for preclinical pharmacokinetics and tissue distribution of hydrolyzable tannins chebulinic acid and chebulagic acid in rats.

A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of chebulinic acid and chebulagic acid in rat plasma and tissues and well used in the pharmacokinetic and tissue distribution studies after intraperitoneal injection administration. Samples were processed with methanol by protein precipitation, and chromatographic separation was performed on an Agilent Zorbax SB-C18 column (50 × 2.1 mm, 1.8 µm) with a mobile phase consisting of methanol and water containing 0.1% formic acid (60:40, v/v). Quantification was performed by selected reaction monitoring with m/z 977.1 → 806.8 for chebulagic acid, m/z 979.0 → 808.7 for chebulinic acid and m/z 851.2 → 704.9 for the internal standard. Good linearity was observed over their respective concentration range. The pharmacokinetic study showed that both compounds reached their peak concentration values (605.8 ± 35.6 ng/mL for chebulinic acid and 1327.1 ± 118.6 ng/mL for chebulagic acid) at the same time of 0.9 h following intraperitoneal injection administration. The two compounds could be detected in blood-abundant tissues. The kidney had the highest concentrations (462.6 ± 138.5 ng/g for chebulinic acid and 1651.7 ± 167.7 ng/g for chebulagic acid) at 1 h post-dose, followed by the heart, liver, spleen and lung.

UPLC-MS/MS determination of flavokawain B, a novel anti-tumor chemotherapeutic agent in rat plasma and its application to a pharmacokinetic study in rats.

A sensitive, selective and rapid ultra-performance liquid chromatography/tandem mass spectrometry method was developed and validated for the quantification of flavokawain B in rat plasma using myrislignan as an internal standard. Sample preparation was accomplished through a protein precipitation extraction process. Chromatographic resolution of flavokawain B and the IS was achieved on an Agilent XDB-C18 column (2.1 × 100 mm, 1.8 µm) using a gradient mobile phase comprising 0.1% formic acid in water and acetonitrile delivered at a flow rate of 0.5 mL/min. Flavokawain B and the IS eluted at 3.27 and 1.96 min, respectively. The total chromatographic run time was 6.0 min. A linear response function was constructed in the concentration range 0.524-1048 ng/mL. Method validation was performed as per the US Food and Drug Administration guidelines and the results met the acceptance criteria. Intra- and inter-day accuracy and precision were in the ranges of -14.3-13.2 and 3.4-11.8%, respectively. Flavokawain B was demonstrated to be stable under various stability conditions. This method has been applied to a pharmacokinetic study in rats.

Pharmacokinetics and tissue distribution of oroxin B in rats using a validated LC-MS/MS assay.

A highly sensitive LC-MS/MS method was developed to measure oroxin B in rat plasma and tissue homogenates. The analyte and IS were isolated from biological matrices by a simple protein precipitation followed by centrifugation. Detection was conducted by electrospray negative-ionization mass spectrometry in selected-reaction monitoring mode. The assay was linear in the concentration range 4.52-904 ng/mL with intra- and inter-day precision of <14.41%. It was successfully applied to the pharmacokinetics and tissue distribution studies of oroxin B after an intravenous dose of 1.0 mg/kg in rats. The results would be useful for further development of oroxin B.

Validated LC-MS/MS method for quantitation of demethylbellidifolin in rat plasma and its application to pharmacokinetic and bioavailability studies.

Demethylbellidifolin, a major xanthone compound of Swertia davidi Franch, shows many beneficial pharmacological effects including antioxidation, anti-inflammation, anti-fibrosis and cardiovascular protection effects. In this research, a rapid and sensitive LC-MS/MS method for the quantitative analysis of demethylbellidifolin in rat plasma was developed. The demethylbellidifolin and internal standard of aurantio-obtusin were extracted from 50 µL of rat plasma samples with ethyl acetate, then the dried residue was reconstituted and injected in an HPLC system with Zorbax SB-C18 analytical column (2.1 × 100 mm, 3.5 µm) and eluted with the mobile phase consisting of methanol and 0.2% formic acid aqueous solution (80:20, v/v). Quantification was performed using a TSQ Quantum Ultra mass spectrometer in negative ESI using selected reaction monitoring mode of the transitions m/z 259.1 → 215.1 for demethylbellidifolin and 329.0 → 314.2 for the IS. Excellent linearity was observed between 1.92 and 960 ng/mL with a limit of quantitation of 1.92 ng/mL. Intra- and inter-day precision (RSD) values of quality control samples were both <8.3%. This study was successfully utilized for the pharmacokinetic profiles of demethylbellidifolin in rats after oral or intravenous administration. The oral bioavailability of demethylbellidifolin was 3.6%.

Quantitative determination of mogroside V in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.

Mogroside V is the most abundant (approximately 0.50%) cucurbitane-type triterpene glycoside in Siraitia grosvenorii and exhibits significant antitussive, expectorant, anti-carcinogenic, and anti-inflammatory effects. A sensitive, robust and selective liquid chromatography tandem with mass spectrometry (LC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of mogroside V in rat plasma. Samples were prepared through an one-step deproteinization procedure with 250 µL of methanol to a 75-µL plasma sample. Plasma samples were effectively separated on a Shiseido Capcell Pak UG120 C18 column (2.0 × 50mm, 3.0µm) using a mobile phase consisting of methanol: water (60:40, v/v) with an isocratic elution program. The running time for each sample was 7.0 min and the elution times of mogroside V and IS were 2.0 and 4.8 min, respectively. The detection relied on a triple-quadrupole tandem with mass spectrometer equipped with negative-ion electrospray ionization interface by selected-reaction monitoring (SRM) of the transitions at m/z 1285.6 → 1123.7 for mogroside V and m/z 1089.6 → 649.6 for IS. The calibration curve was linear over the range of 96.0-96000ng/mL with a limit of quantitation (LOQ) of 96.0ng/mL. Intra-day and inter-day precisions were both <10.1%. Mean recovery and matrix effect of mogroside V in plasma were in the range of 91.3-95.7% and 98.2-105.0%, respectively. This method was successfully applied in the pharmacokinetic study of mogroside V after intravenous or intraperitoneal administration of 1.12mg/kg mogroside V in rats.

Determination of the neuropharmacological drug nodakenin in rat plasma and brain tissues by liquid chromatography tandem mass spectrometry: Application to pharmacokinetic studies.

A rapid and sensitive liquid chromatography tandem mass spectrometry detection using selected reaction monitoring in positive ionization mode was developed and validated for the quantification of nodakenin in rat plasma and brain. Pareruptorin A was used as internal standard. A single step liquid-liquid extraction was used for plasma and brain sample preparation. The method was validated with respect to selectivity, precision, accuracy, linearity, limit of quantification, recovery, matrix effect and stability. Lower limit of quantification of nodakenin was 2.0 ng/mL in plasma and brain tissue homogenates. Linear calibration curves were obtained over concentration ranges of 2.0-1000 ng/mL in plasma and brain tissue homogenates for nodakenin. Intra-day and inter-day precisions (relative standard deviation, RSD) were <15% in both biological media. This assay was successfully applied to plasma and brain pharmacokinetic studies of nodakenin in rats after intravenous administration.

Development and validation of a LC-MS/MS method for determination of pinoresinol diglucoside in rat plasma: Application to pharmacokinetic study.

Pinoresinol diglucoside (PD), a typical marker compound in Ecommia ulmoides Oliv., is an important and natural antihypertensive drug. A selective, sensitive, and rapid liquid chromatography tandem mass spectrometric (LC-MS/MS) analytical method was developed for the determination of PD in rats. After simple protein precipitation with acetonitrile, chromatographic separation of PD was conducted using a reversed-phase ZORBAX SB C18 analytical column (4.6mm × 150 mm, 5 µm particles) with a mobile phase of 10mM ammonium acetate-methanol-acetic acid (50:50:0.15, v/v/v) and quantified by selected reaction monitoring mode under positive electrospray ionization condition. The chromatographic run time was 3.4 min for each sample, in which the retention times of PD and the internal standard were 2.87 and 2.65 min, respectively. The calibration curves were linear over the range of 1.00~3000 ng/mL and the lower limit of quantification was 1.00 ng/mL in rat plasma. The precision expressed by relative standard deviations were <8.9% for intra-batch precision and <2.0% for inter-batch precision, and the intra- and inter-batch accuracy by relative error was within the range of -3.9% ~7.3%, which met acceptable criteria. The LC-MS/MS method was successfully applied to investigate the pharmacokinetics and oral bioavailability of PD in rats, with the bioavailability being only 2.5%.

A highly bioactive THPC-crosslinked recombinant collagen hydrogel implant for aging skin rejuvenation.

Skin aging, a complex physiological progression marked by collagen degradation, poses substantial challenges in dermatology. Recombinant collagen emerges as a potential option for skin revitalization, yet its application is constrained by difficulties in forming hydrogels. We have for the first time developed a highly bioactive Tetrakis(hydroxymethyl) phosphonium chloride (THPC)-crosslinked recombinant collagen hydrogel implant for aging skin rejuvenation. THPC demonstrated superior crosslinking efficiency compared to traditional agents such as EDC/NHS and BDDE, achieving complete recombinant collagen crosslinking at minimal concentrations and effectively inducing hydrogel formation. THPC's four reactive hydroxymethyl groups facilitate robust crosslinking with triple helical recombinant collagen, producing hydrogels with enhanced mechanical strength, excellent injectability, increased stability, and greater durability. Moreover, the hydrogel exhibited remarkable biocompatibility and bioactivity, significantly promoting the proliferation, adhesion, and migration of human foreskin fibroblast-1. In photoaged mice skin models, the THPC-crosslinked collagen hydrogel implant notably improved dermal density, skin elasticity, and reduced transepidermal water loss, creating a conducive environment for fibroblast activity and healthy collagen regeneration. Additionally, it elevated superoxide dismutase (SOD) activity and displayed substantial anti-calcification properties. The THPC-crosslinked recombinant collagen hydrogel implant presents an innovative methodology in combating skin aging, offering significant promise in dermatology and tissue engineering.

A robust acid-resistant chelating polymer for enhanced stabilization of lead ions in fly ash.

Fly ash derived from municipal solid waste incinerators (MSWIs) harbors significant quantities of heavy metals with high leaching toxicity, resulting in detrimental environmental effects. Pb2+ in fly ash is the ion most likely to exceed permissible levels. However, chemical stabilization methods demonstrate poor efficacy in stabilizing Pb2+ under acidic conditions. Herein, we have developed a robust acid-resistant chelating polymer (25DTF) for enhanced stabilization of Pb2+ in fly ash. 25DTF was synthesized through the reaction of formaldehyde with 2,5-dithiourea. 25DTF exhibited remarkable chelation efficiency, nearing 100%, for Pb2+ in fly ash. 25DTF demonstrated exceptional chelation efficiency, surpassing 99.9%, when interacting with Pb2+ in fly ash at pH ≤ 7. Even under acidic conditions, 25DTF effectively prevented the secondary dissolution of Pb2+. Additionally, it indicated outstanding Pb2+ chelation efficiency across diverse regions of China. The 25DTF chelating agent shows considerable potential in alleviating metal ion contamination in soil, wastewater, and urban environmental management, thereby fostering advancements in environmental stewardship.

Engineering a durable BDDE cross-linked collagen filler for skin rejuvenation.

Skin aging, characterized by reduced regeneration, chronic inflammation, and heightened skin cancer risk, poses a significant challenge. Collagen fillers have emerged as a potential solution for skin rejuvenation by stimulating collagen regeneration. However, their clinical efficacy is limited by inherent instability and vulnerability toin vivodegradation by collagenase. Chemical cross-linking presents a promising approach to enhance stability, but it carries risks such as cytotoxicity, calcification, and discoloration. Here, we introduce a highly durable 1,4-butanediol diglycidyl ether (BDDE) cross-linked collagen filler for skin rejuvenation. BDDE effectively cross-links collagen, resulting in fillers with exceptional mechanical strength and injectability. These fillers demonstrate favorable stability and durability, promoting proliferation, adhesion, and spreading of human foreskin fibroblast-1 cellsin vitro. In vivostudies confirm enhanced collagen regeneration without inducing calcification. BDDE cross-linked collagen fillers offer promising prospects for medical cosmetology and tissue regeneration.

Controlled Release of Ceria and Ferric Oxide Nanoparticles via Collagen Hydrogel for Enhanced Osteoarthritis Therapy.

Osteoarthritis (OA), characterized by chronic inflammation and cartilage degeneration, significantly affects over 500 million people globally. Nanoparticles have emerged as promising treatments for OA; however, current strategies often employ a single type of nanoparticle targeting specific disease stages, limiting sustained therapeutic efficacy. In this study, a novel collagen hydrogel is introduced, thiol crosslinked collagen-cerium oxide-poly(D,L-lactic-co-glycolic acid) microspheres encapsulating nanoparticles (CSH-CeO2-pFe2O3), designed for the controlled release of cerium oxide (CeO2) and ferric oxide (Fe2O3) nanoparticles for comprehensive OA management. The sulfhydryl cross-linked collagen matrix embeds CeO2 nanoparticles and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres encapsulating Fe2O3 nanoparticles. The CSH-CeO2-pFe2O3 hydrogel exhibits enhanced mechanical strength and remarkable injectability, along with a significant promotion of cell adhesion, proliferation, and chondrogenic differentiation. Notably, the hydrogel demonstrates intelligent responsiveness to high levels of reactive oxygen species, initiating the rapid release of CeO2 nanoparticles to address the intense inflammatory responses of early-stage OA, followed by the sustained release of Fe2O3 nanoparticles to facilitate cartilage regeneration during the proliferative phase. In a rat model with cartilage defects, the hydrogel significantly alleviates inflammation and enhances cartilage regeneration, holding substantial potential for effectively managing the pathologically complex OA.

A highly biocompatible CE-crosslinked collagen implant with exceptional anti-calcification and collagen regeneration capabilities for aging skin rejuvenation.

Skin aging, a complex and inevitable biological process, results in wrinkles, dermal laxity, and skin cancer, profoundly influencing appearance and overall health. Collagen serves as the fundamental element of the dermal matrix; nevertheless, collagen is susceptible to enzymatic degradation within the body. Crosslinking is employed to enhance the physicochemical properties of collagen. However, conventional crosslinking agents may harbor potential issues such as cytotoxicity and calcification risks, constraining their application in the biomedical field. Therefore, we have for the first time developed a highly biocompatible CE-crosslinked collagen implant with exceptional anti-calcification and collagen regeneration capabilities for aging skin rejuvenation. A novel collagen crosslinking agent (CE) was synthesized through a reaction involving chitosan quaternary ammonium salt with 1,4-butanediol diglycidyl ether. Compared to collagen crosslinked with glutaraldehyde (GA), the CE-crosslinked collagen implant exhibited notable stability and durability. The implant demonstrated excellent injectability and viscosity, resisting displacement after implantation. Additionally, the CE-crosslinked collagen implant displayed superior biocompatibility, effectively promoting the proliferation and adhesion of HFF-1 cells compared with the GA-crosslinked collagen. The CE-crosslinked collagen represented a safer and more biologically active implant material. In vivo experiments further substantiated that the implant significantly facilitated collagen regeneration without inducing calcification. The innovative collagen implant has made substantial strides in enhancing aesthetics and reducing wrinkles, presenting the potential for revolutionary progress in the fields of skin rejuvenation and collagen regeneration.

Injectable and biodegradable collagen-chitosan microspheres for enhanced skin regeneration.

Skin aging is influenced by both external environmental factors and intrinsic biological mechanisms. Traditional microsphere implants aim to rejuvenate aging skin through collagen regeneration, yet their non-biodegradability and risk of granuloma formation often limit their effectiveness. In this study, we developed novel, injectable, highly bioactive, and degradable collagen-chitosan double-crosslinked composite microspheres for skin rejuvenation. The microspheres demonstrated excellent injectability, requiring an injection force of only 0.9 N, and significant biodegradability, effectively degraded in solutions containing phosphate buffer, type I collagenase, and pepsin. In addition, the microspheres exhibited excellent biocompatibility and bioactivity, significantly promoting the proliferation, adhesion, and migration of human foreskin fibroblast-1 (HFF-1) cells. In a photoaged mouse skin model, the implantation of microspheres significantly enhanced dermal density and skin elasticity while reducing transepidermal water loss. Importantly, the implant promoted the regeneration of collagen fibers. This study suggests that collagen-chitosan double-crosslinked composite microspheres hold significant potential for skin rejuvenation treatments.

Agarose-collagen composite microsphere implants: A biocompatible and robust approach for skin tissue regeneration.

Photoaged skin, a consequence of UV radiation-induced collagen degradation, presents a significant challenge for skin rejuvenation. Synthetic polymer microspheres, while offering collagen regeneration potential, carry risks like granulomas. To overcome this, we developed a novel agarose-collagen composite microsphere implant for skin tissue regeneration. Fabricated using an emulsification-crosslinking method, these microspheres exhibited excellent uniformity and sphericity (with a diameter of ~38.5 µm), as well as attractive injectability. In vitro studies demonstrated their superior biocompatibility, promoting cell proliferation, adhesion, and migration. Further assessments revealed favorable biosafety and blood compatibility. In vivo experiments in photoaged mice showed that implantation of these microspheres effectively reduced wrinkles, increased skin density, and improved elasticity by stimulating fibroblast encapsulation and collagen regeneration. These findings highlight the potential of agarose-collagen microspheres in dermatological and tissue engineering applications, offering a safer alternative for skin rejuvenation.

Superwetting Nanofluids of NiOx-Nanocrystals/CsBr Solution for Fabricating Quality NiOx-CsPbBr3 Gradient Hybrid Film in Carbon-Based Perovskite Solar Cells.

The wettability of precursor solution on substrates is the critical factor for fabricating quality film. In this work, superwetting nanofluids (NFs) of non-stoichiometric nickel oxide (NiOx) nanocrystals (NCs)-CsBr solution are first utilized to fabricate quality NiOx-CsPbBr3 hybrid film with gradient-distributed NiOx NCs in the upper part for constructing hole transport ladder in carbon-based perovskite solar cells (C-PSCs). As anticipated, the crystalline properties (improved crystalline grain diameters and reduced impurity phase) and hole extraction/transport of the NiOx-CsPbBr3 hybrid film are improved after incorporating NiOx NCs into CsPbBr3. This originates from the superb wettability of NiOx-CsBr NFs on substrates and the excellent hole-transport properties of NiOx. Consequently, the C-PSCs with the structure of FTO/SnO2/NiOx-CsPbBr3/C displays a power conversion efficiency of 10.07%, resulting in a 23.6% improvement as compared with the pristine CsPbBr3 cell. This work opens up a promising strategy to improve the absorber layer in PSCs by incorporating NCs into perovskite layers through the use of the superwettability of NFs and by composition gradient engineering.

Robust and Efficient Carbon-Based Planar Perovskite Solar Cells with a CsPbBr3-MoS2 Hybrid Absorber.

Optical response improvement and hole transport/extraction enhancement are critical to enhancing the power conversion efficiency (PCE) of carbon electrode-based perovskite solar cells (C-PSCs) with an absorber of CsPbBr3. In this study, a multifunctional optimization method by embedding MoS2 nanosheets in CsPbBr3 bulk to construct a perovskite-nanosheet hybrid structure was presented. A CsPbBr3-MoS2 hybrid film was fabricated by two-step spin-coating the precursor solutions of PbBr2 and CsBr-MoS2 under an ambient atmosphere, where the aqueous solution with highly distributed MoS2 nanosheets was applied as a solvent of the hybrid precursor solution. MoS2 nanosheets were utilized as a p-type modifier and extra absorber to hybridize with CsPbBr3 for improving the CsPbBr3-carbon interface and light absorption ability of the perovskite layer. As expected, the optical response ability, absorber film quality, and carrier separation/extraction/transport properties of C-PSCs were enhanced significantly by embedding MoS2 nanosheets in CsPbBr3 film, which resulted in enhanced C-PSCs properties. Finally, the C-PSCs with the structure of FTO/SnO2/CsPbBr3-MoS2/C presented a champion PCE of 7.87% (active area: 1 cm2), which demonstrated excellent ambient and operational stability. This study provides an efficient method for constructing ultrastable C-PSCs by hybridizing perovskite and nanosheets.

Exercise sensitizes PD-1/PD-L1 immunotherapy as a hypoxia modulator in the tumor microenvironment of melanoma.

Introduction: Hypoxia is associated with unfavorable prognoses in melanoma patients, and the limited response rates of patients to PD-1/PD-L1 blockade could be attributed to the immunosuppressive tumor microenvironment induced by hypoxia. Exercise offers numerous benefits in the anti-tumor process and has the potential to alleviate hypoxia; however, the precise mechanisms through which it exerts its anti-tumor effects remain unclear, and the presence of synergistic effects with PD-1/PD-L1 immunotherapy is yet to be definitively established. Methods: We established a B16F10 homograft malignant melanoma model and implemented two distinct exercise treatments (low/moderate-intensity swim) based on the mice's exercise status. The specific function manner of exercise-induced anti-tumor effects was determined through RNA sequencing and analysis of changes in the tumor microenvironment. Furthermore, moderate-intensity swim that exhibited superior tumor suppression effects was combined with Anti-PD-1 treatment to evaluate its in vivo efficacy in mouse models. Results: Exercise intervention yielded a considerable effect in impeding tumor growth and promoting apoptosis. Immunohistochemistry and RNA sequencing revealed improvements in tumor hypoxia and down-regulation of hypoxia-related pathways. Cellular immunofluorescence and ELISA analyses demonstrated a notable increase of cytotoxic T cell amount and a decrease of regulatory T cells, indicating an improvement of tumor immune microenvironment. In comparison to Anti-PD-1 monotherapy, tumor suppressive efficacy of exercise combination therapy was found to be enhanced with improvements in both the hypoxic tumor microenvironment and T cell infiltration. Conclusion: Exercise has the potential to function as a hypoxia modulator improving the tumor immune microenvironment, resulting in the promotion of anti-tumor efficacy and the facilitation of biologically safe sensitization of PD-1/PD-L1 immunotherapy.

Impact of Internet Use on Mental Health among Elderly Individuals: A Difference-in-Differences Study Based on 2016-2018 CFPS Data.

The number of elderly Internet users has increased significantly in the past few years. However, the impact of Internet use on mental health remains unclear. In this study, we performed a difference-in-differences analysis using data from the 2016 and 2018 waves of the China Family Panel Studies (CFPS) to evaluate the impact of Internet usage on mental health among elderly individuals. A total of 5031 validated respondents were included to explore the relationship between Internet use and reduced levels of depression as well as improved life satisfaction among elderly individuals. The results showed that Internet use significantly reduced depression levels. Unexpectedly, Internet use was not found to improve life satisfaction. Moreover, discontinuing Internet use was not significantly associated with improvements in depression or life satisfaction. More research is needed to fully elucidate the relationship between Internet use and depression levels, as well as life satisfaction among elderly individuals.