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Abstract The mid-Piacenzian warm period (MPWP, ~3.264–3.025 Ma) has gained widespread interest due to its partial analogy with future climate. However, quantitative data–model comparison of East Asian Summer Monsoon (EASM) precipitation during the MPWP is relatively rare, especially due to problems in decoding the imprint of physical processes to climate signals in the records. In this study, pollen-based precipitation records are reconstructed and compared to the multi-model ensemble mean of the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2). We find spatially consistent precipitation increase in most simulations but a spatially divergent change in MPWP records. We reconcile proxy data and simulation by decomposing physical processes that control precipitation. Our results 1) reveal thermodynamic control of an overall enhancement of EASM precipitation and 2) highlight a distinct control of thermodynamic and dynamical processes on increases of tropical and subtropical EASM precipitation, reflecting the two pathways of water vapor supply that enhance EASM precipitation, respectively.

Abstract Background There is a correlation between nutritional status and treatment outcomes and long-term survival in MHD patients but there is limited research on the relationship between GNRI and IDH. This case-control study aimed to investigate the correlation between Geriatric Nutritional Risk Index (GNRI) and intradialytic hypotension (IDH) in elderly patients undergoing maintenance hemodialysis (MHD). Methods This study was carried out on 129 cases of MHD patients with IDH and 258 non-IDH-controls in Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China, between June 2020 and May 2022. Professional researchers collected patients’ general information on gender, primary disease, dialysis-related indicators, anthropometric measures, laboratory biochemicals, and GNRI. Logistic regression analysis was used to evaluate the correlation between GNRI and IDH. Results A total of 385 elderly MHD patients were included. Compared with GNRI Q4 group, the odds ratios for the risk of IDH in GNRI Q3 group, GNRI Q2 group, and GNRI Q1 group of elderly MHD patients were 1.227, 2.196, and 8.350, respectively, showing a significant downward trend (P-trend

A proper dietary electrolyte balance (dEB) is essential to ensure optimal growth performance of piglets. In the low-protein diet, this balance may be affected by the reduction of soybean meal and the inclusion of high levels of synthetic amino acids. The objective of this experiment was to evaluate the optimal dEB of low-protein diets and its impact on the growth performance of piglets. A total of 108 piglets (initial age of 35 d) were randomly divided into 3 groups with 6 replicates of 6 pigs each as follows: low electrolyte diet (LE group; dEB = 150 milliequivalents [mEq]/kg); medium electrolyte diet (ME group; dEB = 250 mEq/kg); high electrolyte diet (HE group; dEB = 350 mEq/kg). Results indicated that the LE and HE diet significantly decreased the average daily gain, average daily feed intake, and crude protein digestibility (P

Abstract Background One of the most prevalent illnesses of the shoulder is rotator cuff tendinosis, which is also a major contributor to shoulder discomfort and shoulder joint dysfunction. According to statistics, rotator cuff tendinosis occurs in 0.3–5.5% of cases and affects 0.5–7.4% of people annually. It will be necessary to conduct a meta-analysis to evaluate the efficacy of hypertonic glucose proliferation therapy in the treatment of rotator cuff problems. Methods The databases Cochrane PubMed, Library, Web of Science and EMbase, are retrieved by the computer. Individuals with rotator cuff lesions in the intervention group were treated with hypertonic dextrose proliferation therapy, whereas individuals in the control condition were treated with a placebo. Outcome markers for rotator cuff lesions patients; Pursuant to studies, the visual analogue scale (VAS) score, the shoulder pain & disability index (SPADI), & other metrics are used to evaluate the effects of hypertonic dextrose proliferation treatment on individuals with rotator cuff diseases. After carefully evaluating the calibre of the literature, data analysis was performed utilising the RevMan 5.3 programme. Results Meta-analysis finally contained 6 papers. In six investigations, the test & control group’s VAS scores improved, with the test team’s score considerably outperforming the control team [standardized mean difference (SMD): 1.10; 95% Cl: 0.37,1.83; P

BackgroundGlaucoma (GLAU), Age-related Macular Degeneration (AMD), Retinal Vein Occlusion (RVO), and Diabetic Retinopathy (DR) are common blinding ophthalmic diseases worldwide.PurposeThis approach is expected to enhance the early detection and treatment of common blinding ophthalmic diseases, contributing to the reduction of individual and economic burdens associated with these conditions.MethodsWe propose an effective deep-learning pipeline that combine both segmentation model and classification model for diagnosis and grading of four common blinding ophthalmic diseases and normal retinal fundus.ResultsIn total, 102,786 fundus images of 75,682 individuals were used for training validation and external validation purposes. We test our model on internal validation data set, the micro Area Under the Receiver Operating Characteristic curve (AUROC) of which reached 0.995. Then, we fine-tuned the diagnosis model to classify each of the four disease into early and late stage, respectively, which achieved AUROCs of 0.597 (GL), 0.877 (AMD), 0.972 (RVO), and 0.961 (DR) respectively. To test the generalization of our model, we conducted two external validation experiments on Neimeng and Guangxi cohort, all of which maintained high accuracy.ConclusionOur algorithm demonstrates accurate artificial intelligence diagnosis pipeline for common blinding ophthalmic diseases based on Lesion-Focused fundus that overcomes the low-accuracy of the traditional classification method that based on raw retinal images, which has good generalization ability on diverse cases in different regions.

Abstract Ultralong room‐temperature phosphorescent (URTP) materials have attracted wide attention in anti‐counterfeiting, optoelectronic display, and bio‐imaging due to their special optical properties. However, room‐temperature blue phosphorescent materials are very scarce during applications because of the need to simultaneously populate and stabilize high‐energy excited states. In this work, a stepwise stiffening chromophore strategy is proposed to suppress non‐radiative jump by continuously reducing the internal spin of the chromophore, and successfully developing a series of blue phosphorescent materials. Phosphorescence lifetimes of more than 3 s are achieved, with the longest lifetime reaching 5.44 s and lasting more than 70 s in the naked eye. As far as is know, this is the best result that has been reported. By adjusting the chromophore conjugation, multicolor phosphorescences from cyan to green have been realized. In addition, these chromophores exhibit the same excellent optical properties in urea and polyvinyl alcohmance (PVA). Finally, these materials are successfully applied to luminescent displays.

IntroductionClubroot disease is a devastating soil borne disease caused by infection with Plasmodiophora brassicae, which primarily affects cruciferous plants. The microbial diversity of the soil is an essential indicator of its quality.MethodsThis study measured the physicochemical properties of the soil to study the effect of its microbial diversity on the infection of oilseed rape with P. brassicae. High-throughput sequences of the soil bacteria and fungi in the inter-root soils of P. brassicae were analyzed under different treatment conditions.ResultsIn the study, it was found that the efficiency of strain X216 in preventing and controlling the root disease of rapeseed was positively correlated with the amount of solution used to irrigate the root system. The results of the greenhouse and field trials showed that the efficiency of strain X216 against the root disease of rapeseed was 43.16% in the field and 62.14% in the greenhouse. Proteobacteria, Chloroflexi, Rozellomycota, and Basidiomycota are critical phylum in the development of clubroot disease. The application of biocontrol increased the relative abundance of Actinobacteria, Bacillus, Mesorhizobium, Mycobacterium, Streptomyces and Filobasidium, which affected the structure and abundance of microbial communities. A principal coordinate analysis showed that the microbial structure in the soil varied substantially in the bacterial community, and there was no significant difference in soil structure in the fungal community.DiscussionThe occurrence of clubroot disease affected the structure of inter-root microbial community composition in the soil, which resulted in a decrease in its community diversity. The application of the biocontrol bacterium X216 increased the soil microbial diversity. It effectively reduced the occurrence of P. brassicae, and this study provides a basis to study the microbial diversity in cruciferous crops.

Abstract The Lhasa‐Qiangtang collision closed the Meso‐Tethys Ocean, but the exact timing of this event remains hotly debated. Here, we present geochronological and paleomagnetic analyses conducted on Cretaceous volcanics from western Qiangtang to constrain the Lhasa‐Qiangtang collision in western Tibet. Our investigations yield a paleolatitude of ∼30.5 ± 5.0°N for western Qiangtang during ca. 110–100 Ma. A reanalysis of previously acquired Mesozoic‐Cenozoic paleomagnetic data from western Qiangtang suggests a stationary position during ca. 136–34 Ma. Examination of paleomagnetic data from western Lhasa reveals a significant reduction in northward paleolatitudinal motion during the Early Cretaceous, dropping from ∼12.3 cm/yr to nearly zero. Integration of our paleomagnetic findings with available geological records has led to conclude that the Lhasa‐Qiangtang collision in western Tibet occurred at ca. 132 Ma. Additionally, we infer that crustal shortening on the order of ∼1,000 km happened between Lhasa and Qiangtang during the Early Cenozoic.

Colon cancer, thyroid cancer, and melanoma are common malignant tumors that seriously threaten human health globally. The B-Raf proto-oncogene, serine/threonine kinase (BRAF)(V600E) mutation is an important driver gene mutation in these cancer types. In this study, we identified that collagen triple helix repeat containing 1 (CTHRC1) expression was associated with the BRAF(V600E) mutation in colon cancer, thyroid cancer, and melanoma. Based on database analysis and clinical tissue studies, CTHRC1 was verified to correlate with poor prognosis and worse clinicopathological features in colon cancer and thyroid cancer patients, but not in patients with melanoma. Several signaling pathways, immune cell infiltration, and immunotherapy markers were associated with CTHRC1 expression. Additionally, a high level of CTHRC1 was correlated with decreased sensitivity to antitumor drugs (vemurafenib, PLX-4720, dabrafenib, and SB-590885) targeting the BRAF(V600E) mutation. This study provides evidence of a significant correlation between CTHRC1 and the BRAF(V600E) mutation, suggesting its potential utility as a diagnostic and prognostic biomarker in human colon cancer, thyroid cancer, and melanoma.

This study uses the network flow theory to optimize regional water resource allocation. In order to solve the problem of inefficient utilization of water resources with decentralized decision-making by different administrative units, a regional water resource networking and joint dispatching model with multi-objective nonlinear characteristics based on the network flow theory (hereinafter referred to as the network flow model) is constructed in the study. The network flow model was simulated and applied in the Xin-Sheng area of the Cao'e River, a tributary of the Qiantang River, and the results of the study showed that the network flow model scheduling increased significantly in efficiency compared with the current conventional scheduling, with an increase of 35.24 and 9.91% in the water resource utilization rate in the two typical years of 2019 and 2022, respectively, and showed that 2022, which has less rainfall, has a better effect than 2019. The study concludes that the network flow model can effectively improve the efficiency of water resource utilization, solve the problem of water resource imbalance between cities in the region, and play a positive role in the construction of the national water network. HIGHLIGHTS The aim of this study is to construct a network flow model based on nonlinear multi-objective optimization.; Scheduling objective is to maximize water use under industry-dominated economic conditions.; The network flow model couples incentive compatibility mechanisms between different administrative agents.; Network flow modeling can test whether certain administrative units have over-exploited resources.;

Abstract Background Ropivacaine, a local anesthetic, exhibits anti-tumor effects in various cancer types. However, its specific functions and the molecular mechanisms involved in breast cancer cell stemness remain elusive. Methods The effects of ropivacaine on breast cancer stemness were investigated by in vitro and in vivo assays (i.e., FACs, MTT assay, mammosphere formation assay, transwell assays, western blot, and xenograft model). RNA-seq, bioinformatics analysis, Western blot, Luciferase reporter assay, and CHIP assay were used to explore the mechanistic roles of ropivacaine subsequently. Results Our study showed that ropivacaine remarkably suppressed stem cells-like properties of breast cancer cells both in vitro and in vivo. RNA-seq analysis identified GGT1 as the downstream target gene responding to ropivacaine. High GGT1 levels are positively associated with a poor prognosis in breast cancer. Ropivacaine inhibited GGT1 expression by interacting with the catalytic domain of AKT1 directly to impair its kinase activity with resultant inactivation of NF-κB. Interestingly, NF-κB can bind to the promoter region of GGT1. KEGG and GSEA analysis indicated silence of GGT1 inhibited activation of NF-κB signaling pathway. Depletion of GGT1 diminished stem phenotypes of breast cancer cells, indicating the formation of NF-κB /AKT1/GGT1/NF-κB positive feedback loop in the regulation of ropivacaine-repressed stemness in breast cancer cells. Conclusion Our finding revealed that local anesthetic ropivacaine attenuated breast cancer stemness through AKT1/GGT1/NF-κB signaling pathway, suggesting the potential clinical value of ropivacaine in breast cancer treatment.

Abstract Background Tubulointerstitial fibrosis plays an important role in the progression of diabetic kidney disease (DKD). Sacubitril/valsartan (Sac/Val) exerts a robust beneficial effect in DKD. However, the potential functional effect of Sac/Val on tubulointerstitial fibrosis in DKD is still largely unclear. Methods Streptozotocin-induced diabetic mice were given Sac/Val or Val by intragastric administration once a day for 12 weeks. The renal function, the pathological changes of tubule injury and tubulointerstitial fibrosis, as well as mitochondrial morphology of renal tubules in mice, were evaluated. Genome-wide gene expression analysis was performed to identify the potential mechanisms. Meanwhile, human tubular epithelial cells (HK-2) were cultured in high glucose condition containing LBQ657/valsartan (LBQ/Val). Further, mitochondrial functions and Sirt1/PGC1α pathway of tubular epithelial cells were assessed by Western blot, Real-time-PCR, JC-1, MitoSOX or MitoTracker. Finally, the Sirt1 specific inhibitor, EX527, was used to explore the potential effects of Sirt1 signaling in vivo and in vitro. Results We found that Sac/Val significantly ameliorated the decline of renal function and tubulointerstitial fibrosis in DKD mice. The enrichment analysis of gene expression indicated metabolism as an important modulator in DKD mice with Sac/Val administration, in which mitochondrial homeostasis plays a pivotal role. Then, the decreased expression of Tfam and Cox IV;, as well as changes of mitochondrial function and morphology, demonstrated the disruption of mitochondrial homeostasis under DKD conditions. Interestingly, Sac/Val administration was found to restore mitochondrial homeostasis in DKD mice and in vitro model of HK-2 cells. Further, we demonstrated that Sirt1/PGC1α, a crucial pathway in mitochondrial homeostasis, was activated by Sac/Val both in vivo and in vitro. Finally, the beneficial effects of Sac/Val on mitochondrial homeostasis and tubulointerstitial fibrosis was partially abolished in the presence of Sirt1 specific inhibitor. Conclusions Taken together, we demonstrate that Sac/Val ameliorates tubulointerstitial fibrosis by restoring Sirt1/PGC1α pathway-mediated mitochondrial homeostasis in DKD, providing a theoretical basis for delaying the progression of DKD in clinical practice.

AimsPrimary pigmented nodular adrenocortical disease (PPNAD), as a rare kind of Cushing’s syndrome, is frequently misdiagnosed. To get a better understanding of the disease, we analyzed the clinical characteristics and pathogenic variants of PPNAD.MethodsDatabases were searched, and the pathogenic variants and clinical manifestations of patients were summarized from the relevant articles.ResultsA total of 210 patients in 86 articles were enrolled with a median age of 22 and a female-to-male ratio of 2:1. Sixty-six (31.43%) patients were combined with Carney complex (CNC) and 94.29% were combined with osteoporosis/osteopenia. Among 151 patients who underwent genetic testing, 87.42% (132/151) had pathogenic variants. Six gene mutations (PRKAR1A, PDE11A, PRKACA, CTNNB1, PDE8B, and ARMC5) were detected in the patients. The most common mutation was PKAR1A, accounting for 79.47% (120/151). There was a significant correlation between PRKAR1A pathogenic variant and spotty skin pigmentation in CNC concurrent with PPNAD (p < 0.05). Among pregnant patients with PPNAD, those without surgical treatment and with bilateral adrenalectomy suffered from a high-risk perinatal period. However, patients with unilateral adrenalectomy presented a safe perinatal period.ConclusionsFor young patients with Cushing’s syndrome, especially female patients with spotty skin pigmentation and osteoporosis/osteopenia, PPNAD should be considered. Unilateral adrenal resection may be considered as an option for women with fertility needs. In view of the difficulty of PPNAD diagnosis, genetic testing before surgery might be a reasonable option. Patients with PPNAD with spotty skin pigmentation should consider the PRKAR1A pathogenic variant and pay attention to CNC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42023416988.

Abstract Iron overload is common in cardiovascular disease, it is also the factor that drives ferroptosis. Noncoding RNAs play an important role in heart disease; however, their regulatory role in iron overload‐mediated ferroptosis remains much unknown. In our study, the iron overload model in mice was constructed through a high‐iron diet, and ammonium iron citrate treatment was used to mimic iron overload in vitro. We found iron overload induced ferroptosis in cardiomyocytes, which was dependent on the high expression of transferrin receptor (TFRC). MiR‐31‐5p was downregulated during iron overload; it inhibited cardiomyocyte ferroptosis by targeting TFRC. CircPIK3C2A, a highly expressed circRNA in the heart, was upregulated when iron was overloaded. CircPIK3C2A enhanced the expression of TFRC by sponging miR‐31‐5p and promoted ferroptosis during iron overload. Our results reveal a novel mechanistic insight into noncoding RNA‐based ferroptosis and identify the circPIK3C2A/miR‐31‐5p/TFRC axis as a promising therapeutic target for myocardial damage.

Abstract The incidence rate of cancer is increasing year by year due to the aging of the population, unhealthy living, and eating habits. At present, surgery and medication are still the main treatments for cancer, without paying attention to the impact of individual differences in health management on cancer. However, increasing evidence suggests that individual psychological status, dietary habits, and exercise frequency are closely related to the risk and prognosis of cancer. The reminder to humanity is that the medical concept of the unified treatment plan is insufficient in cancer treatment, and a personalized treatment plan may become a breakthrough point. On this basis, the concept of “Humanistic Health Management” (HHM) is proposed. This concept is a healthcare plan that focuses on self‐health management, providing an accurate and comprehensive evaluation of individual lifestyle habits, psychology, and health status, and developing personalized and targeted comprehensive cancer prevention and treatment plans. This review will provide a detailed explanation of the relationship between psychological status, dietary, and exercise habits, and the regulatory mechanisms of cancer. Intended to emphasize the importance of HHM concept in cancer prevention and better prognostic efficacy, providing new ideas for the new generation of cancer treatment.

Compared to conventional irrigation and fertilization, the Water-fertilizer coupling can significantly enhance the efficiency of water and fertilizer utilization, thereby promoting crop growth and increasing yield. Targeting the challenges of poor crop growth, low yield, and inefficient water and fertilizer utilization in the arid region of northwest China under conventional irrigation and fertilization practices. Therefore, a two-year on-farm experiment in 2022 and 2023 was conducted to study the effects of water-fertilizer coupling regulation on pumpkin growth, yield, water consumption (ET), and water and fertilizer use efficiency. Simultaneously the comprehensive evaluation of multiple objectives was carried out using principal component analysis (PCA) methods, so as to propose an suitable water-fertilizer coupling regulation scheme for the region. The experiment was set up as a two-factor trial using water-fertilizer integration technology under three irrigation volume (W1 = 37.5 mm, W2 = 45.5 mm, W3 = 52.5mm) and three organic fertilizer application amounts (F1 = 3900-300 kg ha-1, F2 = 4800-450 kg·ha-1, F3 = 5700-600 kg·ha-1), with the traditional irrigation and fertilization scheme from local farmers as control treatments (CK). The results indicated that irrigation volume and organic fertilizer application significantly affected pumpkin growth, yield, and water and fertilizer use efficiency (P

The recycling of industrial solid by-products such as red mud (RM) has become an urgent priority, due to their large quantities and lack of reutilization methods can lead to resource wastage. In this work, RM was employed to fabricate green hydrochar (HC) to prepare zero-valent iron (ZVI) modified carbonous materials, and conventional iron salts (IS, FeCl3) was applied as comparison, fabricated HC labeled as RM/HC and IS/HC, respectively. The physicochemical properties of these HC were comprehensively characterized. Further, hexavalent chromium (Cr(VI)) removal performance was assessed (375.66 and 337.19 mg/g for RM/HC and IS/HC, respectively). The influence of dosage and initial pH were evaluated, while isotherms, kinetics, and thermodynamics analysis were also conducted, to mimic the surface interactions. The stability and recyclability of adsorbents also verified, while the practical feasibility was assessed by bok choy-planting experiment. This work revealed that RM can be used as a high value and green fabricant for HC the effective removal of chromium contaminants from the wastewater.

Abstract The construction of polymer-based mimicry on cell surface to manipulate cell behaviors and functions offers promising prospects in the field of biotechnology and cell therapy. However, precise control of polymer grafting sites is essential to successful implementation of biomimicry and functional modulation, which has been overlooked by most current research. Herein, we report a biological site-selected, in situ controlled radical polymerization platform for living cell surface engineering. The method utilizes metabolic labeling techniques to confine the growth sites of polymers and designs a Fenton-RAFT polymerization technique with cytocompatibility. Polymers grown at different sites (glycans, proteins, lipids) have different membrane retention time and exhibit differential effects on the recognition behaviors of cellular glycans. Of particular importance is the achievement of in situ copolymerization of glycomonomers on the outermost natural glycan sites of cell membrane, building a biomimetic glycocalyx with distinct recognition properties.

Abstract Changing thermal regime is one of the key mechanisms driving seismogenic behaviors at cold megathrusts, but it is difficult to interpret warm subduction zones such as Vanuatu for the temperatures are higher than that accommodates shallow brittle failures. We construct a 3-D thermomechanical model to clarify the thermal structure that controls tectonic seismicity in Vanuatu and predict a warm circumstance associated with abundant seismicity. Results reveal a heterogeneous slab ranging from 300 °C to over 900 °C from the Moho to subvolcanic depth. The subduction seismicity corresponds well to the plate interface where dynamic thermal dehydration is focused. The transformation from hydrated basalts to eclogites along the slab facilitates the occurrence of intense earthquakes and slips. Multistage mineralogical metamorphism affects the dynamic stability of megathrusts and favors the generation of active interplate large events. Therefore, slab thermal dehydration plays a greater role than slab temperature condition in influencing the subduction earthquake distribution in warm subduction systems.

Abstract Background Previous studies have demonstrated that natural killer (NK) cells migrated into the liver from peripheral organs and exerted cytotoxic effects on hepatocytes in virus-induced liver failure. Aim This study aimed to investigate the potential therapeutic role of chemokine receptors in the migration of NK cells in a murine hepatitis virus strain 3 (MHV-3)-induced fulminant hepatic failure (MHV-3-FHF) model and its mechanism. Results By gene array analysis, chemokine (C–C motif) receptor 5 (CCR5) was found to have remarkably elevated expression levels in hepatic NK cells after MHV-3 infection. The number of hepatic CCR5+ conventional NK (cNK) cells increased and peaked at 48 h after MHV-3 infection, while the number of hepatic resident NK (rNK) cells steadily declined. Moreover, the expression of CCR5-related chemokines, including macrophage inflammatory protein (MIP)-1α, MIP-1β and regulated on activation, normal T-cell expressed and secreted (RANTES) was significantly upregulated in MHV-3-infected hepatocytes. In an in vitro Transwell migration assay, CCR5-blocked splenic cNK cells showed decreased migration towards MHV-3-infected hepatocytes, and inhibition of MIP-1β or RANTES but not MIP-1α decreased cNK cell migration. Moreover, CCR5 knockout (KO) mice displayed reduced infiltration of hepatic cNK cells after MHV-3 infection, accompanied by attenuated liver injury and improved mouse survival time. Adoptive transfer of cNK cells from wild-type mice into CCR5 KO mice resulted in the abundant accumulation of hepatic cNK cells and aggravated liver injury. Moreover, pharmacological inhibition of CCR5 by maraviroc reduced cNK cell infiltration in the liver and liver injury in the MHV-3-FHF model. Conclusion The CCR5-MIP-1β/RANTES axis played a critical role in the recruitment of cNK cells to the liver during MHV-3-induced liver injury. Targeted inhibition of CCR5 provides a therapeutic approach to ameliorate liver damage during virus-induced acute liver injury.

AbstractThe complete mitochondrial genome sequence of Goniurosaurus varius is 17778 bp in length (GenBank accession number OQ992199), containing 13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes. The gene order and orientation are identical to those of other Eublepharidae species in the GenBank database. Seven protein-coding genes (COX2, COX3, ND1, ND2, ND3, ND4 and CYTB) exhibit incomplete stop codon ‘T.’ Phylogenetic analysis revealed the monophyly of Goniurosaurus and Eublepharidae and suggested that G. varius is closely related to the lineage composed of G. luii and G. liboensis. Distinct from other published Eublepharidae species, G. varius contains an extra non-coding region between tRNA-Thr and tRNA-Pro, which may be formed by gene rearrangements. The complete mitochondrial genome will be helpful for further studies on the population genetics of this species and phylogenetic analyses of Eublepharidae.

Abstract Background Aedes albopictus is an invasive vector of serious Aedes-borne diseases of global concern. Habitat management remains a critical factor for establishing a cost-effective systematic strategy for sustainable vector control. However, the community-based characteristics of Ae. albopictus habitats in complex urbanization ecosystems are still not well understood. Methods A large-scale investigation of aquatic habitats, involving 12 sites selected as representative of four land use categories at three urbanization levels, was performed in Guangzhou, China during 2015–2017. The characteristics and dynamics of these Ae. albopictus habitats were assessed using habitat-type composition, habitat preference, diversity indexes and the Route index (RI), and the temporal patterns of these indexes were evaluated by locally weighted scatterplot smoothing models. The associations of RI with urbanization levels, land use categories and climatic variables were inferred using generalized additive mixed models. Results A total of 1994 potential habitats and 474 Ae. albopictus-positive habitats were inspected. The majority of these habitats were container-type habitats, with Ae. albopictus showing a particularly higher habitat preference for plastic containers, metal containers and ceramic vessels. Unexpectedly, some non-container-type habitats, especially ornamental ponds and surface water, were found to have fairly high Ae. albopictus positivity rates. Regarding habitats, the land use category residential and rural in Jiangpu (Conghua District, Guangzhou) had the highest number of Ae. albopictus habitats with the highest positive rates. The type diversity of total habitats (H-total) showed a quick increase from February to April and peaked in April, while the H-total of positive habitats (H-positive) and RIs peaked in May. RIs mainly increased with the monthly average daily mean temperature and monthly cumulative rainfall. We also observed the accumulation of diapause eggs in the winter and diapause termination in the following March. Conclusions Ecological heterogeneity of habitat preferences of Ae. albopictus was demonstrated in four land use categories at three urbanization levels. The results reveal diversified habitat-type compositions and significant seasonal variations, indicating an ongoing adaptation of Ae. albopictus to the urbanization ecosystem. H-positivity and RIs were inferred as affected by climatic variables and diapause behavior of Ae. albopictus, suggesting that an effective control of overwintering diapause eggs is crucial. Our findings lay a foundation for establishing a stratified systematic management strategy of Ae. albopictus habitats in cities that is expected to complement and improve community-based interventions and sustainable vector management. Graphical Abstract

The Paleogene sandstone reservoir of Huizhou Sag is an important target for deep exploration in the Pearl River Mouth Basin, South China Sea. Because of the intense volcanic activity, it had a significant impact on the development of reservoirs, making it hard to predict. The diagenetic process of volcanogenic sediment and their influence of the reservoir have been studied by petrographic analysis, X-ray diffraction and scanning electron microscopy (SEM). Four types of volcanogenic sediment were identified: volcanic dust (

Introduction Liver disease causes 2 million deaths annually, accounting for 4% of all deaths worldwide. Liver surgery is one of the effective therapeutic options. Bleeding is a major complication during liver surgery. Perioperative bleeding and allogeneic blood transfusion may deteriorate the prognosis. Terlipressin (TP), a synthetic analogue of the antidiuretic hormone, may reduceblood loss during abdominal surgery. Several clinical centres have attempted to use TP during liver surgery, but the evidence for its effectiveness in reducing blood loss and the need for allogeneic blood transfusion, as well as its safety during the perioperative period, remains unclear. The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of TP in reducing blood loss and allogeneic blood transfusion needs during liver surgery.Methods and analysis We will search PubMed, EMBASE, the Cochrane Library and Web of Science for studies on perioperative use of TP during liver surgery from inception to July 2023. We will limit the language to English, and two reviewers will independently screen and select articles. The primary study outcomes are estimated blood loss and the need for allogeneic blood transfusion. Secondary outcomes include operating time, intensive care unit stay, length of stay, intraoperative urine output, acute kidney injury rate, postoperative complications, hepatic and renal function during follow-up, and TP-related adverse effects. We will include studies that met the following criteria: (1) randomised controlled trials (RCTs), cohort studies or case-control studies; (2) the publication time was till July 2023; (3) adult patients (≥18 years old) undergoing elective liver surgery; (4) comparison of TP with other treatments and (5) the study includes at least one outcome. We will exclude animal studies, case reports, case series, non-original articles, reviews, paediatric articles, non-controlled trials, unpublished articles, non-English articles and other studies that are duplicates. We will use Review Manager V.5.3 software for meta-analysis and perform stratification analysis for the study quality of RCTs based on the Jadad score. For cohort or case-control studies, the study quality will be analysed based on Newcastle-Ottawa Scale scores. Grading of Recommendations, Assessment, Development and Evaluation will be used to assess confidence in the cumulative evidence. For primary outcomes, we will conduct subgroup analyses based on meta-regression. We will also perform leave-one-out sensitivity analyses to evaluate the effect of each individual study on the combined results by removing the individual studies one by one for outcomes with significant heterogeneity. The protocol follows the Cochrane Handbook for Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines.Ethics and dissemination This study is a secondary analysis of existing data; therefore, it does not require ethical approval. We will disseminate the results through peer-reviewed publications.PROSPERO registration number CRD42023450333.

ObjectiveTo investigate the effects of β-cell dysfunction on IVF outcomes in women with PCOS.MethodsThis retrospective cohort study includes 1,212 women with PCOS undergoing their first IVF cycle between September 2010 and December 2019. Beta-cell dysfunction was measured by homeostasis model assessment of β-cell function (HOMA-β) index.ResultsIn quartiles of HOMA-β, the incidence of miscarriage dramatically increased from 10.2% (Q1) to 31.1% (Q4) (Pfor trend

GEA-1, a proprietary stream cipher, was initially designed and used to protect against eavesdropping general packet radio service (GPRS) between the phone and the base station. Now, a variety of current mobile phones still support this standard cipher. In this paper, a structural weakness of the GEA-1 stream cipher that has not been found in previous works is discovered and analyzed. That is the probability that two different inputs of GEA-1 generate the identical keystream can be up to 2−7.30, which is quite high compared with an ideal stream cipher that generates random sequences. Based on this newfound weakness, a new practical distinguishing attack on GEA-1 is proposed, which shows that the keystreams generated by GEA-1 are far from random and can be easily distinguished with a practical time cost. After then, a new practical key recovery attack on GEA-1 is presented. It has a time complexity of 221.02 GEA-1 encryptions and requires only seven related keys, which is much less than the existing related key attack on GEA-1. The experimental results show that GEA-1 can be broken within about 41.75 s on a common PC in the related key setting. These cryptanalytic results show that GEA-1 cannot provide enough security and should be immediately prohibited to be supported in the massive GPRS devices.

IntroductionThe COVID-19 pandemic has caused untold damage to the socio-economic lives of people all over the world. Research has also demonstrated great inequality in the pandemic experience. In the UK as in many other countries, people from ethnic minority backgrounds and in working-class positions have suffered disproportionately more than the majority group and those in salariat positions in terms of income loss, financial difficulty, and vulnerability to infection. Yet little is known about how people coped in the daily lives and tried to maintain their well-being during the most difficult days of the pandemic through social capital.MethodsIn this paper, we draw data from the COVID-19 Survey in Five National Longitudinal Studies to address these questions. The survey covered the period from May 2020 to February 2021, the height of the pandemic in the UK. It contains numerous questions on contact, help and support among family, friends, community members, socio-political trust, and physical and mental health. We conceptualise three types of social capital and one type of overall well-being and we construct latent variables from categorical indicator variables. We analyse the ethnic and socio-economic determinants of the three types of social capital and their impacts on well-being.ResultsOur analysis shows that social capital plays very important roles on well-being, and that ethnic minority groups, particularly those of Pakistani/Bangladeshi and Black heritages, faced multiple disadvantages: their poorer socio-economic positions prevented them from gaining similar levels of social capital to those of the white group. However, for people with the same levels of social capital, the effects on well-being are generally similar.DiscussionSocio-economic (class) inequality is the root cause for ethnic differences in social capital which in turn affects people’s well-being.

WG-5 is a lightweight stream cipher proposed for usage in the resource-constrained devices, e.g., passive RFID tags, industrial controllers, contactless smart cards and sensors. In this paper, a weakness called slide property of WG-5 which has not been discovered in previous works is for the first time explored and analyzed. The result shows that the probability that two related key-IV pairs of WG-5 generate the shifted keystreams can be up to 2−20, which is significantly high compared with an ideal stream cipher that generates the random keystreams. The correctness and accuracy of this theoretical probability is confirmed experimentally. Based on the slide property of WG-5, some key recovery attacks on WG-5 in the related key setting are proposed. The cryptanalytic result shows that the 80-bit secret key of WG-5 can be recovered with a time complexity of 225.615, requiring 6 related keys and 80 keystream bits for each of 224.585 chosen IVs. The experimental result validates our attack and shows that WG-5 can be broken within about 92.054 seconds on a common PC in the related key setting. These results imply that the design of WG-5 is far from optimal and needs to be strengthened to provide enough security for the lightweight constrained applications.

Abstract The enhancement of immunotherapy is an emerging direction to develop highly effective and practical cancer therapeutic methods. Here a triply enhanced immunotherapy drug (TEID) is designed for ingeniously integrating in situ dual glycan reforming with perforation on cell membrane. The TEID is composed of galactose and neuraminidase conjugated streptolysin O (SLO‐Gal and SLO‐NEU), which are encapsulated in a hyaluronic acid (HA) shell for targeted recognition to tumor tissue via cell surface CD44. After targeted delivery and HAase‐mediated degradation in the tumor region, the TEID releases SLO‐Gal and SLO‐NEU, which can easily anchor Gal and NEU on the tumor cell membrane via the perforation of SLO to perform dual glycan reforming for the introduction of Gal and the cleavage of sialic acid. The former can activate immune cells to secret cytokines for immune‐killing, and the latter can weaken the immune inhibition to improve the immunotherapeutic efficacy. Meanwhile, the perforation of SLO can promote the delivery of cytokines into the tumor cells to further enhance the efficacy. The designed triply enhanced immunotherapy strategy opens a significant and promising route to promote clinical immunotherapy of cancer.

Abstract This study estimates the timing of unconformity between marine–continental transitional sequence of the Kuldana Formation and continental sequence of the Murree Formation for the first time across the Hazara-Kashmir syntaxis, western Himalaya, Pakistan. The ages of the studied units are constrained using detrital zircon U–Pb geochronology. The maximum depositional ages constrained by weighted mean and youngest detrital zircon age are 37 ± 1.7 Ma and 22.5 ± 0.6 Ma for top of Kuldana and base of Murree formations, respectively. Based on this age, the duration of hiatus is estimated to be ~ 14.5 Ma. The comparison of this unconformity and sedimentation pattern along strike suggests that the initial collision occurred in the central segment causing its early uplift and erosion with development of the unconformity. The sedimentation in the central segment culminated at ~ 37 Ma and resumed at ~ 22.5 Ma. The wider gap in central segment becomes narrower at western and eastern margin suggesting discontinuous deposition due to gradually closure of western and eastern margin. This supports the diachronous collision of the Indian and Asian plates with initial contact at the central segment.

Abstract Rituximab, a chimeric anti-CD20 monoclonal antibody, is an effective treatment for nephrotic syndrome. Hypokalemia is a rare adverse reaction among patients treated with rituximab although there have been extensive reports of acute and chronic adverse events with the administration of rituximab. We herein report two cases of symptomatic hypokalemia after intravenous rituximab administration in our center, to help health professionals consider the possibility of acute hypokalemia after rituximab administration, monitor potassium timely and develop an appropriate treatment plan.

Abstract Background Although immune cells are involved in acute coronary syndrome (ACS), few studies have explored the association of incident ACS with the relative immune cell proportions. We aimed to investigate the association of immune cell proportions with the incidence and risk factors of ACS in the Dongfeng–Tongji cohort. Methods We conducted the analyses with 38,295 subjects from the first follow-up of the Dongfeng–Tongji cohort, including DNA methylation profiles for 1570 individuals. The proportions of immune cell types were observed from routine blood tests or estimated from DNA methylation profiles. For both observed and estimated immune cell proportions, we tested their associations with risk factors of ACS by multivariable linear regression models. In addition, the association of each immune cell proportion with incident ACS was assessed by the Cox regression model and conditional logistic regression model, respectively, adjusting for the risk factors of ACS. Findings The proportions of lymphocytes, monocytes, and neutrophils showed strong associations with sex, followed by diabetes. Moreover, sex and current smoking were the two factors with strongest association with the proportions of lymphocyte subtypes. The hazard ratio (HR) and 95% confidence interval (CI) of incident ACS per standard deviation (SD) increase in proportions of lymphocytes and neutrophils were 0.91 (0.85–0.96) and 1.10 (1.03–1.16), respectively. Furthermore, the OR (95% CI) of incident ACS per SD increase in proportions of NK cells, CD4+ T cells, and B cells were 0.88 (0.78–0.99), 1.15 (1.03–1.30), and 1.13 (1.00–1.26), respectively. Interpretation The proportions of immune cells were associated with several risk factors of ACS, including sex, diabetes, and current smoking. In addition, proportion of neutrophils had a risk effect, while proportion of lymphocytes had a protective effect on the incidence of ACS. The protective effect of lymphocytes was probably driven by NK cells.

Reservoir sensitivity is a parameter that is used to evaluate the degree of change in reservoir permeability under the influence of external fluids. Accurate evaluation of reservoir sensitivity is conducive to the optimization of fluid parameters during exploration and development. Taking the Wenchang Formation and Enping Formation of the Paleogene in the Huilu area of the Pearl River Mouth Basin as the research object, reservoir sensitivity experiments were carried out. Combined with the corresponding experimental results obtained using methods such as thin section identification, scanning electron microscopy (SEM), X-ray diffraction (XRD), mercury intrusion porosimetry (MIP), and screening analysis, based on mineral sensitization and pore structure sensitization, qualitative and quantitative evaluations of reservoir sensitivity were carried out, and factors affecting sensitivity and sensitization mechanisms were analyzed. This work shows the following: (1) The sandstone reservoirs in the two areas have the same clay type, but the total clay content of the Wenchang Formation is greater than that of the Enping Formation. The porosity of the Wenchang Formation is less developed than the Enping Formation. (2) The Wenchang Formation has weak or moderately weak water sensitivity and moderately weak or moderately strong flow velocity sensitivity. The water sensitivity of the Enping Group samples is moderately weak or moderately strong, the flow rate sensitivity is moderately weak, the alkali sensitivity is weak, the acid sensitivity is moderately weak, and the salinity sensitivity is moderately weak or moderately strong. (3) The sensitivity of the Wenchang Formation is mainly affected by the content of clay minerals. The sensitivity of the Enping Formation is also affected by the clay content and type. Although the clay content is not high, the permeability is more susceptible to sensitivity due to the pore structure and debris particle distribution characteristics. These conclusions are beneficial for the selection of fluid parameters and efficient reservoir development.

Untreated or inadequately treated silver−containing wastewater may pose adverse effects on hu−man health and the ecological environment. Currently, significant progress has been made in the treatment of Ag(I) in wastewater using adsorption methods, with adsorbents playing a pivotal role in this process. This paper provides a systematic review of various adsorbents for the recovery and treatment of Ag(I) in wastewater, including MOFs, COFs, transition metal sulfides, metal oxides, biomass materials, and other polymeric materials. The adsorption mechanisms of these materials for Ag(I) are elaborated upon, along with the challenges currently faced. Furthermore, insights into optimizing adsorbents and developing novel adsorbents are proposed in this study.

In order to improve the seismic performance of reinforced concrete (RC) columns, a reinforcement technology using prestressed steel wire ropes embedded in polyurethane cement composite material is proposed. Four concrete columns reinforced with different materials were subjected to a combination of axial compression and horizontally repeated loading tests (one of which was not reinforced, while the remaining three were reinforced with prestressed steel wire rope, polyurethane cement composite material, and prestressed steel wire ropes embedded in polyurethane cement composite material). The experimental results show that the ductility and energy dissipation capacity of reinforced concrete columns after reinforcement are significantly improved. After strengthening with prestressed steel wire ropes embedded in polyurethane cement composite material, the ultimate horizontal displacement and energy dissipation capacity of reinforced concrete columns were significantly improved, which were 69% and 3.2 times higher than those of unreinforced columns, respectively.

Multi-unmanned systems have demonstrated significant applications across various fields under complex or extreme operating environments. In order to make such systems highly efficient and reliable, cooperative decision-making methods have been utilized as a critical technology for successful future applications. However, current multi-agent decision-making algorithms pose many challenges, including difficulties understanding human decision processes, poor time efficiency, and reduced interpretability. Thus, a real-time online collaborative decision-making model simulating human cognition is presented in this paper to solve those problems under unknown, complex, and dynamic environments. The provided model based on the Soar cognitive architecture aims to establish domain knowledge and simulate the process of human cooperation and adversarial cognition, fostering an understanding of the environment and tasks to generate real-time adversarial decisions for multi-unmanned systems. This paper devised intricate forest environments to evaluate the collaborative capabilities of agents and their proficiency in implementing various tactical strategies while assessing the effectiveness, reliability, and real-time action of the proposed model. The results reveal significant advantages for the agents in adversarial experiments, demonstrating strong capabilities in understanding the environment and collaborating effectively. Additionally, decision-making occurs in milliseconds, with time consumption decreasing as experience accumulates, mirroring the growth pattern of human decision-making.

Abstract Objective To explore dermatomyositis signature genes as potential biomarkers of hepatocellular carcinoma and their associated molecular regulatory mechanisms. Methods Based on the mRNA-Seq data of dermatomyositis and hepatocellular carcinoma in public databases, five dermatomyositis signature genes were screened by LASSO regression analysis and support vector machine (SVM) algorithm, and their biological functions in dermatomyositis with hepatocellular carcinoma were investigated, and a nomogram risk prediction model for hepatocellular carcinoma was constructed and its predictive efficiency was initially evaluated. The immune profile in hepatocellular carcinoma was examined based on the CIBERSORT and ssGSEA algorithms, and the correlation between five dermatomyositis signature genes and tumor immune cell infiltration and immune checkpoints in hepatocellular carcinoma was investigated. Results The expression levels of five dermatomyositis signature genes were significantly altered in hepatocellular carcinoma and showed good diagnostic efficacy for hepatocellular carcinoma, suggesting that they may be potential predictive targets for hepatocellular carcinoma, and the risk prediction model based on five dermatomyositis signature genes showed good risk prediction efficacy for hepatocellular carcinoma and has good potential for clinical application. In addition, we also found that the upregulation of SPP1 expression may activate the PI3K/ART signaling pathway through integrin-mediated activation, which in turn regulates the development and progression of hepatocellular carcinoma. Conclusion LY6E, IFITM1, GADD45A, MT1M, and SPP1 are potential predictive targets for new-onset hepatocellular carcinoma in patients with dermatomyositis, and the upregulation of SPP1 expression may activate the PI3K/ART signaling pathway through the mediation of integrins to promote the development and progression of hepatocellular carcinoma.

Abstract The transcription factor hypoxia-inducible factor-1α (HIF-1α), as a master regulator of adaptive responses to hypoxia, possesses two transcriptional activation domains [TAD, N-terminal (NTAD), and C-terminal (CTAD)]. Although the roles of HIF-1α NTAD in kidney diseases have been recognized, the exact effects of HIF-1α CTAD in kidney diseases are poorly understood. Here, two independent mouse models of hypoxia-induced kidney injury were established using HIF-1α CTAD knockout (HIF-1α CTAD−/−) mice. Furthermore, hexokinase 2 (HK2) and mitophagy pathway are modulated using genetic and pharmacological methods, respectively. We demonstrated that HIF-1α CTAD−/− aggravated kidney injury in two independent mouse models of hypoxia-induced kidney injury, including ischemia/reperfusion-induced kidney injury and unilateral ureteral obstruction-induced nephropathy. Mechanistically, we found that HIF-1α CTAD could transcriptionally regulate HK2 and subsequently ameliorate hypoxia-induced tubule injury. Furthermore, it was found that HK2 deficiency contributed to severe renal injury through mitophagy inhibition, while mitophagy activation using urolithin A could significantly protect against hypoxia-induced kidney injury in HIF-1α C-TAD−/− mice. Our findings suggested that the HIF-1α CTAD-HK2 pathway represents a novel mechanism of kidney response to hypoxia, which provides a promising therapeutic strategy for hypoxia-induced kidney injury.

Summary: Slow earthquakes predominant in Costa Rica indicate unstable faulting of segmented Central American megathrusts, but the recurrence of episodic tremors and slips reported to precede a giant earthquake remains still enigmatic. The underlying mechanism is related to the variation in the coupling along the heterogeneous subduction interface which is poorly understood. In this study, we used up-to-date 3D thermal modeling to provide insights into the along-strike variation in the thermal state and hydraulic distribution beneath the Central American subduction zone. Our results show that the subducted Cocos Plate is much warmer than previously estimated, and the slab geometry exhibits remarkable perturbations along the trench. We found that the regions of large dehydration rate along the slab are consistent with the seismicity occurrence depth beneath the Moho. Below the Nicoya Peninsula and the Guatemala-Nicaragua segment of megathrusts, fluids derived from subducted slab result in increased pore fluid pressures and subsequent recurrence of slow slip events and regular earthquakes.

Mulching is an important practice to reduce soil water loss and improve productivity in agriculture. To investigate the influence of dual mulching with crushed wheat straw padding and plastic film combined with different irrigation amounts on soil nutrients and the growth of edible sunflower, a field experiment was conducted in Minqin Experimental Station of Gansu Institute of Hydraulic Sciences from 2016 to 2018. The experiment adopted a two-factor design with four mulching methods: no mulching (N), straw mulching (S) at 4500 kg ha−1, plastic film mulching (F), crushed wheat straw padding and plastic film mulching (SF) at 4500 kg ha−1, and three irrigation levels: high (H=900 m3 ha−1), medium (M=750 m3 ha−1) and low (L=600 m3 ha−1). The results showed that the soil nutrients under the dual mulching of crushed wheat straw padding and plastic film were improved. The soil available phosphorus (AP) content was highest under SFH treatment, varying significantly with treatments (P

Soil erosion is an important cause of global land degradation and other ecological and environmental problems. Revealing the influence mechanism of land use/cover change (LUCC) on sediment yield can provide a scientific basis for efficient comprehensive and decision-making management of watersheds. As an important indicator of sediment yield and transport capacity, sediment connectivity has been widely studied in recent years. However, the existing index of sediment connectivity (IC) ignores the influence of upslope land use/cover on confluence and the corresponding changes in downslope sediment transport. Moreover, a formula describing the upslope and downslope components does not establish an effective correlation with existing soil erosion formulas. Therefore, the index is not closely related to the erosion process and does not reflect the physical process of sediment transport and sediment deposition. In addition, there have been few reports concerning the effect of LUCC on sediment connectivity inside (on-site impact) and outside (off-site impact) the changed patches. Consequently, by based on addition of the revised parameters of the effective confluence area (Ar) and the runoff velocity factor (v) of the sediment delivery distributed (SEDD) model, an improved sediment connectivity index (ICZQ) is proposed. The results indicate that ICZQ has a significant linear relationship with annual runoff depth or sediment yield modulus in small watersheds within 100 km2 in the Loess Plateau, except for feature years containing rainstorm events (daily rainfall exceeding 50 mm). Therefore, the runoff and sediment transport capacity of small watersheds can be characterized by ICZQ under the influence of LUCC and rainfall change. In 1982–2020, driven by LUCC with an enhancement in vegetation (forest and grass), the ICZQ decreased in 90% of the area and decreased by a significant or extremely significant level over 48% of the area. To better understand the effects of LUCC on sediment connectivity, we analyzed on-site and off-site impacts with rainfall remaining unchanged to control the variables. The contribution rates of the on-site and off-site impacts caused by LUCC on sediment connectivity in Lvergou were 61% and 39%, 48% and 52%, respectively, over two typical periods (1985–1990 and 2015–2020). Due to the large proportion that off-site impacts occupied in the sediment connectivity change, the impact of LUCC on sediment connectivity cannot be ignored, especially when the associated scale is relatively small. The present study provides a quantitative method for the optimization of land use/cover patterns, such as vegetation restoration in watersheds along with a reference for further revealing the impact mechanism of erosion and sediment yield in watersheds.

Abstract Sperm selection is an essential component of all assisted reproductive treatments (ARTs) and is by far the most neglected step in the ART workflow in regard to technological innovation. Conventional sperm selection methodologies typically produce a higher total number of sperm with variable motilities, morphologies, and levels of DNA integrity. Gold-standard techniques, including density gradient centrifugation (DGC) and swim-up (SU), have been shown to induce DNA fragmentation through introducing reactive oxygen species (ROS) during centrifugation. Here, we demonstrate a 3D printed, biologically inspired microfluidic sperm selection device (MSSP) that utilizes multiple methods to simulate a sperms journey toward selection. Sperm are first selected based on their motility and boundary-following behavior and then on their expression of apoptotic markers, yielding over 68% more motile sperm than that of previously reported methods with a lower incidence of DNA fragmentation and apoptosis. Sperm from the MSSP also demonstrated higher motile sperm recovery after cryopreservation than that of SU or neat semen. Experiments were conducted side-by-side against conventional SU methods using human semen (n = 33) and showed over an 85% improvement in DNA integrity with an average 90% reduction in sperm apoptosis. These results that the platform is easy-to-use for sperm selection and mimics the biological function of the female reproductive tract during conception.

The element geochemical characteristics and diagenetic alteration products of tuffaceous components in sandstone reservoirs of Paleogene Wenchang Formation in typical subsags of the Huizhou-Lufeng area of the Zhu I Depression, Pearl River Mouth Basin, were identified through microscopic analysis and quantitative analysis of main and trace elements. The impacts of dissolution of different tuffaceous components on physical properties of reservoirs were discussed through quantitative characterization of reservoir physical properties. The results show that there are mainly four types of tuffaceous components in the study area, which are acidic, intermediate, basic and alkaline tuffaceous components. The acidic tuffaceous components evolved in a process of strong alteration and weak dissolution of alteration products, with a large amount of kaolinite precipitated during alteration to disenable the improvement of porosity and permeability. The intermediate and alkaline tuffaceous components evolved in a process of strong dissolution of tuffaceous components and strong alteration of residual tuffaceous components; the dissolution of tuffaceous components created intergranular pores, but the alteration products such as autogenic quartz, apatite and illite deteriorated the pore structure; ultimately, the dissolution of tuffaceous components resulted in the increase of porosity but no increase of permeability of the reservoir. The basic tuffaceous components dominantly evolved in a process of dissolution of tuffaceous components to strong dissolution of alteration products; both tuffaceous components between particles and laumontite generated from alteration can be strongly dissolved to create pores; thus, the dissolution of tuffaceous components can significantly increase the physical properties of the reservoir.

Abstract Tumor extracellular matrix (ECM) not only forms a physical barrier for T cells infiltration, but also regulates multiple immunosuppressive pathways, which is an important reason for immunotherapy failure. The cyclic guanosine monophosphate‐adenosine monophosphate synthase‐stimulator of interferon genes (cGAS‐STING) pathway plays a key role in activating CD8+ T cells, maintaining CD8+ T cells stemness and enhancing the antitumor effect. Herein, a zinc‐organometallic framework vaccine (ZPM@OVA‐CpG) prepared by self‐assembly, which achieves site‐directed release of Zn2+ in dendritic cell (DC) lysosomes and tumor microenvironment under acidic conditions, is reported. The vaccine actively targets DC, significantly enhances cGAS‐STING signal, promotes DC maturation and antigen cross‐presentation, and induces strong activation of CD8+ T cells. Meanwhile, the vaccine reaches the tumor site, releasing Zn2+, significantly up‐regulates the activity of matrix metalloproteinase‐2, degrades various collagen components of tumor ECM, effectively alleviates immune suppression, and significantly enhances the tumor infiltration and killing of CD8+ T cells. ZPM@OVA‐CpG vaccine not only solves the problem of low antigen delivery efficiency and weak CD8+ T cells activation ability, but also achieves the degradation of tumor ECM via the vaccine for the first time, providing a promising therapeutic platform for the development of efficient novel tumor vaccines.

Oilseed rape (Brassica napus L.) is highly susceptible to infection from the soilborne pathogen Plasmodiophora brassicae Woronin that causes clubroot disease and deleteriously affects production throughout the world. In this study, biological control resources were explored by isolating 237 strains of bacteria from fields of oilseed rape using the gradient dilution coating method. A strain with strong antagonistic ability was screened using a plate confrontation test and designated X216. It was identified as Streptomyces melanosporofaciens owing to its morphological characteristics and 16S rRNA gene sequence. This study also examined the lethality of strain X216 to the resting spores of P. brassicae, its influence on infection in root hairs, and its ability to control clubroot on oilseed rape. The corrected lethality rate on resting spores after strain X216 had been used for 14 days was 56.59% ± 1.97%, which was significantly higher than the use of 75% of the fungicides chlorothalonil WP and 20% Fluazinam SC. Significantly fewer root hairs were infected after this treatment. A pot test showed that X216 was 62.14% effective at controlling the disease, which was not significantly different from that of the fungicide 100 g L−1 cyazofamid SC diluted 1,000-fold but significantly higher than those of 75% chlorothalonil and 50% carbendazim WP. Strain X216 controlled 43.16% of the incidence of clubroot in the field, which could significantly reduce the disease index of oilseed rape clubroot. Therefore, strain X216 is promising to study for the biological control of oilseed rape clubroot.

Cardiac hypertrophy is frequently associated with ventricular dysfunction and heart failure. Paeoniflorin, has been widely used to treat cardiovascular dysfunction-related diseases. However, the underlying mechanism has been unclear. Here, we investigated the potential inhibitory effects and mechanism of paeoniflorin on oxidative stress of cardiac hypertrophy induced by angiotensin II (AngII) in vitro. Using MTS assay, qRT-PCR, WGA staining assay, and western blot, different dosages (50–400 μM) of paeoniflorin were utilized to examine the antihypertrophy effects on H9c2 cells. Western blot examination revealed the presence of apoptosis-related proteins Bax, Bcl2, and Cytc, antioxidative stress-related proteins Nrf2, HO-1, SOD, and CAT, and mitophagy-related proteins PINK1 and Parkin. qRT-PCR was used to detect the mRNA expression of Bax, Bcl2, Nrf2, and HO-1. TUNEL, caspase3/9 enzyme viability, and MDA, T-AOC, and superoxide levels were all evaluated using commercial kits.The fluorescent probes DCFH-DA and JC-1 were employed to measure cellular ROS and MMP levels. Nrf2 siRNA was utilized to investigate Nrf2's role in paeoniflorin-treated cardiac hypertrophy. Paeoniflorin dramatically reduced cell section area (CSA) and hypertrophic marker (ANP, BNP) expression while inhibiting oxidative stress by modulating ROS and MDA, CAT, SOD, and T-AOC levels. Furthermore, in AngII-induced cardiomyocyte hypertrophy, paeoniflorin restores H9c2 apoptosis by restoring Bax, Bcl-2 Cyt-C, Caspase 3, and Caspase 9 levels. Paeoniflorin also restored Nrf2/HO-1 and PINK1/Parkin expression, and its anti-AngII activities were mediated by Nrf2, which was regulated by Nrf2 knockdown. In conclusion, Our data confirm that paeoniflorin alleviates cardiac hypertrophy through modulating oxidative stress and Nrf2 signaling pathway in vitro.

Summary: Previous subduction thermal models are inconsistent with the values of forearc heat flow (50–140 mW/m2) and global P‒T conditions of exhumed rocks, both suggesting a shallow environment 200–300°C warmer than model predictions. Here, we revaluate these problems in Kuril-Kamchatka using 3D thermomechanical modeling that satisfies the observed subduction history and slab geometry, while our refined 3D slab thermal state is warmer than that predicted by previous 2D models and better matches observational constraints. We show that warmer slabs create hierarchical slab dehydration fronts at various forearc depths, causing fast and slow subduction earthquakes. We conclude that fast-to-slow subduction earthquakes all play a key role in balancing plate coupling energy release on megathrusts trenchward of high P-T volcanism.