Prevalence and genetic diversity of human rhinovirus among patients with acute respiratory infections in China, 2012-2021.

To understand the prevalence of rhinovirus (RV) among acute respiratory infection (ARI) patients, 10-year ARI surveillance in multiple provinces of China were conducted during 2012-2021. Of 15 645 ARI patients, 1180 (7.54%) were confirmed to have RV infection and 820 (69.49%) were children under 5 years of age. RV typing was performed on the 527 VP1 gene sequences, and species A, B, and C accounted for 73.24%, 4.93%, and 21.82%, respectively. Although no significant difference in the proportions of age groups or disease severity was found between RV species, RV-C was more frequently detected in children under 5 years of age, RV-A was more frequently detected in elderly individuals (≥60), and the proportions of pneumonia in RV-A and RV-C patients were higher than those in RV-B patients. The epidemic peak of RV-A was earlier than that of RV-C. A total of 57 types of RV-A, 13 types of RV-B, and 35 types of RV-C were identified in RV-infected patients, and two uncertain RV types were also detected. The findings showed a few differences in epidemiological and clinical features between RV species in ARI patients, and RV-A and RV-C were more prevalent than RV-B.

Endogenous electric field coupling Mxene sponge for diabetic wound management: haemostatic, antibacterial, and healing.

Improper management of diabetic wound effusion and disruption of the endogenous electric field can lead to passive healing of damaged tissue, affecting the process of tissue cascade repair. This study developed an extracellular matrix sponge scaffold (K1P6@Mxene) by incorporating Mxene into an acellular dermal stroma-hydroxypropyl chitosan interpenetrating network structure. This scaffold is designed to couple with the endogenous electric field and promote precise tissue remodelling in diabetic wounds. The fibrous structure of the sponge closely resembles that of a natural extracellular matrix, providing a conducive microenvironment for cells to adhere grow, and exchange oxygen. Additionally, the inclusion of Mxene enhances antibacterial activity(98.89%) and electrical conductivity within the scaffold. Simultaneously, K1P6@Mxene exhibits excellent water absorption (39 times) and porosity (91%). It actively interacts with the endogenous electric field to guide cell migration and growth on the wound surface upon absorbing wound exudate. In in vivo experiments, the K1P6@Mxene sponge reduced the inflammatory response in diabetic wounds, increased collagen deposition and arrangement, promoted microvascular regeneration, Facilitate expedited re-epithelialization of wounds, minimize scar formation, and accelerate the healing process of diabetic wounds by 7 days. Therefore, this extracellular matrix sponge scaffold, combined with an endogenous electric field, presents an appealing approach for the comprehensive repair of diabetic wounds.

ß-Cyclodextrin enhanced bioavailability of petroleum hydrocarbons in industrially contaminated soil: A phytoremediation field study.

Low remediation efficiency due to low bioavailability is a primary restrictive factor for phytoremediation applications. Specifically, this investigation examines whether Suaeda heteroptera Kitagawa (S. heteroptera) can be used in combination with ß-cyclodextrin (ß-CD) to remediate contaminated site. The study was conducted on the growth response of S. heteroptera, bioavailability and dissipation of petroleum hydrocarbons (PHs) in soil under the influence of ß-CD Our preliminary studies confirmed that ß-CD is effective in increasing the biomass and height of plants. The presence of ß-CD could dramatically elevate polycyclic aromatic hydrocarbons (PAHs) and n-alkanes in S. heteroptera. Moreover, a remarkable positive correlation between PHs levels in roots with the dosage of ß-CD and a negative correlation between the PHs levels in roots with KOW of PHs have been observed. The dissipation of n-alkanes was estimated to be 38.73-62.27%, and the dissipation of PAHs was 36.59-60.10%. In addition, the dissipation behavior of n-alkanes and PAHs was well agreement with the first-order kinetic model. These results display that applying ß-CD accelerated the desorption process of PHs from soil and promoted the absorption process of PHs onto the root epidermis. The enhancement of phytoremediation was achieved by increasing the bioavailability of PHs.

There has been an increasing concern regarding soil contamination by petroleum hydrocarbons (PHs) released by industrial activities. The study attempted to investigate how ß-CD affects the phytoremediation of PHs-contaminated sites. The findings of this study offer an environmentally friendly and cost-effective method of phytoremediating industrially contaminated sites using ß-CD enhanced-phytoremediation.

HDAC3 controls male fertility through enzyme-independent transcriptional regulation at the meiotic exit of spermatogenesis.

The transition from meiotic spermatocytes to postmeiotic haploid germ cells constitutes an essential step in spermatogenesis. The epigenomic regulatory mechanisms underlying this transition remain unclear. Here, we find a prominent transcriptomic switch from the late spermatocytes to the early round spermatids during the meiotic-to-postmeiotic transition, which is associated with robust histone acetylation changes across the genome. Among histone deacetylases (HDACs) and acetyltransferases, we find that HDAC3 is selectively expressed in the late meiotic and early haploid stages. Three independent mouse lines with the testis-specific knockout of HDAC3 show infertility and defects in meiotic exit with an arrest at the late stage of meiosis or early stage of round spermatids. Stage-specific RNA-seq and histone acetylation ChIP-seq analyses reveal that HDAC3 represses meiotic/spermatogonial genes and activates postmeiotic haploid gene programs during meiotic exit, with associated histone acetylation alterations. Unexpectedly, abolishing HDAC3 catalytic activity by missense mutations in the nuclear receptor corepressor (NCOR or SMRT) does not cause infertility, despite causing histone hyperacetylation as HDAC3 knockout, demonstrating that HDAC3 enzyme activity is not required for spermatogenesis. Motif analysis of the HDAC3 cistrome in the testes identified SOX30, which has a similar spatiotemporal expression pattern as HDAC3 during spermatogenesis. Depletion of SOX30 in the testes abolishes the genomic recruitment of the HDAC3 to the binding sites. Collectively, these results establish the SOX30/HDAC3 signaling as a key regulator of the transcriptional program in a deacetylase-independent manner during the meiotic-to-postmeiotic transition in spermatogenesis.

Wet depositions of mercury during plum rain season in Taiwan.

The plum rain season in Taiwan is in May and June. The severest plum rain season over the last 21 years was in 2017. This study involves the collection of mercury wet depositions in the plum rain season of May-June in 2017. A DMA-80 (Direct Mercury Analyzer) was used to analyze the precipitated mercury concentrations and calculate the wet depositions of mercury in the plum rain season. The results indicate that the highest wet depositions of mercury in the aqueous phase were on 6/16, reaching 209.04 µg/m2 * day, while the lowest were on 5/15, at 0.18 µg/m2 * day. The mercury wet depositions in the particulate phase were highest on 6/17, when it exceeded 100 µg/kg, and lowest on particulate phase were occurred in 6/11, when it was 3.64 µg/m2 * day. The relationship between the wet depositions of mercury in the aqueous phase and rainfall was insignificant, while that between the wet depositions of mercury in the particulate phase and rainfall was significant. The wet depositions of mercury in this study were second highest (30.73 µg/m2 day) when compared with those in studies in the years 2007-2017. Although the rainfall in this study was only 564 mm H2O, high mercury concentrations obtained from the plum rain season result in the high wet depositions of mercury in Taichung, Taiwan.

Ambient air particulates-bound metallic elements sources identifications during winter and summer at a Science Park.

The ambient air particulates pollutants of total suspended particulates (TSP) and PM2.5 were collected by using PS-1 and Wilbur PM2.5 sampler, simultaneously during the year of 2015-2017 at a photoelectric factory in Science Park of central Taiwan. And those of the ambient air atmospheric metallic elements (Cr, Mn, Ni, Cu, Zn, Pb) concentrations which attached on the TSP and PM2.5 were analyzed by using inductively coupled plasma optical emission spectrometer. In addition, identifying anthropogenic and natural pollutants sources were conducted by using the enrichment factor (EF) and principal component analysis (PCA) methods. The results indicated that the average TSP and PM2.5 concentrations were ranked highest in winter season, while summer season was ranked lowest during the year of 2015-2016. In addition, the average highest metallic element concentrations were occurred in winter season for both TSP and PM2.5 during the year of 2015-2016, while the average lowest metallic elements concentrations in TSP and PM2.5 were also occurred in winter season during the year of 2016-2017. Moreover, the EF analysis results showed that the metallic element Zn came from anthropogenic emission source. As for metallic element Mn, the results showed that metallic element Mn was mainly attributed to natural emission in this study. Finally, the PCA results showed that metallic elements Cr, Zn and Pb were the dominant emissions metallic elements in this study. As for PM2.5, the results showed that the metallic elements Cr, Cu and Pb were the dominant emissions metallic elements at this HPB sampling site.

Review of total suspended particles (TSP) and PM2.5 concentration variations in Asia during the years of 1998-2015.

In Asian countries such as China, Malaysia, Pakistan, India, Taiwan, Korea, Japan and Hong Kong, ambient air total suspended particulates and PM2.5 concentration data were collected and discussed during the years of 1998-2015 in this study. The aim of the present study was to (1) investigate and collect ambient air total suspended particulates (TSP) and PM2.5 concentrations for Asian countries during the past two decades. (2) Discuss, analyze and compare those particulates (TSP and PM2.5) annual concentration distribution trends among those Asian countries during the past two decades. (3) Test the mean concentration differences in TSP and PM2.5 among the Asian countries during the past decades. The results indicated that the mean TSP concentration order was shown as China > Malaysia > Pakistan > India > Taiwan > Korea > Japan. In addition, the mean PM2.5 concentration order was shown as Vietnam > India > China > Hong Kong > Mongolia > Korea > Taiwan > Japan and the average percentages of PM2.5 concentrations for Taiwan, China, Japan, Korea, Hong Kong, Mongolia and Other (India and Vietnam) were 8, 21, 6, 8, 14, 13 and 30%, respectively, during the past two decades. Moreover, t test results revealed that there were significant mean TSP and PM2.5 concentration differences for either China or India to any of the countries such as Taiwan, Korea and Japan in Asia during the past two decades for this study. Noteworthy, China and India are both occupied more than 60% of the TSP and PM2.5 particulates concentrations out of all the Asia countries. As for Taiwan, the average PM2.5 concentration displayed increasing trend in the years of 1998-1999. However, it showed decreasing trend in the years of 2000-2010. As for Korea, the average PM2.5 concentrations showed decreasing trend during the years of 2001-2013. Finally, the average PM2.5 concentrations for Mongolia displayed increasing trend in the years of 2004-2013.

Concentrations and analysis of health risks of ambient air metallic elements at Longjing site in central Taiwan.

The concentrations of particulates and metallic elements that were bound to total suspended particulates in ambient air at Long Cyuan Elementary School (LCYES), Lung Ching Elementary School (LCHES) and Long Shan Primary School (LSPS) sampling sites in the Longjing area were measured. Significant difference tests were conducted at LSPS, LCYES and LCHES sites. Finally, carcinogenic and non-carcinogenic risk values for LSPS, LCYES and LCHES sites in the Longjing district were evaluated. The results show that the most average particulate and metallic element concentrations were highest in October, November, January, February, March, April, August, and September The average particulate and metallic element concentrations at LCHES were higher than at the other sampling sites. The Concentration Scatter Diagrams reveal the absence of significant variation among the LSPS, LCYES and LCHES sampling sites in the Longjing district. Therefore, these sampling sites are inferred to have similar emission sources. The children and adults inhalation carcinogenic risks which referenced US EPA method were all within acceptable ranges. Non-carcinogenic risks revealed that all metallic elements considered herein were harmless to human health.

Individualized dual antiplatelet therapy based on platelet function testing in patients undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials.

BACKGROUND: High on-treatment platelet reactivity (HPR) represents a strong risk factor for thrombotic events after PCI. We aim to evaluate the efficacy and safety of individualizing intensified dual antiplatelet therapy (DAPT) in PCI-treated patients with HPR based on platelet function testing (PFT). METHODS: Electronic databases were searched for randomized control trials that reported the clinical outcomes of using an intensified antiplatelet protocol with P2Y12 receptor inhibitor comparing with standard maintenance dose of clopidogrel on the basis of platelet function testing. Clinical endpoints were assessed. RESULTS: From 2005 to 2016, thirteen clinical studies comprising 7290 patients were included for analysis. Compared with standard antiplatelet therapy with clopidogrel, the intensified protocol based on platelet function testing was associated with a significant reduction in major adverse cardiovascular events (RR:0.55, 95% CI: 0.36-0.84, p = 0.005), cardiovascular death (RR:0.60, 95% CI: 0.38-0.96, p = 0.03), stent thrombosis (RR:0.58, 95% CI: 0.36-0.93, p = 0.02) and target vessel revascularization (RR:0.33, 95% CI: 0.14-0.76, p = 0.009). No significant difference was found in the rate of bleeding events between intensified and standard protocol. CONCLUSIONS: Compared with standard clopidogrel therapy, individualized intensified antiplatelet therapy on the basis of platelet reactivity testing reduces the incidence of cardiovascular events in patient undergoing PCI, without increasing the risk of bleeding.

PM2.5 particulates and metallic elements (Ni, Cu, Zn, Cd and Pb) study in a mixed area of summer season in Shalu, Taiwan.

PM2.5 has become an important environmental issue in Taiwan during the past few years. Moreover, electricity increased significantly during the summertime and TTPP generated by coal burning base is the main electricity provider in central Taiwan. Therefore, summer season has become the main research target in this study. The ambient air concentrations of particulate matter PM2.5 and PM10 collected by using VAPS at a mixed characteristic sampling site were studied in central Taiwan. The results indicated that the average daytime PM2.5 and PM10 particulate concentrations were occurred in May and they were 44.75 and 57.77 µg/m3 in this study. The results also indicated that the average nighttime PM2.5 and PM10 particulate concentrations were occurred in June and they were 38.19 and 45.79 µg/m3 in this study. The average PM2.5/PM10 ratios were 0.7 for daytime, nighttime and 24-h sampling periods in the summer for this study. This value was ranked as the lowest ratios when compared to the other seasons in previous study. Noteworthy, the results further indicated that the metallic element Pb has the mean highest concentrations for 24-h, daytime and nighttime sampling periods when compared to those of the other metallic elements (Ni, Cu, Zn and Cd). The average mean highest metallic Pb concentrations in PM10 were 110.7, 203.0 and 207.2 ng/m3 for 24-h, daytime and nighttime sampling periods in this study. And there were 59.53, 105.2 and 106.6 ng/m3 for Pb in PM2.5 for 24-h, daytime and nighttime sampling periods, respectively. Moreover, the results further indicated that mean metallic element Pb concentrations on PM2.5 and PM10 were all higher than those of the other elements for 24 h, day and nighttime.

Seasonal variations and sources study by way of back trajectories and ANOVA for ambient air pollutants (particulates and metallic elements) within a mixed area at Longjing, central Taiwan: 1-year observation.

This study measured the concentrations of particulates and metallic elements in ambient air by using PS-1 sampler (TSP) at Longjing area. And this study focuses on the collection of ambient air particulates, metallic elements, particulate-bound mercury Hg(p), concentrations. In addition, the sources of ambient pollutants by way of back trajectory analysis are found. Moreover, test mean concentration variance differences for metallic elements (PM, Hg(p), Mn, Fe, Zn, Cr, Cu, and Pb) among the four seasons (spring, summer, autumn and winter) through ANOVA are calculated. The result indicates that the average highest particulate concentration occurred in winter season, and the order was winter > spring > autumn > summer, and the mostly highest average metallic element (Mn, Fe, Zn, Cr, Cu, Pb) concentrations occurred in autumn. Moreover, the mostly average lowest metallic element concentrations occurred in summer. In addition, the above results of backward trajectories that the major particulate pollutants parcel mainly come from northeastern Taiwan. Moreover, when comparing the results of the first half year to that of the second half year, the they indicated that all metallic elements displayed significant differences in concentrations except those of Hg(p), Mn, Fe, Zn. Finally, metallic element Hg(p) is the only one which showed no significant concentration difference from either seasonal variations or half-year observations.

Annual ambient atmospheric mercury speciation measurement from Longjing, a rural site in Taiwan.

The main purpose of this study was to monitor ambient air particulates and mercury species [RGM, Hg(p), GEM and total mercury] concentrations and dry depositions over rural area at Longjing in central Taiwan during October 2014 to September 2015. In addition, passive air sampler and knife-edge surrogate surface samplers were used to collect the ambient air mercury species concentrations and dry depositions, respectively, in this study. Moreover, direct mercury analyzer was directly used to detect the mercury Hg(p) and RGM concentrations. The result indicated that: (1) The average highest RGM, Hg(p), GEM and total mercury concentrations, and dry depositions were observed in January, prevailing dust storm occurred in winter season was the possible major reason responsible for the above findings. (2) The highest average RGM, Hg(p), GEM and total mercury concentrations, dry depositions and velocities were occurred in winter. This is because that China is the largest atmospheric mercury (Hg) emitter in the world. Its Hg emissions and environmental impacts need to be evaluated. (3) The results indicated that the total mercury ratios of Kaohsiung to that of this study were 5.61. This is because that Kaohsiung has the largest industry density (~60 %) in Taiwan. (4) the USA showed average lower mercury species concentrations when compared to those of the other world countries. The average ratios of China/USA values were 89, 76 and 160 for total mercury, RGM and Hg(p), respectively, during the years of 2000-2012.

Generation of Potent Anti-Vascular Endothelial Growth Factor Neutralizing Antibodies from Mouse Phage Display Library for Cancer Therapy.

Vascular endothelial growth factor (VEGF) is an important stimulator for angiogenesis in solid tumors. Blocking VEGF activity is an effective therapeutic strategy to inhibit tumor growth and metastasis. Avastin, a humanized monoclonal antibody recognizes VEGF, has been approved by the US Food and Drug Administration. To generate potential VEGF-recognizing antibodies with better tumor regression ability than that of Avastin, we have designed a systematic antibody selection plan. From mice immunized with recombinant human VEGF, we generated three phage display libraries, scFv-M13KO7, Fab-M13KO7, and scFv-Hyperphage, in single-chain Fv (scFv) or Fab format, displayed using either M13KO7 helper phage or Hyperphage. Solid-phase and solution-phase selection strategies were then applied to each library, generating six panning combinations. A total of sixty-four antibodies recognizing VEGF were obtained. Based on the results of epitope mapping, binding affinity, and biological functions in tumor inhibition, eight antibodies were chosen to examine their abilities in tumor regression in a mouse xenograft model using human COLO 205 cancer cells. Three of them showed improvement in the inhibition of tumor growth (328%-347% tumor growth ratio (% of Day 0 tumor volume) on Day 21 vs. 435% with Avastin). This finding suggests a potential use of these three antibodies for VEGF-targeted therapy.

Infection of influenza virus neuraminidase-vaccinated mice with homologous influenza virus leads to strong protection against heterologous influenza viruses.

Vaccination is the best measure to prevent influenza pandemics. Here, we studied the protective effect against heterologous influenza viruses, including A/reassortant/NYMC X-179A (pH1N1), A/Chicken/Henan/12/2004 (H5N1), A/Chicken/Jiangsu/7/2002 (H9N2) and A/Guizhou/54/89×A/PR/8/34 (A/Guizhou-X) (H3N2), in mice first vaccinated with a DNA vaccine of haemagglutinin (HA) or neuraminidase (NA) of A/PR/8/34 (PR8) and then infected with the homologous virus. We showed that PR8 HA or NA vaccination both protected mice against a lethal dose of the homologous virus; PR8 HA or NA DNA vaccination and then PR8 infection in mice offered poor or excellent protection, respectively, against a second, heterologous influenza virus challenge. In addition, before the second heterologous influenza infection, the highest antibody level against nucleoprotein (NP) and matrix (M1 and M2) proteins was found in the PR8 NA-vaccinated and PR8-infected group. The level of induced cellular immunity against NP and M1 showed a trend consistent with that seen in antibody levels. However, PR8 HA+NA vaccination and then PR8 infection resulted in limited protection against heterologous influenza virus challenge. Results of the present study demonstrated that infection of the homologous influenza virus in mice already immunized with a NA vaccine could provide excellent protection against subsequent infection of a heterologous influenza virus. These findings suggested that NA, a major antigen of influenza virus, could be an important candidate antigen for universal influenza vaccines.

Comparison of multiple DNA vaccines for protection against cytomegalovirus infection in BALB/c mice.

BACKGROUND: Human cytomegalovirus (HCMV) causes serious HCMV-related diseases in immunocompromised people. Vaccination is the most effective measure to control infection with the pathogen, yet no vaccine has been licensed till now. We performed a head-to-head comparison of the protective abilities of multiple DNA vaccines in murine model of murine cytomegalovirus (MCMV) infection. METHODS: Five DNA vaccines were constructed. Four encoding MCMV proteins gp34 (m04), p65 (M84), DNA helicase (M105), and immediate-early 1 protein pp89 (IE-1) , respectively, which were reported to induce CD8+ T cell responses, were compared with the one expressing gB (M55), the neutralizing antibody target antigen, for immune protection in BALB/c mice. Mice were immunized with these DNA vaccines 1 to 4 times via intramuscular injection followed by electroporation, and were subsequently infected with a lethal dose (3 × LD50) of highly virulent SG-MCMV. Specific antibodies and IFN-γ secreting splenocytes were detected by immunoblotting and ELISPOT, respectively. Protective abilities in mice provided by the vaccines were evaluated by residual virus titers in organs, survival rate and weight loss. RESULTS: These DNA vaccines, especially m04, M84 and IE-1, could effectively reduce the virus loads in salivary glands and spleens of mice, but they couldn't completely clear the residual virus. Survival rates of 100% in mice after a lethal dose of MCMV infection could be reached by more than one dose of M84 vaccine or two doses of m04 or IE-1 vaccine. Immunization with M55 or M105 DNA at four doses offered mice only 62.5% survival rate after the lethal challenge. CONCLUSIONS: The study demonstrated that DNA vaccines could effectively afford mice protection against infection with a highly virulent MCMV and that the protection offered by induced CD8+ T cell immunity might be superior to that by gB-specific antibodies. These results are valuable references for development and application of HCMV vaccines.

An adjuvanted inactivated murine cytomegalovirus (MCMV) vaccine induces potent and long-term protective immunity against a lethal challenge with virulent MCMV.

BACKGROUND: Human cytomegalovirus (HCMV) is a ubiquitous pathogen that causes serious problems in immunocompromised or immunologically immature hosts. Vaccination is the preferred approach for prevention of HCMV infection, but so far no approved HCMV vaccine is available. In this study, we assessed the immunogenicity and protective immunity of a formalin-inactivated murine cytomegalovirus vaccine (FI-MCMV) in a mouse model in combination with adjuvants MF59, alum, or chitosan. METHODS: Specific-pathogen-free BALB/c mice aged 6-8 weeks were immunized twice, 3 weeks apart, with various doses of FI-MCMV (0.25 µg, 1 µg, 4 µg) with or without adjuvant. Mice were challenged with a lethal dose (5 × LD50) of a more virulent mouse salivary gland-passaged MCMV 3 weeks after the second immunization. The protective immunity of the vaccine was evaluated by determining the survival rates, residual spleen and salivary gland viral loads, body weight changes, and serum anti-MCMV IgG titers. RESULTS: Immunization with FI-MCMV vaccine induced a high level of specific antibody response. Antigen sparing was achieved by the addition of an adjuvant, which significantly enhanced the humoral response to vaccine antigens with a wide range of doses. The level of live virus detected in the spleen on day 5 and in the salivary glands on day 21 after the lethal challenge was significantly lower in adjuvant-treated groups than in controls. Survival rates in adjuvant-treated groups also increased significantly. Furthermore, these protective immune responses were sustained for at least 6 months following immunization. CONCLUSIONS: These results show that inactivated MCMV vaccine is effective, and that the adjuvanted FI-MCMV vaccine provides more effective and longer-term protection than the adjuvant-free vaccine.

Strong anisotropic third-harmonic generation in layered violet phosphorus.

We demonstrate that layered violet phosphorus, an emerging 2D semiconductor, undergoes strong anisotropic third-harmonic generation (THG). Polarization dependence of in-plane THG presents a cruciate-flower-shaped curve. Through theoretical modeling of the in-plane THG response, done by considering crystalline symmetry of violet phosphorus, we successfully quantify four non-zero third-order nonlinear optical susceptibility tensor elements. From control experiments, the magnitude of third-order nonlinear optical susceptibility |χ3| is calculated to be about 4.0 × 10-19 m2 V-2, which is comparable to those of conventional 2D layered semiconductors. These results indicate that the layered violet phosphorus can serve as an ideal building block for nonlinear optical applications.

Synergistic effect of protein foams and polysaccharide on the invisible hemostasis of acellular dermal matrix sponges.

Efficient management of hemorrhage is vital for preventing hemorrhagic shock and safeguarding wounds against infection. Inspired by the traditional Chinese steamed bread-making process, which involves kneading, foaming, and steaming, we devised a hemostatic sponge by amalgamating an acellular dermal matrix gel, hydroxyethyl starch, and rice hydrolyzed protein. The integration of hydroxyethyl starch bolstered the sponge's mechanical and hemostatic attributes, while the inclusion of rice hydrolyzed protein, acting as a natural foaming agent, enhanced its porosity This augmentation facilitated rapid blood absorption, accelerated clot formation, and stimulated the clotting cascade. Experimental findings underscore the exceptional biocompatibility and physicochemical characteristics of the hemostatic sponge, positioning it on par with commercially available collagen hemostatic sponges for hemorrhage control. Mechanistically, the sponge fosters aggregation and activation of red blood cells and platelets, expediting coagulation kinetics both in vivo and in vitro. Notably, this hemostatic sponge activates the clotting cascade sans crosslinking agents, offering a premium yet cost-effective biomaterial with promising clinical applicability.

Hsc70 promotes anti-tumor immunity by targeting PD-L1 for lysosomal degradation.

Immune checkpoint inhibition targeting the PD-1/PD-L1 pathway has become a powerful clinical strategy for treating cancer, but its efficacy is complicated by various resistance mechanisms. One of the reasons for the resistance is the internalization and recycling of PD-L1 itself upon antibody binding. The inhibition of lysosome-mediated degradation of PD-L1 is critical for preserving the amount of PD-L1 recycling back to the cell membrane. In this study, we find that Hsc70 promotes PD-L1 degradation through the endosome-lysosome pathway and reduces PD-L1 recycling to the cell membrane. This effect is dependent on Hsc70-PD-L1 binding which inhibits the CMTM6-PD-L1 interaction. We further identify an Hsp90α/ß inhibitor, AUY-922, which induces Hsc70 expression and PD-L1 lysosomal degradation. Either Hsc70 overexpression or AUY-922 treatment can reduce PD-L1 expression, inhibit tumor growth and promote anti-tumor immunity in female mice; AUY-922 can further enhance the anti-tumor efficacy of anti-PD-L1 and anti-CTLA4 treatment. Our study elucidates a molecular mechanism of Hsc70-mediated PD-L1 lysosomal degradation and provides a target and therapeutic strategies for tumor immunotherapy.

Clinical characteristics, risk factors, and prognostic analyses of coronary small vessel disease: a retrospective cohort study of 986 patients.

BACKGROUND AND AIMS: Coronary small vessel disease (CSVD) is often associated with significant percutaneous coronary intervention (PCI) related complications, complex lesions, complex PCI, and poor long-term prognosis. We designed this retrospective study to clarify the characteristics, risk factors, and prognostic analyses of CSVD in Chinese populations. METHODS: A total of 986 patients who underwent coronary angiography and stent implantation at the First Affiliated Hospital of Zhejiang University School of Medicine were evaluated. Patients were grouped into CSVD or non-small vessel disease (non-CSVD) according to stent diameter. Clinical data, coronary angiography, and long-term follow-up were recorded. Multivariate logistic regression, the Kaplan-Meier method, Log-rank Test, and Cox regression model were used for statistical analysis. RESULTS: Alcohol consumption (OR = 0.420, 95% CI: 0.299-0.588, P < 0.001) was implicated as a negative CSVD correlation factor. CSVD was more likely to be associated with multi-vessel lesions (79.2% vs. 49.4%, P < 0.001), bifurcation lesions (24.0% vs. 12.4%, P < 0.001), chronic total obstruction lesions (29.5% vs. 9.4%, P < 0.001), and long lesions (55.2% vs. 35.7%, P < 0.001), which reduced the efficacy of revascularization (70.1% vs. 85.1%, P < 0.001). In the follow-ups, cardiac death (2.3% vs. 0.4%, P = 0.008), stroke (1.9% vs. 0.3%, P = 0.007), target lesion revascularization (5.8% vs. 2.9%, P = 0.029), target vessel revascularization (6.8% vs. 3.4%, P = 0.016), and non-target vessel revascularization (7.8% vs. 4.0%, P = 0.012) were all substantially higher in CSVD patients. Troponin I level (OR = 1.008, 95% CI: 1.004-1.012, P < 0.001), complete revascularization (OR = 0.292, 95% CI: 0.160-0.531, P < 0.001), and aspirin administration (OR = 0.041, 95% CI: 0.013-0.131, P < 0.001) were independent predictors of MACE events of all patients. CONCLUSION: Compared to non-CSVD, CSVD was associated with more complex lesions, had worse revascularization efficacy, and a poorer prognosis.