Intracoronary Versus Intravenous Low-Dose Tirofiban in Patients With ST-Elevation Myocardial Infarction: A Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: This meta-analysis aimed to evaluate the effects of intracoronary (IC) low-dose tirofiban versus intravenous (IV) administration on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: All published randomised controlled trials (RCTs) comparing the effects of IC low-dose tirofiban (a bolus of ≤10 ug/kg) versus IV administration in patients with STEMI were identified by searching PubMed, EMBASE, Cochrane Library, and ISI Web of Science from inception to June 2023, with no language restriction. The risk ratio (RR) with 95% confidence intervals (CI) and the weighted mean difference (WMD) with 95% CI were calculated. RESULTS: Eleven RCTs involving 1,802 patients were included. Compared with the IV group, IC low-dose tirofiban was associated with improved major adverse cardiac events rate (RR 0.595, 95% CI 0.442-0.802; p=0.001), left ventricular ejection fraction (WMD 1.982, 95% CI 0.565-3.398; p=0.006), thrombolysis in myocardial infarction (TIMI) flow grade (RR 1.065, 95% CI 1.004-1.131; p=0.037), and TIMI myocardial perfusion grade (RR 1.194, 95% CI 1.001-1.425; p=0.049). The two groups had no significant difference in bleeding events (RR 0.952, 95% CI 0.709-1.279; p=0.745). CONCLUSIONS: Intracoronary low-dose tirofiban administration may be a safe and effective alternative to IV administration in STEMI patients.

PEX3 promotes regenerative repair after myocardial injury in mice through facilitating plasma membrane localization of ITGB3.

The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3ß signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.

Impact Analysis of COVID-19 Pandemic on Hospital Reviews on Dianping Website in Shanghai, China: Empirical Study.

BACKGROUND: In the era of the internet, individuals have increasingly accustomed themselves to gathering necessary information and expressing their opinions on public web-based platforms. The health care sector is no exception, as these comments, to a certain extent, influence people's health care decisions. During the onset of the COVID-19 pandemic, how the medical experience of Chinese patients and their evaluations of hospitals have changed remains to be studied. Therefore, we plan to collect patient medical visit data from the internet to reflect the current status of medical relationships under specific circumstances. OBJECTIVE: This study aims to explore the differences in patient comments across various stages (during, before, and after) of the COVID-19 pandemic, as well as among different types of hospitals (children's hospitals, maternity hospitals, and tumor hospitals). Additionally, by leveraging ChatGPT (OpenAI), the study categorizes the elements of negative hospital evaluations. An analysis is conducted on the acquired data, and potential solutions that could improve patient satisfaction are proposed. This study is intended to assist hospital managers in providing a better experience for patients who are seeking care amid an emergent public health crisis. METHODS: Selecting the top 50 comprehensive hospitals nationwide and the top specialized hospitals (children's hospitals, tumor hospitals, and maternity hospitals), we collected patient reviews from these hospitals on the Dianping website. Using ChatGPT, we classified the content of negative reviews. Additionally, we conducted statistical analysis using SPSS (IBM Corp) to examine the scoring and composition of negative evaluations. RESULTS: A total of 30,317 pieces of effective comment information were collected from January 1, 2018, to August 15, 2023, including 7696 pieces of negative comment information. Manual inspection results indicated that ChatGPT had an accuracy rate of 92.05%. The F1-score was 0.914. The analysis of this data revealed a significant correlation between the comments and ratings received by hospitals during the pandemic. Overall, there was a significant increase in average comment scores during the outbreak (P<.001). Furthermore, there were notable differences in the composition of negative comments among different types of hospitals (P<.001). Children's hospitals received sensitive feedback regarding waiting times and treatment effectiveness, while patients at maternity hospitals showed a greater concern for the attitude of health care providers. Patients at tumor hospitals expressed a desire for timely examinations and treatments, especially during the pandemic period. CONCLUSIONS: The COVID-19 pandemic had some association with patient comment scores. There were variations in the scores and content of comments among different types of specialized hospitals. Using ChatGPT to analyze patient comment content represents an innovative approach for statistically assessing factors contributing to patient dissatisfaction. The findings of this study could provide valuable insights for hospital administrators to foster more harmonious physician-patient relationships and enhance hospital performance during public health emergencies.

Exosomal miR-130b-3p suppresses metastasis of non-small cell lung cancer cells by targeting DEPDC1 via TGF-ß signaling pathway.

Exosomal miRNAs have vital functions in mediating intercellular communication as well as tumor occurrence and development. Thus, our research was aimed at exploring the regulatory mechanisms of exosomal miR-130b-3p/DEP domain containing 1 (DEPDC1)/transforming growth factor-ß (TGF-ß) signaling pathway in non-small cell lung cancer (NSCLC). Here we indicated that exosomal miR-130b-3p expression decreased in the serum of NSCLC patients, and it was of significant diagnostic value. Moreover, elevated miR-130b-3p levels suppressed the proliferation and migration of NSCLC cells, and enhanced their apoptosis. Conversely, miR-130b-3p down-regulation led to an opposite effect. As the upstream of DEPDC1, miR-130b-3p directly bound to 3'UTR in DEPDC1 to regulate its expression. DEPDC1 levels affected the proliferation, migration, and apoptosis of NSCLC cells via TGF-ß signaling pathway. Exosomal miR-130b-3p was highly expressed in BEAS-2B cells, besides, BEAS-2B cells transferred exosomal miR-130b-3p to NSCLC cells. Finally, exosomal miR-130b-3p suppressed NSCLC cell growth and migration, promoted their apoptosis via TGF-ß signaling pathway by decreasing DEPDC1 expression, and suppressed epithelial-mesenchymal transition (EMT) in NSCLC cells. In conclusion, exosomal miR-130b-3p has the potential to be a predictive biomarker for NSCLC, thereby stimulating the exploration of diagnostic and therapeutic approaches targeting NSCLC.

Thoracoscopic pulmonary resection combined with real-time image-guided percutaneous ablation for multiple pulmonary nodules: a novel surgical approach and literature review.

Background: Due to the widespread use of computed tomography (CT) screening and advances in diagnostic techniques, an increasing number of patients with multiple pulmonary nodules are being detected and pathologically diagnosed as synchronous multiple primary lung cancers (sMPLC). It has become a new challenge to treat multiple pulmonary nodules and obtain a favorable prognosis while minimizing the perioperative risk for patients. The purpose of this study was to summarize the preliminary experience with a hybrid surgery combining pulmonary resection and ablation for the treatment of sMPLC and to discuss the feasibility of this novel procedure with a literature review. Methods: This is a retrospective non-randomized controlled study. From January 1, 2022 to July 1, 2023, four patients underwent hybrid surgery combining thoracoscopic pulmonary resection and percutaneous pulmonary ablation for multiple pulmonary nodules. Patients were followed up at 3, 6 and 12 months postoperatively and the last follow-up was on November 30, 2023. Clinical characteristics, perioperative outcomes, pulmonary function recovery and oncologic prognosis were recorded. Meanwhile we did a literature review of studies on hybridized pulmonary surgery for the treatment of multiple pulmonary nodules. Results: All the four patients were female, aged 52 to 70 years, and had no severe cardiopulmonary dysfunction on preoperative examination. Hybrid surgery of simultaneous pulmonary resection and ablation were performed in these patients to treat 2 to 4 pulmonary nodules, assisted by intraoperative real-time guide of C-arm X-ray machine. The operation time was from 155 to 240 minutes, and intraoperative blood loss was from 50 to 200 mL. Postoperative hospital stay was 2 to 7 days, thoracic drainage duration was 2 to 6 days, and pleural drainage volume was 300-1,770 mL. One patient presented with a bronchopleural fistula due to pulmonary ablation; the fistula was identified and sutured during thoracoscopic surgery and the patient recovered well. No postoperative 90-day complications occurred. After 3 months postoperatively, performance status scores for these patients recovered to 80 to 100. No tumor recurrence or metastasis was detected during the follow-up period. Conclusions: Hybrid procedures combining minimally invasive pulmonary resection with ablation are particularly suitable for the simultaneous treatment of sMPLC. Patients had less loss of pulmonary function, fewer perioperative complications, and favorable oncologic prognosis. Hybrid surgery is expected to be a better treatment option for patients with sMPLC.

NS2 induces an influenza A RNA polymerase hexamer and acts as a transcription to replication switch.

Genome transcription and replication of influenza A virus (FluA), catalyzed by viral RNA polymerase (FluAPol), are delicately controlled across the virus life cycle. A switch from transcription to replication occurring at later stage of an infection is critical for progeny virion production and viral non-structural protein NS2 has been implicated in regulating the switch. However, the underlying regulatory mechanisms and the structure of NS2 remained elusive for years. Here, we determine the cryo-EM structure of the FluAPol-NS2 complex at ~3.0 Å resolution. Surprisingly, three domain-swapped NS2 dimers arrange three symmetrical FluPol dimers into a highly ordered barrel-like hexamer. Further structural and functional analyses demonstrate that NS2 binding not only hampers the interaction between FluAPol and the Pol II CTD because of steric conflicts, but also impairs FluAPol transcriptase activity by stalling it in the replicase conformation. Moreover, this is the first visualization of the full-length NS2 structure. Our findings uncover key molecular mechanisms of the FluA transcription-replication switch and have implications for the development of antivirals.

Transoceanic ships as a source of alien dinoflagellate invasions of inland freshwater ecosystems.

Ships' ballast water and sediments have long been linked to the global transport and expansion of invasive species and thus have become a hot research topic and administrative challenge in the past decades. The relevant concerns, however, have been mainly about the ocean-to-ocean invasion and sampling practices have been almost exclusively conducted onboard. We examined and compared the dinoflagellate cysts assemblages in 49 sediment samples collected from ballast tanks of international and domestic routes ships, washing basins associated with a ship-repair yard, Jiangyin Port (PS), and the nearby area of Yangtze River (YR) during 2017-2018. A total of 43 dinoflagellates were fully identified to species level by metabarcoding, single-cyst PCR-based sequencing, cyst germination and phylogenetic analyses, including 12 species never reported from waters of China, 14 HABs-causing, 9 toxic, and 10 not strictly marine species. Our metabarcoding and single-cyst sequencing also detected many OTUs and cysts of dinoflagellates that could not be fully identified, indicating ballast tank sediments being a risky repository of currently unrecognizable invasive species. Particularly important, 10 brackish and fresh water species of dinoflagellate cysts (such as Tyrannodinium edax) were detected from the transoceanic ships, indicating these species may function as alien species potentially invading the inland rivers and adjacent lakes if these ships conduct deballast and other practices in fresh waterbodies. Significantly higher numbers of reads and OTUs of dinoflagellates in the ballast tanks and washing basins than that in PS and YR indicate a risk of releasing cysts by ships and the associated ship-repair yards to the surrounding waters. Phylogenetic analyses revealed high intra-species genetic diversity for multiple cyst species from different ballast tanks. Our work provides novel insights into the risk of bio-invasion to fresh waters conveyed in ship's ballast tank sediments and washing basins of shipyards.

Development of a novel PCV2 and PCV3 vaccine using virus-like vesicles incorporating Venezuelan equine encephalomyelitis virus-containing vesicular stomatitis virus glycoprotein.

Porcine circovirus disease (PCV) causes substantial economic losses in the pig industry, primarily from porcine circovirus type 2 (PCV2) and porcine circovirus type 3 (PCV3). Novel vaccines are necessary to prevent and control PCV infections. PCV coat proteins are crucial for eliciting immunogenic proteins that induce the production of antibodies and immune responses. A vaccine platform utilizing Semliki Forest virus RNA replicons expressing vesicular stomatitis virus glycoprotein (VSV-G), was recently developed. This platform generates virus-like vesicles (VLVs) containing VSV-G exclusively, excluding other viral structural proteins. In our study, we developed a novel virus-like vesicle vaccine by constructing recombinant virus-like vesicles (rVLVs) that also express EGFP. These rVLVs were created using the RNA replicon of Venezuelan equine encephalomyelitis (VEEV) and New Jersey serotype VSV-G. The rVLVs underwent characterization and safety evaluation in vitro. Subsequently, rVLVs expressing PCV2d-Cap and PCV3-Cap proteins were constructed. Immunization of C57 mice with these rVLVs led to a significant increase in anti-porcine circovirus type 2 and type 3 capsid protein antibodies in mouse serum. Additionally, a cellular immune response was induced, as evidenced by high production of IFN-γ and IL-4 cytokines. Overall, this study demonstrates the feasibility of developing a novel porcine circovirus disease vaccine based on rVLVs.

Nutrient deficiency patterns and all-cause and cardiovascular mortality in older adults with hypertension: a latent class analysis.

BACKGROUND: Previous researches examining the impact of dietary nutrition on mortality risk have mainly focused on individual nutrients, however the interaction of these nutrients has not been considered. The purpose of this study was to identify of nutrient deficiencies patterns and analyze their potential impact on mortality risk in older adults with hypertension. METHODS: We included participants from the National Health and Nutrition Examination Survey (NHANES) study. The latent class analysis (LCA) was applied to uncover specific malnutrition profiles within the sample. Risk of the end points across the phenogroups was compared using Kaplan-Meier analysis and Cox proportional hazard regression model. Multinomial logistic regression was used to determine the influencing factors of specific malnutrition profiles. RESULTS: A total of 6924 participants aged 60 years or older with hypertension from NHANES 2003-2014 was followed until December 31, 2019 with a median follow-up of 8.7 years. Various nutrients included vitamin A, vitamin B1, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, fiber, folate, calcium, magnesium, zinc, copper, iron, and selenium, and LCA revealed 4 classes of malnutrition. Regarding all-cause mortality, "Nutrient Deprived" group showed the strongest hazard ratio (1.42 from 1.19 to 1.70) compared with "Adequate Nutrient" group, followed by "Inadequate Nutrient" group (1.29 from 1.10 to 1.50), and "Low Fiber, Magnesium, and Vit E" group (1.17 from 1.02 to 1.35). For cardiovascular mortality, "Nutrient Deprived" group showed the strongest hazard ratio (1.61 from 1.19 to 2.16) compared with "Adequate Nutrient" group, followed by "Low Fiber, Magnesium, and Vit E" group (1.51 from 1.04 to 2.20), and "Inadequate Nutrient" group (1.37 from 1.03 to 1.83). CONCLUSIONS: The study revealed a significant association between nutrients deficiency patterns and the risk of all-cause and cardiovascular mortality in older adults with hypertension. The findings suggested that nutrients deficiency pattern may be an important risk factor for mortality in older adults with hypertension.

Atomic Layer Deposition of TiO2 on Si Window Enables In Situ ATR-SEIRAS Measurements in Strong Alkaline Electrolytes.

The Si window is the most widely used internal reflection element (IRE) for electrochemical attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS), yet local chemical etching on Si by concentrated OH- anions bottlenecks the reliable application of this method in strong alkaline electrolytes. In this report, atomic layer deposition of a 25 nm nonconductive TiO2 barrier layer on the reflecting plane of a Si prism is demonstrated to address this challenge. In situ ATR-SEIRAS measurement on a Au film electrode with the Si/TiO2 composite IRE in 1 M NaOH reveals reversible global spectral features without spectral distortion at 1000-1300 cm-1, in stark contrast to those obtained with a bare Si window. By applying this structured ATR-SEIRAS, ethanol electrooxidation on a Pt/C catalyst in 1 and 5 M NaOH is explored, manifesting that such high pH values prevent the adsorption of as-formed acetate in the C2 pathway but not that of CO intermediate in the C1 pathway.

Adipocyte secreted NRG4 ameliorates age-associated metabolic dysfunction.

With the progressive aging of society, there is an increasing prevalence of age-related diseases that pose a threat to the elderly's quality of life. Adipose tissue, a vital energy reservoir with endocrine functions, is one of the most vulnerable tissues in aging, which in turn influences systematic aging process, including metabolic dysfunction. However, the underlying mechanism is still poorly understood. In this study, we found that NRG4, a novel adipokine, is obviously decreased in adipocyte tissues and serums during aging. Moreover, delivered recombinant NRG4 protein (rNRG4) into aged mice can ameliorate age-associated insulin resistance, glucose disorders and other metabolic disfunction. In addition, rNRG4 treatment alleviates age-associated hepatic steatosis and sarcopenia, accompanied with altered gene signatures. Together, these results indicate that NRG4 plays a key role in the aging process and is a therapeutic target for the treatment of age-associated metabolic dysfunction.

Effect of endoscopic full-thickness resection assisted by distal serosal turnover with floss traction for gastric submucosal masses.

BACKGROUND: Complex and high-risk surgical complications pose pressing challenges in the clinical implementation and advancement of endoscopic full-thickness resection (EFTR). Successful perforation repair under endoscopy, thereby avoiding surgical intervention and postoperative complications such as peritonitis, are pivotal for effective EFTR. AIM: To investigate the effectiveness and safety of EFTR assisted by distal serosal inversion under floss traction in gastric submucosal tumors. METHODS: A retrospective analysis of patients with gastric and duodenal submucosal tumors treated with EFTR assisted by the distal serosa inversion under dental floss traction from January 2023 to January 2024 was conducted. The total operation time, tumor dissection time, wound closure time, intraoperative bleeding volume, length of hospital stay and incidence of complications were analyzed. RESULTS: There were 93 patients, aged 55.1 ± 12.1 years. Complete tumor resection was achieved in all cases, resulting in a 100% success rate. The average total operation time was 67.4 ± 27.0 min, with tumor dissection taking 43.6 ± 20.4 min. Wound closure times varied, with gastric body closure time of 24.5 ± 14.1 min and gastric fundus closure time of 16.6 ± 8.7 min, showing a significant difference (P < 0.05). Intraoperative blood loss was 2.3 ± 4.0 mL, and average length of hospital stay was 5.7 ± 1.9 d. There was no secondary perforation after suturing in all cases. The incidence of delayed bleeding was 2.2%, and the incidence of abdominal infection was 3.2%. No patient required other surgical intervention during and after the operation. CONCLUSION: Distal serosal inversion under dental-floss-assisted EFTR significantly reduced wound closure time and intraoperative blood loss, making it a viable approach for gastric submucosal tumors.

Checkpoint Kinase 1 Stimulates Endogenous Cardiomyocyte Renewal and Cardiac Repair by Binding to Pyruvate Kinase Isoform M2 C-Domain and Activating Cardiac Metabolic Reprogramming in a Porcine Model of Myocardial Ischemia/Reperfusion Injury.

BACKGROUND: The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell-cycle withdrawal. This translational study evaluated the effects and underlying mechanism of rhCHK1 (recombinant human checkpoint kinase 1) on the survival and proliferation of cardiomyocyte and myocardial repair after ischemia/reperfusion injury in swine. METHODS AND RESULTS: Intramyocardial injection of rhCHK1 protein (1 mg/kg) encapsulated in hydrogel stimulated cardiomyocyte proliferation and reduced cardiac inflammation response at 3 days after ischemia/reperfusion injury, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after ischemia/reperfusion injury. Mechanistically, multiomics sequencing analysis demonstrated enrichment of glycolysis and mTOR (mammalian target of rapamycin) pathways after rhCHK1 treatment. Co-Immunoprecipitation (Co-IP) experiments and protein docking prediction showed that CHK1 (checkpoint kinase 1) directly bound to and activated the Serine 37 (S37) and Tyrosine 105 (Y105) sites of PKM2 (pyruvate kinase isoform M2) to promote metabolic reprogramming. We further constructed plasmids that knocked out different CHK1 and PKM2 amino acid domains and transfected them into Human Embryonic Kidney 293T (HEK293T) cells for CO-IP experiments. Results showed that the 1-265 domain of CHK1 directly binds to the 157-400 amino acids of PKM2. Furthermore, hiPSC-CM (human iPS cell-derived cardiomyocyte) in vitro and in vivo experiments both demonstrated that CHK1 stimulated cardiomyocytes renewal and cardiac repair by activating PKM2 C-domain-mediated cardiac metabolic reprogramming. CONCLUSIONS: This study demonstrates that the 1-265 amino acid domain of CHK1 binds to the 157-400 domain of PKM2 and activates PKM2-mediated metabolic reprogramming to promote cardiomyocyte proliferation and myocardial repair after ischemia/reperfusion injury in adult pigs.

Chromosome-level genome assemblies of Musa ornata and Musa velutina provide insights into pericarp dehiscence and anthocyanin biosynthesis in banana.

Musa ornata and Musa velutina are members of the Musaceae family and are indigenous to the South and Southeast Asia. They are very popular in the horticultural market, but the lack of genomic sequencing data and genetic studies has hampered efforts to improve their ornamental value. In this study, we generated the first chromosome-level genome assemblies for both species by utilizing Oxford Nanopore long reads and Hi-C reads. The genomes of M. ornata and M. velutina were assembled into 11 pseudochromosomes with genome sizes of 427.85 Mb and 478.10 Mb, respectively. Repetitive sequences comprised 46.70% and 50.91% of the total genomes for M. ornata and M. velutina, respectively. Differentially expressed gene (DEG) and Gene Ontology (GO) enrichment analyses indicated that upregulated genes in the mature pericarps of M. velutina were mainly associated with the saccharide metabolic processes, particularly at the cell wall and extracellular region. Furthermore, we identified polygalacturonase (PG) genes that exhibited higher expression level in mature pericarps of M. velutina compared to other tissues, potentially being accountable for pericarp dehiscence. This study also identified genes associated with anthocyanin biosynthesis pathway. Taken together, the chromosomal-level genome assemblies of M. ornata and M. velutina provide valuable insights into the mechanism of pericarp dehiscence and anthocyanin biosynthesis in banana, which will significantly contribute to future genetic and molecular breeding efforts.

Testing plastomes and nuclear ribosomal DNA sequences as the next-generation DNA barcodes for species identification and phylogenetic analysis in Acer.

BACKGROUND: Acer is a taxonomically intractable and speciose genus that contains over 150 species. It is challenging to distinguish Acer species only by morphological method due to their abundant variations. Plastome and nuclear ribosomal DNA (nrDNA) sequences are recommended as powerful next-generation DNA barcodes for species discrimination. However, their efficacies were still poorly studied. The current study will evaluate the application of plastome and nrDNA in species identification and perform phylogenetic analyses for Acer. RESULT: Based on a collection of 83 individuals representing 55 species (c. 55% of Chinese species) from 13 sections, our barcoding analyses demonstrated that plastomes exhibited the highest (90.47%) species discriminatory power among all plastid DNA markers, such as the standard plastid barcodes matK + rbcL + trnH-psbA (61.90%) and ycf1 (76.19%). And the nrDNA (80.95%) revealed higher species resolution than ITS (71.43%). Acer plastomes show abundant interspecific variations, however, species identification failure may be due to the incomplete lineage sorting (ILS) and chloroplast capture resulting from hybridization. We found that the usage of nrDNA contributed to identifying those species that were unidentified by plastomes, implying its capability to some extent to mitigate the impact of hybridization and ILS on species discrimination. However, combining plastome and nrDNA is not recommended given the cytonuclear conflict caused by potential hybridization. Our phylogenetic analysis covering 19 sections (95% sections of Acer) and 128 species (over 80% species of this genus) revealed pervasive inter- and intra-section cytonuclear discordances, hinting that hybridization has played an important role in the evolution of Acer. CONCLUSION: Plastomes and nrDNA can significantly improve the species resolution in Acer. Our phylogenetic analysis uncovered the scope and depth of cytonuclear conflict in Acer, providing important insights into its evolution.

Manipulating 2D Membrane Interlayer Channels with Accelerated Mass-Transfer Behavior to Boost Solar Desalination.

The scarcity of fresh water necessitates sustainable and efficient water desalination strategies. Solar-driven steam generation (SSG), which employs solar energy for water evaporation, has emerged as a promising approach. Graphene oxide (GO)-based membranes possess advantages like capillary action and Marangoni effect, but their stacking defects and dead zones of flexible flakes hinders efficient water transportation, thus the evaporation rate lag behind unobstructed-porous 3D evaporators. Therefore, fundamental mass-transfer approach for optimizing SSG evaporators offers new horizons. Herein, a universal multi-force-fields-based method is presented to regularize membrane channels, which can mechanically eliminate inherent interlayer stackings and defects. Both characterization and simulation demonstrate the effectiveness of this approach across different scales and explain the intrinsic mechanism of mass-transfer enhancement. When combined with a structurally optimized substrate, the 4Laponite@GO-1 achieves evaporation rate of 2.782 kg m-2 h-1 with 94.48% evaporation efficiency, which is comparable with most 3D evaporators. Moreover, the optimized membrane exhibits excellent cycling stability (10 days) and tolerance to extreme conditions (pH 1-14, salinity 1%-15%), verifies the robust structural stability of regularized channels. This optimization strategy provides simple but efficient way to enhance the SSG performance of GO-based membranes, facilitating their extensive application in sustainable water purification technologies.

Extension and Fusion of Cyclic Polyantimony Units.

The synthesis and characterization of a series of polyantimony anionic clusters are reported. The products [(NbCp)2Sb10]2-, [MSb13]3- (M = Ru/Fe), and [MSb15]3- (M = Ru/Fe) were isolated as either K(18-crown-6) or K([2.2.2]-crypt) salts. The Sb10 ring contained in the [(NbCp)2Sb10]2- cluster can be viewed as an extension of two envelope-like cyclo-Sb5 units and represents by far the largest monocyclic all-antimony species. The clusters [MSb13]3- and [MSb15]3- (M = Ru/Fe) illustrate the variability of crown-like Sb8 ring motifs and reveal the fusion of different antimony fragments featuring unique Sb-Sb chain-like units. The reported synthetic approaches involve the fabrication of a variety of distinctive polyantimony anionic clusters, enhancing our understanding of the coordination chemistry of heavier group 15 elements.

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.

Calmodulin-like 5 promotes PEDV replication by regulating late-endosome synthesis and innate immune response.

The infection caused by porcine epidemic diarrhea virus (PEDV) is associated with high mortality in piglets worldwide. Host factors involved in the efficient replication of PEDV, however, remain largely unknown. Our recent proteomic study in the virus-host interaction network revealed a significant increase in the accumulation of CALML5 (EF-hand protein calmodulin-like 5) following PEDV infection. A further study unveiled a biphasic increase of CALML5 in 2 and 12 â€‹h after viral infection. Similar trends were observed in the intestines of piglets in the early and late stages of the PEDV challenge. Moreover, CALML5 depletion reduced PEDV mRNA and protein levels, leading to a one-order-of-magnitude decrease in virus titer. At the early stage of PEDV infection, CALML5 affected the endosomal trafficking pathway by regulating the expression of endosomal sorting complex related cellular proteins. CALML5 depletion also suppressed IFN-ß and IL-6 production in the PEDV-infected cells, thereby indicating its involvement in negatively regulating the innate immune response. Our study reveals the biological function of CALML5 in the virology field and offers new insights into the PEDV-host cell interaction.

Functional dissection of parabrachial substrates in processing nociceptive information.

Painful stimuli elicit first-line reflexive defensive reactions and, in many cases, also evoke second-line recuperative behaviors, the latter of which reflects the sensing of tissue damage and the alleviation of suffering. The lateral parabrachial nucleus (lPBN), composed of external- (elPBN), dorsal- (dlPBN), and central/superior-subnuclei (jointly referred to as slPBN), receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption. However, the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear. In this study, we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor ( NK1R) (lPBN NK1R) are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle, while elPBN neurons are dispensable for driving such reactions. Notably, lPBN NK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats. Lastly, both lPBN NK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions. Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.