Genomic Insights into the First Emergence of blaNDM-5-Carrying Carbapenem-Resistant Salmonella enterica Serovar London Strain in China.

Carbapenem-resistant Salmonella enterica (S. enterica) pose a significant threat to public health, causing gastroenteritis and invasive infections. We report the first emergence of a carbapenem-resistant S. enterica serovar London strain, A132, carrying the blaNDM-5 gene in China. Whole-genome sequencing and bioinformatics analysis assigned A132 to be ST155, a multidrug-resistant clone frequently reported in China. The strain A132 exhibited resistance to multiple antibiotics, with 20 acquired antibiotic resistance genes (ARGs) identified, predominantly located on the IncFIB plasmid (pA132-1-NDM). Notably, the blaNDM-5 gene was located within an IS26 flanked-class 1 integron-ISCR1 complex, comprising two genetic cassettes. One cassette is the class 1 integron, which may facilitate the transmission of the entire complex, while the other is the blaNDM-5-containing ISCR1-IS26-flanked cassette, carrying multiple other ARGs. Genbank database search based on the blaNDM-5-carrying cassette identified a similar genetic context found in transmissible IncFIA plasmids from Escherichia coli (p91) and Enterobacter hormaechei (p388) with a shared host range, suggesting the potential for cross-species transmission of blaNDM-5. To our knowledge, this is the first reported case of Salmonella serovar London ST155 harboring blaNDM-5 gene. Phylogenetic analysis indicated a close relationship between A132 and eight S. London ST155 strains isolated from the same province. However, A132 differed by carrying the blaNDM-5 gene and four unique ARGs. Given the high transmissibility of the F-type plasmid harboring blaNDM-5 and 18 other ARGs, it is imperative to implement vigilant surveillance and adopt appropriate infection control measures to mitigate the threat to public health.

Great genetic diversity of vector-borne bacteria and protozoan in wild rodents from Guangxi, China.

BACKGROUND: Rodents are recognized as the hosts of many vector-borne bacteria and protozoan parasites and play an important role in their transmission and maintenance. Intensive studies have focused on their infections in vectors, especially in ticks, however, vector-borne bacterial and protozoan infections in rodents are poorly understood although human cases presenting with fever may due to their infection have been found. METHODS: From May to October 2019, 192 wild rodents were trapped in wild environment of Guangxi Province, and the spleen samples were collected to reveal the presence of vector-borne bacterial and protozoan infections in them. The microorganisms in rodents were identified by detecting their DNA using (semi-)nested PCR. All the PCR products of the expected size were subjected to sequencing, and then analyzed by BLASTn. Furthermore, all the recovered sequences were subjected to nucleotide identity and phylogenetic analyses. RESULTS: As a result, 192 rodents representing seven species were captured, and Bandicota indica were the dominant species, followed by Rattus andamanensis. Based on the (semi-)nested PCR, our results suggested that Anaplasma bovis, Anaplasma capra, Anaplasma ovis, Anaplasma phagocytophilum, "Candidatus Neoehrlichia mikurensis", "Candidatus E. hainanensis", "Candidatus E. zunyiensis", three uncultured Ehrlichia spp., Bartonella coopersplainsensis, Bartonella tribocorum, Bartonella rattimassiliensis, Bartonella silvatica, two uncultured Bartonella spp., Babesia microti and diverse Hepatozoon were identified in six rodent species. More importantly, six species (including two Anaplasma, two Bartonella, "Ca. N. mikurensis" and Bab. microti) are zoonotic pathogens except Anaplasma bovis and Anaplasma ovis with zoonotic potential. Furthermore, dual infection was observed between different microorganisms, and the most common type of co-infection is between "Ca. N. mikurensis" and other microorganisms. Additionally, potential novel Bartonella species and Hepatozoon species demonstrated the presence of more diverse rodent-associated Bartonella and Hepatozoon. CONCLUSIONS: The results in this work indicated great genetic diversity of vector-borne infections in wild rodents, and highlighted the potential risk of human pathogens transmitted from rodents to humans through vectors.

Surface property and in vitro toxicity effect of insoluble particles given by protein corona: Implication for PM cytotoxicity assessment.

In vitro toxicological assessment helps explore key fractions of particulate matter (PM) in association with the toxic mechanism. Previous studies mainly discussed the toxicity effects of the water-soluble and organic-soluble fractions of PM. However, the toxicity of insoluble fractions is relatively poorly understood, and the adsorption of proteins is rarely considered. In this work, the formation of protein corona on the surface of insoluble particles during incubation in a culture medium was investigated. It was found that highly abundant proteins in fetal bovine serum were the main components of the protein corona. The adsorbed proteins increased the dispersion stability of insoluble particles. Meanwhile, the leaching concentrations of some metal elements (e.g., Cu, Zn, and Pb) from PM increased in the presence of proteins. The toxicity effects and potential mechanisms of the PM insoluble particle-protein corona complex on macrophage cells RAW264.7 were discussed. The results revealed that the PM insoluble particle-protein corona complex could influence the phagosome pathway in RAW264.7 cells. Thus, it promoted the intracellular reactive oxygen species generation and induced a greater degree of cell differentiation, significantly altering cell morphology. Consequently, this work sheds new light on the combination of insoluble particles and protein corona in terms of PM cytotoxicity assessment.

FBXO32-mediated degradation of PTEN promotes lung adenocarcinoma progression.

FBXO32, a member of the F-box protein family, is known to play both oncogenic and tumor-suppressive roles in different cancers. However, the functions and the molecular mechanisms regulated by FBXO32 in lung adenocarcinoma (LUAD) remain unclear. Here, we report that FBXO32 is overexpressed in LUAD compared with normal lung tissues, and high expression of FBXO32 correlates with poor prognosis in LUAD patients. Firstly, we observed with a series of functional experiments that FBXO32 alters the cell cycle and promotes the invasion and metastasis of LUAD cells. We further corroborate our findings using in vivo mouse models of metastasis and confirmed that FBXO32 positively regulates LUAD tumor metastasis. Using a proteomic-based approach combined with computational analyses, we found a positive correlation between FBXO32 and the PI3K/AKT/mTOR pathway, and identified PTEN as a FBXO32 interactor. More important, FBXO32 binds PTEN via its C-terminal substrate binding domain and we also validated PTEN as a bona fide FBXO32 substrate. Finally, we demonstrated that FBXO32 promotes EMT and regulates the cell cycle by targeting PTEN for proteasomal-dependent degradation. In summary, our study highlights the role of FBXO32 in promoting the PI3K/AKT/mTOR pathway via PTEN degradation, thereby fostering lung adenocarcinoma progression.

Dysregulated Ribosome Biogenesis Is a Targetable Vulnerability in Triple-Negative Breast Cancer: MRPS27 as a Key Mediator of the Stemness-inhibitory Effect of Lovastatin.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with limited effective therapeutic options readily available. We have previously demonstrated that lovastatin, an FDA-approved lipid-lowering drug, selectively inhibits the stemness properties of TNBC. However, the intracellular targets of lovastatin in TNBC remain largely unknown. Here, we unexpectedly uncovered ribosome biogenesis as the predominant pathway targeted by lovastatin in TNBC. Lovastatin induced the translocation of ribosome biogenesis-related proteins including nucleophosmin (NPM), nucleolar and coiled-body phosphoprotein 1 (NOLC1), and the ribosomal protein RPL3. Lovastatin also suppressed the transcript levels of rRNAs and increased the nuclear protein level and transcriptional activity of p53, a master mediator of nucleolar stress. A prognostic model generated from 10 ribosome biogenesis-related genes showed outstanding performance in predicting the survival of TNBC patients. Mitochondrial ribosomal protein S27 (MRPS27), the top-ranked risky model gene, was highly expressed and correlated with tumor stage and lymph node involvement in TNBC. Mechanistically, MRPS27 knockdown inhibited the stemness properties and the malignant phenotypes of TNBC. Overexpression of MRPS27 attenuated the stemness-inhibitory effect of lovastatin in TNBC cells. Our findings reveal that dysregulated ribosome biogenesis is a targetable vulnerability and targeting MRPS27 could be a novel therapeutic strategy for TNBC patients.

ABCG2-Expressing Clonal Repopulating Endothelial Cells Serve to Form and Maintain Blood Vessels.

BACKGROUND: Most organs are maintained lifelong by resident stem/progenitor cells. During development and regeneration, lineage-specific stem/progenitor cells can contribute to the growth or maintenance of different organs, whereas fully differentiated mature cells have less regenerative potential. However, it is unclear whether vascular endothelial cells (ECs) are also replenished by stem/progenitor cells with EC-repopulating potential residing in blood vessels. It has been reported recently that some EC populations possess higher clonal proliferative potential and vessel-forming capacity compared with mature ECs. Nevertheless, a marker to identify vascular clonal repopulating ECs (CRECs) in murine and human individuals is lacking, and, hence, the mechanism for the proliferative, self-renewal, and vessel-forming potential of CRECs is elusive. METHODS: We analyzed colony-forming, self-renewal, and vessel-forming potential of ABCG2 (ATP binding cassette subfamily G member 2)-expressing ECs in human umbilical vessels. To study the contribution of Abcg2-expressing ECs to vessel development and regeneration, we developed Abcg2CreErt2;ROSA TdTomato mice and performed lineage tracing during mouse development and during tissue regeneration after myocardial infarction injury. RNA sequencing and chromatin methylation chromatin immunoprecipitation followed by sequencing were conducted to study the gene regulation in Abcg2-expressing ECs. RESULTS: In human and mouse vessels, ECs with higher ABCG2 expression (ABCECs) possess higher clonal proliferative potential and in vivo vessel-forming potential compared with mature ECs. These cells could clonally contribute to vessel formation in primary and secondary recipients after transplantation. These features of ABCECs meet the criteria of CRECs. Results from lineage tracing experiments confirm that Abcg2-expressing CRECs (AbcCRECs) contribute to arteries, veins, and capillaries in cardiac tissue development and vascular tissue regeneration after myocardial infarction. Transcriptome and epigenetic analyses reveal that a gene expression signature involved in angiogenesis and vessel development is enriched in AbcCRECs. In addition, various angiogenic genes, such as Notch2 and Hey2, are bivalently modified by trimethylation at the 4th and 27th lysine residue of histone H3 (H3K4me3 and H3K27me3) in AbcCRECs. CONCLUSIONS: These results are the first to establish that a single prospective marker identifies CRECs in mice and human individuals, which holds promise to provide new cell therapies for repair of damaged vessels in patients with endothelial dysfunction.

Anaplasma, Bartonella, and Rickettsia infections in Daurian ground squirrels (Spermophilus dauricus), Hebei, China.

Rodents have been confirmed as hosts of various vector-borne zoonotic pathogens and are important for the maintenance of these microbes in nature. However, surveillance for zoonotic pathogens is limited for many wild rodent species in China, so our knowledge of pathogen ecology, genetic diversity, and the risk of cross-species transmission to humans is limited. In this study, 165 spleen samples of Daurian ground squirrels (Spermophilus dauricus) were collected from Weichang Manchu and the Mongolian Autonomous County of Hebei Province, China, and Rickettsia, Bartonella, and Anaplasma were identified by DNA detection using polymerase chain reaction (PCR). Sequence analysis identified eight bacterial pathogens: R. raoultii, R. sibirica, Candidatus R. longicornii, B. washoensis, B. grahamii, B. jaculi, A. capra, and Candidatus Anaplasma cinensis. Co-infection of B. grahamii and R. raoultii in one sample was observed. Our results demonstrated the genetic diversity of bacteria in Daurian ground squirrels and contributed to the distribution of these pathogens. Six species, A. capra, R. raoultii, R. sibirica, Candidatus R. longicornii, B. washoensis, and B. grahamii, are known to be pathogenic to humans, indicating a potential public health risk to the local human population, especially to herders who frequently have close contact with Daurian ground squirrels and are thus exposed to their ectoparasites.

Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cells.

PURPOSE: Radiotherapy (RT) is the primary treatment for prostate cancer (PCa); however, the emergence of castration-resistant prostate cancer (CRPC) often leads to treatment failure and cancer-related deaths. In this study, we aimed to explore the use of microwave hyperthermia (MW-HT) to sensitize PCa to RT and investigate the underlying molecular mechanisms. METHODS: We developed a dedicated MW-HT heating setup, created an in vitro and in vivo MW-HT + RT treatment model for CRPC. We evaluated PC3 cell proliferation using CCK-8, colony experiments, DAPI staining, comet assay and ROS detection method. We also monitored nude mouse models of PCa during treatment, measured tumor weight, and calculated the tumor inhibition rate. Western blotting was used to detect DNA damage repair protein expression in PC3 cells and transplanted tumors. RESULTS: Compared to control, PC3 cell survival and clone formation rates decreased in RT + MW-HT group, demonstrating significant increase in apoptosis, ROS levels, and DNA damage. Lower tumor volumes and weights were observed in treatment groups. Ki-67 expression level was reduced in all treatment groups, with significant decrease in RT + MW-HT groups. The most significant apoptosis induction was confirmed in RT + MW-HT group by TUNEL staining. Protein expression levels of DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways significantly decreased in RT + MW-HT groups. CONCLUSION: MW-HT + RT treatment significantly inhibited DNA damage repair by downregulating DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways, leading to increased ROS levels, aggravate DNA damage, apoptosis, and necrosis in PC3 cells, a well-established model of CRPC.

Mechanical Unloading Promotes Osteoclastic Differentiation and Bone Resorption by Modulating the MSC Secretome to Favor Inflammation.

Aging, space flight, and prolonged bed rest have all been linked to bone loss, and no effective treatments are clinically available at present. Here, with the rodent hindlimb unloading (HU) model, we report that the bone marrow (BM) microenvironment was significantly altered, with an increased number of myeloid cells and elevated inflammatory cytokines. In such inflammatory BM, the osteoclast-mediated bone resorption was greatly enhanced, leading to a shifted bone remodeling balance that ultimately ends up with disuse-induced osteoporosis. Using Piezo1 conditional knockout (KO) mice (Piezo1fl/fl;LepRCre), we proved that lack of mechanical stimuli on LepR+ mesenchymal stem cells (MSCs) is the main reason for the pathological BM inflammation. Mechanically, the secretome of MSCs was regulated by mechanical stimuli. Inadequate mechanical load leads to increased production of inflammatory cytokines, such as interleukin (IL)-1α, IL-6, macrophage colony-stimulating factor 1 (M-CSF-1), and so on, which promotes monocyte proliferation and osteoclastic differentiation. Interestingly, transplantation of 10% cyclic mechanical stretch (CMS)-treated MSCs into HU animals significantly alleviated the BM microenvironment and rebalanced bone remodeling. In summary, our research revealed a new mechanism underlying mechanical unloading-induced bone loss and suggested a novel stem cell-based therapy to potentially prevent disuse-induced osteoporosis.

Genetic diversity of vector-borne zoonotic pathogens in companion dogs and cats, Tianjin, China.

Background: Dogs and cats are the hosts of many vector-borne human pathogens that can be transmitted to humans. Given their direct and intimate contact with humans, companion dogs and cats are considered direct sentinels of vector-borne human pathogens. However, limited information is currently available regarding canine and feline zoonotic pathogens in China. This study detected canine and feline vector-borne human pathogens to better understand the potential risk to humans. Methods: Blood samples were collected from 275 domestic companion animals (117 dogs and 158 cats) living in Tianjin city, China, and the presence of DNA from Anaplasma, Babesia, Bartonella, and Rickettsia was detected by semi-nested polymerase chain reaction (PCR). The PCR products of the expected size were sequenced, and these newly generated sequences were subjected to BLASTN, nucleotide identity, and phylogenetic analyses. Results: A total of 24 blood samples tested positive for vector-borne pathogens in companion dogs and cats in Tianjin city, China, with a relatively low positive rate of 8.7%. Specifically, seven human pathogens, including Rickettsia raoultii, Candidatus Rickettsia jingxinensis, Rickettsia sibirica, Rickettsia felis, Babesia venatorum, Bartonella tribocorum, and Bartonella Henselae, were identified. In addition, Anaplasma ovis with zoonotic potential and Candidatus A. cinensis were detected. Conclusion: Our results indicate substantial genetic diversity in the vector-borne human pathogens circulating in companion dogs and cats. Interventions based on "One Health" should be taken to reduce the potential risks of contracting infection from companion dogs and cats in Tianjin, China.

Identification of a Novel Peptide with Alcohol Dehydrogenase Activating Ability from Ethanol-Induced Lactococcus lactis: A Combined In Silico Prediction and In Vivo Validation.

Alcohol dehydrogenase (ADH) is a crucial rate-limiting enzyme in alcohol metabolism. Our previous research found that ethanol-induced intracellular extracts of Lactococcus lactis (L. lactis) could enhance alcohol metabolism in mice, but the responsible compounds remain unidentified. The study aimed to screen potential ADH-activating peptides from ethanol-induced L. lactis using virtual screening and molecular docking calculation. Among them, the pentapeptide FAPEG might bind to ADH through hydrophobic interaction and hydrogen bonds, then enhancing ADH activity. Spectroscopy analysis further investigated the peptide-enzyme interaction between FAPEG and ADH, including changes in the amino acid residue microenvironment and secondary structural alterations. Furthermore, FAPEG could protect against alcoholic liver injury (ALI) in mice by reducing blood alcohol concentration, enhancing the activity of antioxidant and alcohol metabolism enzymes, and attenuating alcohol-induced hepatotoxicity, which was related to the activation of the Nrf2/keap1/HO-1 signaling pathway. The study provided preliminary evidence that the generation of ADH-activating peptides in ethanol-induced L. lactis has the potential in preventing ALI in mice using in silico prediction and in vivo validation approaches.

Trifluoperazine regulates blood-brain barrier permeability via the MLCK/p-MLC pathway to promote ischemic stroke recovery.

Blood-brain barrier (BBB) disruption following ischemic stroke (IS) can induce significant aftereffects. Elevated calmodulin (CaM) expression following stroke causes calcium overload-a key contributor to BBB collapse. Trifluoperazine (TFP), a CaM inhibitor, reduces CaM overexpression following IS. However, it remains unclear whether TFP participates in BBB repair after IS. We administered TFP to mice subjected to middle cerebral artery occlusion (MCAO) and bEnd.3 cells subjected to oxygen-glucose deprivation (OGD). TFP treatment in MCAO mice reduced cerebral CaM expression and infarct size and decreased BBB permeability. OGD-treated bEnd.3 cells showed significantly increased CaM protein levels and reduced tight junction (TJ) protein levels; these changes were reversed by TFP treatment. Our results found that TFP administration in mice inhibited actin contraction following cerebral ischemia-reperfusion by suppressing the MLCK/p-MLC pathway, thereby attenuating cell retraction, improving TJ protein integrity, and reducing BBB permeability. Consequently, this treatment may promote neurological function recovery after IS.

Meta-analysis of trigger timing in normal responders undergoing GnRH antagonist ovarian hyperstimulation protocol.

IMPORTANCE: The first meta-analysis focused only on gonadotropin-releasing hormone (GnRH) antagonists, which helped determine the effect of delay trigger on pregnancy outcomes. OBJECTIVE: To evaluate the impact of delay trigger compared with standard trigger in normal responders undergoing GnRH antagonist protocol in improving pregnancy outcomes. METHODS: Studies published before April 2023 in PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, VIP and CBM databases were searched. Randomized controlled trials (RCTs) and cohort studies conducted in normal responders reporting the efficacy of delay trigger using GnRH antagonist protocol were included. Data were combined to calculate mean differences (MD) for continuous variables and odd ratios (OR) for categorical variables with their corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran's Q test. RESULTS: Endpoints, including clinical pregnancy rate (CPR), live birth rate (LBR), the number of oocyte retrievals and embryos, and fertilization rate, were analyzed. Six (6) clinical studies (4 RCTs and 2 cohort studies) with 1,360 subjects were included. The pooled results showed that the number of oocyte retrievals (MD: 1.20, 95% CI: 1.10, 1.30, p < 0.01), fertilization rate (MD: 0.64, 95% CI: 0.29, 0.99, p < 0.01) and days of stimulation (MD: 0.95; 95% CI: 0.54, 1.37; p < 0.01) in the delay trigger group was significantly higher than that in the standard trigger group. However, there was no significant difference in the number of embryos (MD: 0.19, 95% CI: -0.29, 0.67, p = 0.44), CPR (OR: 1.12; 95% CI: 0.72, 1.75; p = 0.062), and LBR (OR: 1.23; 95% CI: 0.90, 1.66; p = 0.19) between the two trigger groups. CONCLUSION: Delaying trigger time in GnRH antagonist protocol increased the number of oocytes retrieved but not the number of embryos. Furthermore, delay trigger shot was not associated with a clinical benefit towards CPR and LBR in women who underwent fresh embryo transfer cycles. TRIAL REGISTRATION: The International Prospective Register of Systematic Reviews (PROSPERO), registration number: CRD42023413217.

The transcriptional landscape of Populus pattern/effector-triggered immunity and how PagWRKY18 involved in it.

Plants trigger a robust immune response by activating massive transcriptome reprogramming through crosstalk between PTI and ETI. However, how PTI and ETI contribute to the quantitative or/and qualitative output of immunity and how they work together when both are being activated were unclear. In this study, we performed a comprehensive overview of pathogen-triggered transcriptomic reprogramming by analyzing temporal changes in the transcriptome up to 144 h after Colletotrichum gloeosporioides inoculated in Populus. Moreover, we constructed a hierarchical gene regulatory network of PagWRKY18 and its potential target genes to explore the underlying regulatory mechanisms of PagWRKY18 that are not yet clear. Interestingly, we confirmed that PagWRKY18 protein can directly bind the W-box elements in the promoter of a transmembrane leucine-rich repeat receptor-like kinase, PagSOBIR1 gene, to trigger PTI. At the same time, PagWRKY18 functions in disease tolerance by modulation of ROS homeostasis and induction of cell death via directly targeting PagGSTU7 and PagPR4 respectively. Furthermore, PagPR4 can interact with PagWRKY18 to inhibit the expression of PagPR4 genes, forming a negative feedback loop. Taken together, these results suggest that PagWRKY18 may be involved in regulating crosstalk between PTI and ETI to activate a robust immune response and maintain intracellular homeostasis.

Coinoculation of arbuscular mycorrhizal fungi and rhizobia stimulates atrazine dissipation by changing the atrazine-degrading bacterial community at the soil aggregate scale.

As a potential low-cost and environmentally friendly strategy, bioremediation of herbicide polluted soil has attracted increasing attention. However, there is a lack of knowledge regarding the response of the atrazine-degrading bacterial community to coinoculation of arbuscular mycorrhizal (AM) fungi and rhizobia for atrazine dissipation. In this study, a pot experiment was conducted with AM fungi Glomus mosseae (AM), rhizobia Rhizobium trifolii TA-1 (R) and their coinoculation (AMR) with atrazine. In each treatment, the atrazine-degrading bacterial community of four soil size aggregates, namely large macroaggregates (LMa), small macroaggregates (SMa), microaggregates (Mia) and primary particles (P) were investigated. The results showed that the atrazine residue concentration was lowest in AMR, and that in LMa was also significantly lower than that in the other smaller aggregate sizes. Overall, inoculation, the aggregate fraction and their interaction had significant effects on soil TN, SOC, AP and pH. For the atrazine-degrading bacterial community, the Chao1 index increased with decreasing particle size, but the Shannon index decreased. Moreover, the abundances of the dominant atrazine-degrading bacterial genera Arthrobacter, Bacillus, Marmoricola and Nocardioides in the Mia and P particle size groups were greater than those in the LMa and SMa groups in each treatment. The bacterial communities in the Mia and P particle sizes in each treatment group were more complex. Therefore, coinoculation of AM fungi and rhizobia stimulated atrazine dissipation by changing the atrazine-degrading bacterial community, and the response of the atrazine-degrading bacterial community to each aggregate size varied depending on its distinct soil physicochemical properties.

Self-reduced MXene-Metal interaction electrochemiluminescence support with synergistic electrocatalytic and photothermal effects for the bimodal detection of ovarian cancer biomarkers.

Novel two-dimensional MXene with unique optical and electrical properties has become a new focus in the field of sensing. In particular, their metallic conductivity, good biocompatibility and high anchoring ability to biomaterials make them attractive candidates. Despite such remarkable properties, there are certain limitations, such as low oxidative stability. MXene-Metal interactions are an effective strategy to maintain the long-term stability of MXene, while also improving the electrochemical activity and optical properties. Herein, a series of MXene/Ag nanocomposites including Ti3C2/Ag, Nb2C/Ag and V2C/Ag were designed based on the surface chemistry characteristics of MXene, where MXene served as the substrate for in-situ growth of silver nanoparticles via self-reduction of Ag(NH3)2+. The results showed that V2C MXene has the strongest self-reducing ability due to its multiple variable valence states, larger interlayer space and more reactive groups. Moreover, V2C/Ag exhibited unexpected oxygen reduction reaction catalytic activity and photothermal performance. In view of which, an electrochemiluminescence-photothermal (ECL-photothermal) immunosensor was developed using V2C/Ag as ECL anchor and photothermal reagent for ultrasensitive detection of Lipolysis stimulated lipoprotein receptor. This work not only provides a simple and effective synthesis method of MXene supported metal nanocomposites, but also provides more inspirations for exploring the efficient biosensing strategies.

Identification of the Near Full-Length Genome of a Novel HIV-1 CRF01_AE/CRF07_BC Recombinant in Hebei Province, China.

To analyze the genetic structure and recombination characteristics of a newly discovered HIV-1 unique recombinant form (URF) isolated in Hebei Province, China, viral RNA was extracted from the plasma sample of the infected individual and reverse transcribed to cDNA. Two overlapping segments of the HIV-1 genome were amplified using a near-endpoint dilution method. Recombinant breakpoints were determined using RIP, jpHMM, and SimPlot 3.5.1 software. MEGA 6.0 software was used to construct a neighbor-joining phylogenetic tree. The near full-length genome sequence (8,862 bp) of a recombinant of CRF01_AE/CRF07_BC was obtained. The genome comprised at least seven overlapping segments, including four CRF01_AE and three CRF07_BC segments, with CRF01_AE as the backbone. A URF virus between CRF01_AE and CRF07_BC was amplified and characterized in this study. Parental viruses were homologous with HIV-1 strains prevalent among men who have sex with men in northern China and may originate from sexual transmission of local HIV-1 strains in Hebei Province.

Risk factors for postoperative delirium in elderly patients undergoing heart valve surgery with cardiopulmonary bypass.

BACKGROUND: The aim of this study was to identify the risk factors for postoperative delirium (POD) in elderly patients undergoing heart valve surgery with cardiopulmonary bypass (CPB). METHODS: Elderly patients undergoing elective heart valve surgery with CPB in The First Affiliated Hospital of Wenzhou Medical University between March 2022 and March 2023 were selected for this investigation. They were divided into a POD group and a non-POD group. Their baseline information was collected and recorded, and the patients were subjected to neurocognitive function assessment using the Mini-Mental State Examination and the Montreal Cognitive Assessment scales before surgery. We also recorded their intraoperative indicators such as duration of surgery, duration of CPB, duration of aortic cross-clamp, blood transfusion, and postoperative indicators such as duration of mechanical ventilation, postoperative 24-hour drainage volume, and pain score. Regional cerebral oxygen saturation was monitored intraoperatively by near-infrared spectroscopy based INVOS5100C Regional Oximeter. Patients were assessed for the occurrence of POD using Confusion Assessment Method for the Intensive Care Unit, and logistic regression analysis of risk factors for POD was performed. RESULTS: The study finally included 132 patients, with 47 patients in the POD group and 85 ones in the non-POD group. There were no significant differences in baseline information and preoperative indicators between the two groups. However, marked differences were identified in duration of surgery, duration of CPB, duration of aortic cross-clamp, duration of postoperative mechanical ventilation, postoperative length of stay in cardiac intensive care unit, postoperative length of hospital stay, intraoperative blood transfusion, postoperative pain score, and postoperative 24-hour drainage volume between the two groups (p < 0.05). Additionally, the two groups had significant differences in rScO2 at each intraoperative time point and in the difference of rScO2 from baseline at each intraoperative time point (p < 0.05). Multivariate logistic regression analysis showed that duration of surgery > 285 min (OR, 1.021 [95% CI, 1.008-1.035]; p = 0.002), duration of postoperative mechanical ventilation > 23.5 h (OR, 6.210 [95% CI, 1.619-23.815]; p = 0.008), and postoperative CCU stay > 3.5 d (OR, 3.927 [95% CI, 1.046-14.735]; p = 0.043) were independent risk factors of the occurrence of POD while change of rScO2 at T1>50.5 (OR, 0.832 [95% CI 0.736-0.941]; p = 0.003) was a protective factor for POD. CONCLUSION: Duration of surgery duration of postoperative mechanical ventilation and postoperative CCU stay are risk factors for POD while change of rScO2 at T1 is a protective factor for POD in elderly patients undergoing heart valve surgery with CPB.

Moderate grazing increased carbon, nitrogen and phosphorus storage in plants and soil in the Eurasian meadow steppe ecosystem.

The effects of grazing on the cycling of carbon (C), nitrogen (N) and phosphorus (P) in grassland ecosystems are complex. Uncertainty still exists as regards the allocation of C, N and P storage amounts in grazed ecosystems in Inner Mongolia, situated at the eastern end of the Eurasian dryland. Based on the long-term cattle grazing experimental platform in the Hulun Buir meadow steppe of Inner Mongolia, a 3-year (2019-2021) field control experiment was conducted to assess how the grazing intensity influenced the quantities of C, N and P stored in canopy biomass, root, litter and soil compartments. We examined the relationships between the different pools and their regulatory pathways at the ecosystem level across six grazing intensities. In general, grazing increased the aboveground N and P contents but decreased the aboveground biomass C content and nutrient storage amounts in aboveground biomass, roots and litter. The grazing intensity of 0.34 AU ha-1 increased soil organic carbon, total nitrogen and total phosphorus storage amounts, with the soil accounting for 98 % of total reserves on average. Grazing affected soil pH， nutrient contents, above- and belowground biomass and soil environmental factors such as soil bulk density, which in turn affected C, N and P storage in the ecosystem according to the results of the structural equation model; therefore, grazing intensity can be an important factor regulating the input and output of nutrients in the ecosystem. In the future, for adaptive management of grasslands, moderate grazing could effectively increase C, N and P storage in meadow steppe ecosystems and ensure the nutrient balance and long-term sustainable development.

Is radiotherapy necessary for upper rectal cancer underwent curative resection? A retrospective study of 363 patients.

BACKGROUND: To investigate the impact of radiotherapy (RT) on recurrence and survival in patients with locally advanced upper rectal cancer underwent curative resection. METHODS: 363 locally advanced upper rectal cancer cases were identified from the database of our hospital from 2010 to 2018. All patients underwent curative resection and had the lower margin of the tumor located 10-15 cm from the anal verge, among them, 69 patients received pre- or post-operative radiotherapy and 294 patients without. Local control and survivals were compared, and stratification grouping based on European Society for Medical Oncology risk factors were further compared. 1:2 propensity score matching analysis was used to reduce the impact of confounding factors. RESULTS: There were 207 patients after 1:2 matching (RT group:non-RT group = 69:138). The 5-year overall survival (OS) of the RT group and non-RT group after matching was 84.1% and 80.9%, respectively(P = 0.440); the 5-year local recurrence-free survival (LRFS) was 96.5% and 94.7%, respectively(P = 0.364); the 5-year distant metastasis-free survival (DMFS) was 76.8% and 76.9%, respectively(P = 0.531). Subgroup analysis showed that radiotherapy could not significantly improve the overall survival, local recurrence, and distant metastasis with or without poor prognostic features. In the high-risk subgroup, the 5-year OS was 76.9% and 79.6% for patients treated with radiotherapy and without (P = 0.798), LRFS was 94.8% and 94.2%, respectively (P = 0.605), DMFS 68.7% and 74.7%, respectively (P = 0.233). CONCLUSIONS: Our results suggest that radiotherapy could not improve local control and survival for locally advanced upper rectal cancer patients underwent curative resection, even in the cases with poor prognostic features.