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The lithofacies and thermal maturity of the over-mature Lower Cambrian marine shale in the Northern Guizhou Region, and their impacts on reservoir properties in this shale were analyzed by combining geochemistry, mineralogy, and gas adsorption methods. Ten lithofacies were identified, and the dominant lithofacies in the studied shale are lean-total organic carbon (TOC) argillaceous-rich siliceous shale (LTAS), medium-TOC siliceous shale (MTSS), and rich-TOC siliceous shale (RTSS). Since the gas generation potential of organic matter was weak, meso- and macro-pores were compressed or filled during the thermal evolution stage with a vitrinite reflectance (RO) range of 3.0%–4.0%. The controlling factors for methane adsorption capacity in the shale samples are significantly influenced by TOC content rather than thermal maturity. Among the RTSS, MTSS, and LTAS samples, RTSS exhibits the highest favorability for preserving hydrocarbon gas, followed by MTSS. The shale types in this study play a significant role in determining the properties of shale reservoirs, serving as an effective parameter for evaluating shale gas development potential. The RTSS and MTSS with a RO range of 2.0%–3.0% stand out as the most favorable target shale types for shale gas exploration and development.

Abstract The development of coalbed methane (CBM) in China is susceptible to the influence of microstructure. Therefore, it is crucial to understand the extension laws of hydraulic fractures and engineering responses in coal reservoirs affected by microstructure development. Utilizing the Dahebian block in western Guizhou as the study area, this investigation examines the coal reservoir characteristics, fracturing, and drainage engineering analysis of the well DC1 group in the region. The aim is to discuss the spatial distribution characteristics of hydraulic fractures, geological controlling factors influenced by microstructure, and their corresponding engineering responses. The results indicate that, for coal reservoirs unaffected by microstructure, the extension laws of the fracture network in both longitudinal and planar directions are influenced by burial depth and the regional stress field. In the microstructural belt, tectonic stress dominates, causing changes in the ground stress field. Consequently, the hydraulic fracture network deviates from the direction of the maximum principal stress during the extension process. When a secondary fracture is nearby, the hydraulic fracture network extends towards the shortest path radial secondary fracture direction, leading to a rapid increase in fracture width per unit length until it intersects with the secondary fracture. Additionally, the presence of secondary joints near the microfault structure decreases fracturing pressure and results in a dense distribution of the fracture network. This promotes the formation of a complex fracture network, favorable for fracturing. The extension of the fracture network in complex structural development areas is influenced by the microfault structure between wells, which is reflected in the fracturing construction pressure and fluid output. This accounts for the significant variations in the early drainage performance of CBM wells.

The Chinese medicine residue (CMR) is composed of wet substances, so using hydrothermal carbonization (HTC) to recover renewable energy from the residue is a suitable treatment method. Chromium (Cr), a kind of heavy metal element, is enriched in hydrochar and severely restricts its effective utilization. An in-depth analysis of the migration path and mechanism of Cr in hydrochar is helpful in promoting energy utilization for CMR. Here, licorice, a significant Chinese medicine, was selected as the example to analyze the evolutions of its pore and chemical structures and their effects on the migration mechanism of Cr during the HTC process. The products obtained under various HTC conditions were analyzed using nitrogen adsorption, FTIR, and 13C NMR. The results show that, considering reaction time and relevant reactions as the primary factors during the HTC process, the migration pathway of Cr in hydrochar undergoes two stages, and they are the accompanying migration stage and the recovery aggregation stage. Active adsorption sites for Cr may exist within the pore structure of hydrochar. In the HTC process, hydrolysis, decarboxylation, and decarbonylation reactions are the direct drivers of Cr migration, while aromatization is the underlying cause of Cr recovery and aggregation. It is hypothesized that Cr catalyzes the acetylene cyclotrimerization reaction, thereby promoting the formation of aromatic structures in hydrochar and integrating into the hydrochar carbon skeleton.

Abstract Community-acquired respiratory infection is the commonest cause of sepsis presenting to emergency departments. Yet current experimental animal models simulate peritoneal sepsis with intraperitoneal (I.P.) injection of lipopolysaccharide (LPS) as the predominant route. We aimed to compare the progression of organ injury between I.P. LPS and intranasal (I.N.) LPS in order to establish a better endotoxemia murine model of respiratory sepsis. Eight weeks old male BALB/c mice received LPS-Escherichia coli doses at 0.15, 1, 10, 20, 40 and 100 mg per kg body weight (e.g. LPS-10 is a dose of 10 mg/kg body weight). Disease severity was monitored by a modified Mouse Clinical Assessment Score for Sepsis (M-CASS; range 0–21). A M-CASS score ≥ 10 or a weight reduction of ≥ 20%, was used as a criterion for euthanasia. The primary outcome was the survival rate (either no death or no need for euthanasia). The progression of disease was specified as M-CASS, body weight, blood glucose, histopathological changes to lung, liver, spleen, kidney, brain and heart tissues. Survival rate in I.P. LPS-20 mice was 0% (2/3 died; 1/3 euthanized with M-CASS > 10) at 24 h. Survival rate in all doses of I.N. LPS was 100% (20/20; 3–4 per group) at 96 h. 24 h mean M-CASS post-I.P. LPS-10 was 6.4/21 significantly higher than I.N. LPS-10 of 1.7/21 (Unpaired t test, P

Background Vascular smooth muscle cell (VSMC) proliferation is involved in many types of arterial diseases, including neointima hyperplasia, in which Ca2+ has been recognized as a key player. However, the physiological role of Ca2+ release via inositol 1,4,5‐trisphosphate receptors (IP3Rs) from endoplasmic reticulum in regulating VSMC proliferation has not been well determined. Methods and Results Both in vitro cell culture models and in vivo mouse models were generated to investigate the role of IP3Rs in regulating VSMC proliferation. Expression of all 3 IP3R subtypes was increased in cultured VSMCs upon platelet‐derived growth factor‐BB and FBS stimulation as well as in the left carotid artery undergoing intimal thickening after vascular occlusion. Genetic ablation of all 3 IP3R subtypes abolished endoplasmic reticulum Ca2+ release in cultured VSMCs, significantly reduced cell proliferation induced by platelet‐derived growth factor‐BB and FBS stimulation, and also decreased cell migration of VSMCs. Furthermore, smooth muscle–specific deletion of all IP3R subtypes in adult mice dramatically attenuated neointima formation induced by left carotid artery ligation, accompanied by significant decreases in cell proliferation and matrix metalloproteinase‐9 expression in injured vessels. Mechanistically, IP3R‐mediated Ca2+ release may activate cAMP response element–binding protein, a key player in controlling VSMC proliferation, via Ca2+/calmodulin‐dependent protein kinase II and Akt. Loss of IP3Rs suppressed cAMP response element–binding protein phosphorylation at Ser133 in both cultured VSMCs and injured vessels, whereas application of Ca2+ permeable ionophore, ionomycin, can reverse cAMP response element–binding protein phosphorylation in IP3R triple knockout VSMCs. Conclusions Our results demonstrated an essential role of IP3R‐mediated Ca2+ release from endoplasmic reticulum in regulating cAMP response element–binding protein activation, VSMC proliferation, and neointima formation in mouse arteries.

ABSTRACT Current microbiome signatures for chronic diseases such as diabetic kidney disease (DKD) are mainly based on low-resolution taxa such as genus or phyla and are often inconsistent among studies. In microbial ecosystems, bacterial functions are strain specific, and taxonomically different bacteria tend to form co-abundance functional groups called guilds. Here, we identified guild-level signatures for DKD by performing in-depth metagenomic sequencing and conducting genome-centric and guild-based analysis on fecal samples from 116 DKD patients and 91 healthy subjects. Redundancy analysis on 1,543 high-quality metagenome-assembled genomes (HQMAGs) identified 54 HQMAGs that were differentially distributed among the young healthy control group, elderly healthy control group, early-stage DKD patients (EDG), and late-stage DKD patients (LDG). Co-abundance network analysis classified the 54 HQMAGs into two guilds. Compared to guild 2, guild 1 contained more short-chain fatty acid biosynthesis genes and fewer genes encoding uremic toxin indole biosynthesis, antibiotic resistance, and virulence factors. Guild indices, derived from the total abundance of guild members and their diversity, delineated DKD patients from healthy subjects and between different severities of DKD. Age-adjusted partial Spearman correlation analysis showed that the guild indices were correlated with DKD disease progression and with risk indicators of poor prognosis. We further validated that the random forest classification model established with the 54 HQMAGs was also applicable for classifying patients with end-stage renal disease and healthy subjects in an independent data set. Therefore, this genome-level, guild-based microbial analysis strategy may identify DKD patients with different severity at an earlier stage to guide clinical interventions.IMPORTANCETraditionally, microbiome research has been constrained by the reliance on taxonomic classifications that may not reflect the functional dynamics or the ecological interactions within microbial communities. By transcending these limitations with a genome-centric and guild-based analysis, our study sheds light on the intricate and specific interactions between microbial strains and diabetic kidney disease (DKD). We have unveiled two distinct microbial guilds with opposite influences on host health, which may redefine our understanding of microbial contributions to disease progression. The implications of our findings extend beyond mere association, providing potential pathways for intervention and opening new avenues for patient stratification in clinical settings. This work paves the way for a paradigm shift in microbiome research in DKD and potentially other chronic kidney diseases, from a focus on taxonomy to a more nuanced view of microbial ecology and function that is more closely aligned with clinical outcomes.

Objective: This study aimed to evaluate the effect of case-based learning (CBL) method with virtual reality (VR) simulation technology (CBL-VR) on midwifery laboratory courses. Methods: A quasi-experimental design was employed. A total of 135 midwifery students were recruited from Nursing College of Guilin Medical University in China from September 2020 to January 2022. Intervention group recruited students from the Class of 2019 (n = 59) and control group recruited students from the Class of 2018 (n = 76). The intervention group students received the CBL-VR method based on traditional laboratory teaching, the contents of course included four sections: eutocia (6 class hours), dystocia (6 class hours), umbilical cord prolapse (2 class hours), and neonatal asphyxia and resuscitation (4 class hours), 40 min per class hour. The control group students received the traditional laboratory teaching. Students’ academic performance, Self-Directed Learning (SDL) Ability Questionnaire, and the education satisfaction questionnaire were used to evaluate the teaching efficacy between two groups. Results: After intervention, the intervention group students achieved higher scores than the control group in individual operation ability (90.88 ± 2.14 vs. 89.24 ± 3.15), team operation ability (90.97 ± 2.33 vs. 81.28 ± 5.45), and midwifery case analysis ability (88.64 ± 3.19 vs. 86.70 ± 2.56) (P ＜0.01). Prior to the implementation of the course, there was no difference in the SDL ability scores between the two groups of students (P ＞ 0.05). However, following the course intervention, the SDL ability scores of the intervention group were higher than those of the control group (94.78 ± 6.59 vs. 88.12 ± 8.36), and the scores in all dimensions of the intervention group were also higher (P

Abstract A complete blood count (CBC) is routinely ordered for emergency department (ED) patients with infections. Certain parameters, such as the neutrophil-to-lymphocyte ratio (NLR), might have prognostic value. We aimed to evaluate the prognostic value of the presenting CBC parameters combined with clinical variables in predicting 30-day mortality in adult ED patients with infections using an artificial neural network (ANN). We conducted a retrospective study of ED patients with infections between 17 December 2021 and 16 February 2022. Clinical variables and CBC parameters were collected from patient records, with NLR, monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) calculated. We determined the discriminatory performance using the area under the receiver operating characteristic curve (AUROC) and performed a 70/30 random data split and supervised ANN machine learning. We analyzed 558 patients, of whom 144 (25.8%) had sepsis and 60 (10.8%) died at 30 days. The AUROCs of NLR, MLR, PLR, and their sum were 0.644 (95% CI 0.573–0.716), 0.555 (95% CI 0.482–0.628), 0.606 (95% CI 0.529–0.682), and 0.610 (95% CI 0.534–0.686), respectively. The ANN model based on twelve variables including clinical variables, hemoglobin, red cell distribution width, NLR, and PLR achieved an AUROC of 0.811 in the testing dataset.

Necroptosis is a type of regulated cell death (RCD) that is triggered by changes in the extracellular or intracellular milieu that are picked up by certain death receptors. Thanks to its potent capacity to induce immunological responses and overcome apoptotic resistance, it has garnered significant attention as a potential cancer treatment. Basic information for the creation of nano-biomedical treatments is provided by studies on the mechanisms underlying tumor necroptosis. Receptor-interacting protein kinase 1 (RIPK1)–RIPK3-mediated necroptosis, Toll-like receptor domain-containing adapter-inducing interferon (IFN)-β (TRIF)–RIPK3-mediated necroptosis, Z-DNA-binding protein 1 (ZBP1)–RIPK3-mediated necroptosis, and IFNR-mediated necroptosis are the four signaling pathways that collectively account for triggered necroptosis in this review. Necroptosis has garnered significant interest as a possible cancer treatment strategy because, in contrast to apoptosis, it elicits immunological responses that are relevant to therapy. Thus, a thorough discussion is held on the connections between tumor cell necroptosis and the immune environment, cancer immunosurveillance, and cells such as dendritic cells (DCs), cytotoxic T cells, natural killer (NK) cells, natural killer T (NKT) cells, and their respective cytokines. Lastly, a summary of the most recent nanomedicines that cause necroptosis in order to cause immunogenic cell death is provided in order to emphasize their promise for cancer immunotherapy.

PurposeThis study aimed to investigate the composition of ocular surface microbiota in patients with obesity.MethodsThis case-control study, spanning from November 2020 to March 2021 at Henan Provincial People’s Hospital, involved 35 patients with obesity and an equivalent number of age and gender-matched healthy controls. By employing 16S rRNA sequencing, this study analyzed the differences in ocular surface microbiota between the two groups. The functional prediction analysis of the ocular surface microbiota was conducted using PICRUSt2.ResultsThe alpha diversity showed no notable differences in the richness or evenness of the ocular surface microbiota when comparing patients with obesity to healthy controls (Shannon index, P=0.1003). However, beta diversity highlighted significant variances in the microbiota composition of these two groups (ANOSIM, P=0.005). LEfSe analysis revealed that the relative abundances of Delftia, Cutibacterium, Aquabacterium, Acidovorax, Caulobacteraceae unclassified, Comamonas and Porphyromonas in patients with obesity were significantly increased (P

We analyzed a large amount of published petrological, mineralogical, and geochemical data from the Niutitang, Wufeng-Longmaxi, Dawuba, Liangshan, and Longtan organic-rich shales. These include marine shales and marine-continental transitional shales. The main marine organic-rich shales include the Niutitang, Wufeng-Longmaxi, and Dawuba shales, while the main marine-continental organic-rich transitional shales include the Liangshan and Longtan shales. The marine organic-rich shales were generally deposited under anoxic conditions, and are generally brittle siliceous-rich lithofacies, which is a type I organic-matter dominated. In contrast to the marine organic-rich shales, the marine-continental transitional organic-rich shales were most likely deposited under dysoxic to oxic conditions. They are generally less brittle argillaceous-rich lithofacies, that are type III organic-matter dominated. Of the five organic-rich shales, the Niutitang and Wufeng-Longmaxi organic-rich shales are over-mature shales, and the Dawuba, Liangshan, and Longtan organic-rich shales are high-maturity to over-mature shales. The spots with siliceous rock floor on the western edge of the Xuefeng uplift is a favorable area for future exploration of shale gas in the Niutitang organic-rich shale. The Chishui terrestrial basin and center of the aulacogen are the faverable areaa for shale gas expolation and development of the Wufeng-Longmaxi and Dawuba organic-rich shales, respectively. More basic geological research work is needed to select favorable areas for the Liangshan and Longtan organic-rich shales. To accurately guide future shale gas exploration and development, more research is needed on the relationship between the sedimentary environment, the lithofacies, and the reservoir properties of the shales.

Randomness and fluctuations in wind power output may cause changes in important parameters (e.g., grid frequency and voltage), which in turn affect the stable operation of a power system. However, owing to external factors (such as weather), there are often various anomalies in wind power data, such as missing numerical values and unreasonable data. This significantly affects the accuracy of wind power generation predictions and operational decisions. Therefore, developing and applying reliable wind power interpolation methods is important for promoting the sustainable development of the wind power industry. In this study, the causes of abnormal data in wind power generation were first analyzed from a practical perspective. Second, an improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN) method with a generative adversarial interpolation network (GAIN) network was proposed to preprocess wind power generation and interpolate missing wind power generation sub-components. Finally, a complete wind power generation time series was reconstructed. Compared to traditional methods, the proposed ICEEMDAN-GAIN combination interpolation model has a higher interpolation accuracy and can effectively reduce the error impact caused by wind power generation sequence fluctuations

Abstract Vocal communication is essential for social behaviors in humans and non-human primates. While the frontal cortex is crucial to human speech production, its role in vocal production in non-human primates has long been questioned. It is unclear whether activities in the frontal cortex represent diverse vocal signals used in non-human primate communication. Here we studied single neuron activities and local field potentials (LFP) in the frontal cortex of male marmoset monkeys while the animal engaged in vocal exchanges with conspecifics in a social environment. We found that both single neuron activities and LFP were modulated by the production of each of the four major call types. Moreover, neural activities showed distinct patterns for different call types and theta-band LFP oscillations showed phase-locking to the phrases of twitter calls, suggesting a neural representation of vocalization features. Our results suggest important functions of the marmoset frontal cortex in supporting the production of diverse vocalizations in communication.

Abstract Background Infections caused by multidrug resistant bacterial pathogens have been recognized as major global healthcare threat to medicinal, agricultural and pharmaceutical industries by World Health Organization. In this regard, the present study was aimed to isolate endophytes from medicinal plant Polygonatum sibiricum (P. sibiricum) and to investigate their antibacterial efficacy, radical scavenging ability and chemical fingerprinting using Gas Chromatography–Mass Spectrum (GC–MS) analysis. Results Two endophytic fungi Talaromyces assiutensis HJ.14 (T. assiutensis) and Fusarium oxysporum HJ.15 (F. oxysporum) were isolated and identified from the rhizomes of P. sibiricum. Among the extracts screened, ethyl acetate extract of F. oxysporum HJ.15 showed maximum antibacterial activity with the zones of inhibition ranging from 10.98 ± 0.19 to 15.66 ± 1.49 mm and the MIC values ranging from 0.24 to 1.88 µg/mL against the tested bacterial pathogens. In addition, it showed significant antioxidant activity with EC50 values of 6.21–17.97 µg/mL. Further, GC–MS analysis revealed the presence of propanoic acid ethyl ester, hexadecanoic acid methyl ester, hexadecanoic acid ethyl ester, 9-Octadecenoic acid (Z)-methyl ester, 1-Octanol, 2-Undecenal, butanoic acid, 3-hydroxy- and hexanoic acid were the most abundant compounds in the active crude extract which was responsible for the significant antibacterial and antioxidant properties. Conclusions In summary, our results clearly suggest that the F. oxysporum HJ.15 will be a promising starting point for the isolation of active antibacterial compounds with antioxidant properties.

Conclusion: Our findings provide compelling causal genetic evidence for the bidirectional crosstalk between specific GM taxa and DKD development, contributing valuable insights for a comprehensive understanding of the pathological mechanisms of DKD and highlighting the possibility of prevention and management of DKD by targeting GM.

The disruption and reconstruction of the TREM2+ tissue resident macrophage (TRM) barrier on the surface of synovial lining play a key role in the activation and "remission" of rheumatoid arthritis (RA), which engender the prediction of this immunologic barrier as a potential driver for the achievement of "cure" in RA. However, strategies to promote the reconstruction of this barrier have not been reported, and the effect of patching this barrier remains unidentified. On the other hand, appropriate piezoelectric stimulation can reprogram macrophages, which has never been exerted on this barrier TRM yet. Herein, we design piezoelectric tetragonal BaTiO3 (BTO) ultrasound-driven nanorobots (USNRs) by the solvothermal synthesis method, which demonstrates satisfactory electro-mechanical conversion effects, paving the way to generate controllable electrical stimulation under ultrasound to reprogram the barrier TRM by minimally invasive injection into joint cavity. It is demonstrated that the immunologic barrier could be patched by this USNR effectively, thereby eliminating the hyperplasia of vessels and nerves (HVN) and synovitis. Additionally, TREM2 deficiency serum-transfected arthritis (STA) mice models are applied and proved the indispensable role of TREM2 in RA curing mediated by USNR. In all, our work is an interesting and important exploration to expand the classical tetragonal BTO nanoparticles in the treatment of autoimmune diseases, providing a new idea and direction for the biomedical application of piezoelectric ceramics.

Abstract Background Various bacteria and archaea, including halophilic archaeon Halobacterium sp. NRC-1 produce gas vesicle nanoparticles (GVNPs), a unique class of stable, air-filled intracellular proteinaceous nanostructures. GVNPs are an attractive tool for biotechnological applications due to their readily production, purification, and unique physical properties. GVNPs are spindle- or cylinder-shaped, typically with a length of 100 nm to 1.5 μm and a width of 30–250 nm. Multiple monomeric subunits of GvpA and GvpC proteins form the GVNP shell, and several additional proteins are required as minor structural or assembly proteins. The haloarchaeal genetic system has been successfully used to produce and bioengineer GVNPs by fusing several foreign proteins with GvpC and has shown various applications, such as biocatalysis, diagnostics, bioimaging, drug delivery, and vaccine development. Results We demonstrated that native GvpC can be removed in a low salt buffer during the GVNP purification, leaving the GvpA-based GVNP's shell intact and stable under physiological conditions. Here, we report a genetic engineering and chemical modification approach for functionalizing the major GVNP protein, GvpA. This novel approach is based on combinatorial cysteine mutagenesis within GvpA and genetic expansion of the N-terminal and C-terminal regions. Consequently, we generated GvpA single, double, and triple cysteine variant libraries and investigated the impact of mutations on the structure and physical shape of the GVNPs formed. We used a thiol–maleimide chemistry strategy to introduce the biotechnological relevant activity by maleimide-activated streptavidin–biotin and maleimide-activated SpyTag003-SpyCatcher003 mediated functionalization of GVNPs. Conclusion The merger of these genetic and chemical functionalization approaches significantly extends these novel protein nanomaterials' bioengineering and functionalization potential to assemble catalytically active proteins, biomaterials, and vaccines onto one nanoparticle in a modular fashion. Graphical Abstract

Abstract Background Reporting quality is a critical issue in health sciences. Adopting the reporting guidelines has been approved to be an effective way of enhancing the reporting quality and transparency of clinical research. In 2012, we found that only 7 (7/1221, 0.6%) journals adopted the Consolidated Standards of Reporting Trials (CONSORT) statement in China. The aim of the study was to know the implementation status of CONSORT and other reporting guidelines about clinical studies in China. Methods A cross-sectional bibliometric study was conducted. Eight medical databases were systematically searched, and 1039 medical journals published in mainland China, Hong Kong, Macau, and Taiwan were included. The basic characteristics, including subject, language, publication place, journal-indexed databases, and journal impact factors were extracted. The endorsement of reporting guidelines was assessed by a modified 5-level evaluation tool, namely i) positive active, ii) positive weak, iii) passive moderate, iv) passive weak and v) none. Results Among included journals, 24.1% endorsed CONSORT, and 0.8% endorsed CONSORT extensions. For STROBE (STrengthening the Reporting of Observational Studies in Epidemiology), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), STARD (An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies), CARE (CAse REport guidelines), the endorsement proportion were 17.2, 16.6, 16.4, and 14.8% respectively. The endorsement proportion for SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials), TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis), AGREE (Appraisal of Guidelines, Research, and Evaluation), and RIGHT (Reporting Items for Practice Guidelines in Healthcare) were below 0.7%. Conclusions Our results showed that the implementation of reporting guidelines was low. We suggest the following initiatives including i) enhancing the level of journal endorsement for reporting guidelines; ii) strengthening the collaboration among authors, reviewers, editors, and other stakeholders; iii) providing training courses for stakeholders; iv) establishing bases for reporting guidelines network in China; v) adopting the endorsement of reporting guidelines in the policies of the China Periodicals Association (CPA); vi) promoting Chinese medical journals into the international evaluation system and publish in English.

In the current study, a novel intrinsic functionalization approach based on composite feeding additive for silkworms to produce silk fibers (SFs) with enhanced mechanical properties has been successfully developed. Effect of single feeding additive by either nano hydroxyapatite (Nano-HA) or collagen, and composite feeding by both additives on the silkworm larvae growth and cocooning, crystalline structure, molecular conformationas as well as mechanical properties of SFs have been systematically investigated. Experimental results demonstrated that feeding additive strategy could greatly facilitate the growth and cocooning of the silkworms. Surface and cross-section morphology observation suggested the additive has been absorbed into silkworm body and eventually embedded in SFs. Meanwhile, the basic structure of SFs still kept integrity after feeding additive from X-ray diffraction (XRD) analysis. Furthermore, fourier transform infrared (FTIR) spectrum demonstrated that random coil/α-helix and β-sheet content of SFs by feeding additive presented an increase and decrease change than natural SFs. More importantly, mechanical properties of SFs exhibited an obvious enhancement by composite additive than single additive feeding due to the nanoconfined crystallite toughening and polymer physical blending mechanism. Inspired by this approach, the composite additive feeding may open a novel and green strategy to fabricate SFs with enhanced mechanical properties.

Accurately assessing the risk of flash floods is a fundamental prerequisite for defending against flash flood disasters. The existing methods for assessing flash flood risk are constrained by unclear key factors and challenges in elucidating disaster mechanisms, resulting in less-than-ideal early warning effectiveness. This article is based on official statistics of flash flood disaster data from 2017 to 2021. It selects eight categories of driving factors influencing flash floods, such as rainfall, underlying surface conditions, and human activities. Subsequently, a geographical detector is utilized to analyze the explanatory power of each driving factor in flash flood disasters, quantifying the contribution of each factor to the initiation of flash flood; the flash flood potential index (FFPI) was introduced to assess the risk of flash flood disasters in China, leading to the construction of a comprehensive assessment framework for flash flood risk. The results indicate that (1) Flash floods are generally triggered by multiple factors, with rainfall being the most influential factor, directly causing flash floods. Soil type is the second most influential factor, and the combined effects of multiple factors intensify the risk of flash floods. (2) The southeastern, southern, and southwestern regions of China are considered high-risk areas for flash floods, with a high danger level, whereas the northwestern, northern, and northeastern plain regions exhibit a lower danger level. The above research results provide reference and guidance for the prevention and control of flash flood disasters.

Abstract Background Hyperglycaemia in pregnancy (HIP) is a common metabolic disorder that not only poses risks to maternal health but also associates with an increased risk of diabetes among offspring. Vertical transmission of microbiota may influence the offspring microbiome and subsequent glucose metabolism. However, the mechanism by which maternal gut microbiota may influence glucose metabolism of the offspring remains unclear and whether intervening microbiota vertical transmission could be used as a strategy to prevent diabetes in the offspring of mothers with HIP has not been investigated. So we blocked vertical transmission to investigate its effect on glucose metabolism in the offspring. Results We established a murine HIP model with a high-fat diet (HFD) and investigated the importance of vertical transmission of gut microbiota on the glucose metabolism of offspring via birth and nursing by blocking these events through caesarean section (C-section) and cross-fostering. After weaning, all offspring were fed a normal diet. Based on multi-omics analysis, biochemical and transcriptional assays, we found that the glucometabolic deficits in the mothers were subsequently ‘transmitted’ to the offspring. Meanwhile, the partial change in mothers’ gut microbial community induced by HIP could be transmitted to offspring, supported by the closed clustering of the microbial structure and composition between the offspring and their mothers. Further study showed that the microbiota vertical transmission was blocked by C-section and cross-fostering, which resulted in improved insulin sensitivity and islet function of the offspring of the mothers with HIP. These effects were correlated with changes in the relative abundances of specific bacteria and their metabolites, such as increased relative abundances of Bifidobacterium and short-chain fatty acids. In particular, gut microbial communities of offspring were closely related to those of their foster mothers but not their biological mothers, and the effect of cross-fostering on the offspring’s gut microbiota was more profound than that of C-section. Conclusion Our study demonstrates that the gut microbiota transmitted via birth and nursing are important contributors to the glucose metabolism phenotype in offspring. Video Abstract

Complex hierarchical architectures are ubiquitous in natural hard tissues, which comprise an elaborate assembly of hard and soft phases spanning from the nanoscale to the macroscale. The elegant architectures grant unique performance in terms of strength and toughness, but the biomimetic fabrication of synthetic materials with highly consistent structural and mechanical characteristics with natural counterparts remains a great challenge. Here, a centimeter‐size artificial lamellar bone is successfully fabricated for the first time via a well‐orchestrated “multiscale cascade regulation” strategy combining multiple techniques of molecular self‐assembly, electrospinning, and pressure‐driven fusion from molecular to macroscopic levels. The bulk artificial lamellar bone that is composed of hierarchically assembled mineralized collagen fibrils with a waiver of any synthetic polymer highly resembles the chemical composition, multiscale structural organization, and rotated plywood‐like structure of natural lamellae, thus achieving a good combination of lightweight and high‐stiffness (Ey ≈ 15.2 GPa), ‐strength (σf ≈ 118.4 MPa), and ‐toughness (KJC ≈ 9.3 MPa m1/2). This multiscale cascade regulation strategy can break through the limitations of a single technique and enable the construction of elaborate composite materials with multiscale step‐by‐step regulations of hierarchically structural organizations for unique mechanical properties.

Blood biomarkers hold potential for the early diagnosis of ischaemic stroke (IS). We aimed to evaluate the current weight of evidence and identify potential biomarkers and biological pathways for further investigation. We searched PubMed, EMBASE, the Cochrane Library and Web of Science, used R package meta4diag for diagnostic meta-analysis and applied Gene Ontology (GO) analysis to identify vital biological processes (BPs). Among 8544 studies, we included 182 articles with a total of 30,446 participants: 15675 IS, 2317 haemorrhagic stroke (HS), 1798 stroke mimics, 846 transient ischaemic attack and 9810 control subjects. There were 518 pooled biomarkers including 203 proteins, 114 genes, 108 metabolites and 88 transcripts. Our study generated two shortlists of biomarkers for future research: one with optimal diagnostic performance and another with low selection bias. Glial fibrillary acidic protein was eligible for diagnostic meta-analysis, with summary sensitivities and specificities for differentiating HS from IS between 3 h and 24 h after stroke onset ranging from 73% to 80% and 77% to 97%, respectively. GO analysis revealed the top five BPs associated with IS. This study provides a holistic view of early diagnostic biomarkers in IS. Two shortlists of biomarkers and five BPs warrant future investigation.

Abstract The development of antimicrobial fabrics and textiles that can sustainably inhibit a broad spectrum of microbes is crucial for protecting against pathogens in various environments. However, engineering antimicrobial textiles is challenging due to issues with discoloration and inhibited breathability, the use of harmful or harsh reagents and synthesis conditions, and complex and/or time-consuming processing. Herein, we develop a facile and rapid approach to deposit antimicrobial coatings using universally adherent plant polyphenols and antimicrobial silver ions. Importantly, the coatings are colorless, thin (

Bimetallic nanozymes have been emerging as essential catalysts due to their unique physicochemical properties from the monometallics. However, the access to optimize catalytic performance is often limited by the thermodynamic immiscibility and also heterogeneity. Thus, we present a one-step coreduction strategy to prepare the miscible Cu–Pd bimetallic nanozymes with controllable shape and homogeneously alloyed structure. The homogeneity is systematically explored and luckily, the homogeneous introduction of Cu successfully endows Cu–Pd bimetallic nanozymes with enhanced Fenton-like efficiency. Density functional theory (DFT) theoretical calculation reveals that Cu–Pd bimetallic nanozymes exhibit smaller d-band center compared with Pd nanozymes. Easier adsorption of H2O2 molecular contributed by the electronic structure of Cu significantly accelerate the catalytic process together with the strong repulsive interaction between H atom and Pd atom. In vitro cytotoxicity and intracellular ROS generation performance reveal the potential for in vivo biocatalysis. The strategy to construct kinetically miscible Cu–Pd bimetallic nanozymes will guide the development of bimetallic catalysts with excellent Fenton-like efficiency for biocatalytic nanomedicine.

Abstract Lung cancer is the leading cause of cancer deaths worldwide and most cancer patients receiving conventional chemotherapy suffer from severe side effects due to the non‐selective effects of chemotherapeutic drugs on normal cells. Targeted nanomaterials can obtain excellent accumulation at the tumor site through their active or passive targeting mechanisms, thereby reducing the toxicity of the drugs in various ways. In this study, hyaluronic acid (HA) which could specifically bind to CD44 on the surface of tumor cells, was used to modify amine‐caged platinum nanoclusters (Pt NCs‐NH2) to obtain targeting HA‐Pt NCs‐NH2. Based on the differential expression of CD44 on the surface of three lung cells (non‐small cell lung cancer cell H1299, small cell lung cancer cell H446, and embryonic lung fibroblast HFL1), HA‐Pt NCs‐NH2 can differentially enter the three cells and achieve their targeting of non‐small cell lung cancer cell (NSCLC) cells. Pt NCs significantly inhibited the proliferation, migration and invasion of NSCLC cells and induced their apoptosis in comparison of classical cisplatin and carboplatin, showing a bright future in early diagnosis and treatment of NSCLC.

The purpose of this paper is to compare and analyze the electromagnetic characteristics of the basic structure of the coil in the electromagnetic coupling mechanism for the wireless power supply of permanent magnet motors in electric vehicles. The electromagnetic coupling mechanism is one of the key technologies for wireless power transmission and the coil structure plays a key role in the transmission performance of the coupling mechanism, and different structures can achieve different performances. The central objective of coil structure studies is to investigate how the coupling coefficient can be increased to achieve greater transmitted power and higher efficiency. In this paper, we investigate two basic coil configurations, circular and square, by studying their flux density variations when used as transmitting coils and their electromagnetic coupling characteristics when used as receiving coils. Three couplers consisting of circular and square coils are also analyzed in simulations and experiments are carried out on couplings containing circular and square coils of the same area. The results of the study show that the qualitative analysis, simulation analysis and experimental results are in high agreement. The results of this paper are an important reference for the design and optimization of wireless power coils for permanent magnet motors in electric vehicles.

Due to the extremely low porosity and permeability of shale, fracturing is often used to develop shale gas reservoirs. During shale fracturing, extremely high fracturing pressure may invalidate the integrity of the cement sheath and bring hidden dangers to the safe development of shale gas. This paper compares the stress state of the three-dimensional unperforated and perforated finite element models of casing-cement sheath-formation to obtain the influence of perforation on the stress concentration and failure area of the cement sheath. The stress state comparison incorporates three sets of perforation models with different hole densities and diameter verifies the stress concentration law of perforation on the cement sheath. By studying the effects of the elastic modulus and Poisson’s ratio of the cement sheath on the maximum tensile and compressive stresses of the cement sheath under fracturing pressure, the integrity failure form of the cement sheath and the measures for integrity failure are obtained. The results show that the peak stress concentration of the perforated cement sheath is about twice the normal value of the stress. The failure area is the two ends of the perforation, the shape is similar to the bottom surface of the elliptical cone, and the thickness is up to half of the wall thickness of the cement sheath. The line length of the largest failure area is 4.5 times the diameter of the hole. Under fracturing conditions, the cement sheath generally undergoes tensile failure. The lower the elastic modulus and Poisson’s ratio of the cement sheath, the smaller the tensile stress of the cement sheath, and the less likely it is to cause tensile failure.

Many cryogenic electron microscopy (cryo-EM) single particle analyses are constrained by the sample preparation step upon which aggregation, dissociation, and/or preferential orientation of particles can be introduced. Here, we report how we solved these problems in the case of CDC48A, a hexameric AAA ATPase from Arabidopsis thaliana. CDC48A hexamers are well preserved under negative staining conditions but disassemble during grid freezing using the classical blotting method. Vitrification of grids using the blot-free Chameleon method preserved the integrity of particles but resulted in their strong preferential orientation. We then used a strategy where we improved in parallel the purification of CDC48A and the conditions for cryo-EM data acquisition. Indeed, we noted that images taken from thicker ice presented an even distribution of intact particles with random orientations, but resulted in a lower image resolution. Consequently, in our case, distribution, orientation, image resolution, and the integrity of particles were tightly correlated with ice thickness. By combining the more homogeneous and stable CDC48A hexamers resulting from our improved purification protocol with an iterative search across different ice thicknesses, we identified an intermediate thickness that retained sufficiently high-resolution structural information while maintaining a complete distribution of particle orientations. Our approach may provide a simple, fast, and generally applicable strategy to record data of sufficient quality under standard laboratory and microscope settings. This method may be of particular value when time and resources are limited.

With tremendous research advances in biomedical application, liquid metals (LM) also offer fantastic chemistry for synthesis of novel nano-composites. Herein, as a pioneering trial, litchi-shaped heterogeneous eutectic gallium indium-Au nanoparticles (EGaIn-Au NPs), served as effective radiosensitizer and photothermal agent for radio-photothermal cancer therapy, have been successfully prepared using in situ interfacial galvanic replacement reaction. The enhanced photothermal conversion efficiency and boosted radio-sensitization effect could be achieved with the reduction of Au nanodots onto the eutectic gallium indium (EGaIn) NPs surface. Most importantly, the growth of tumor could be effectively inhibited under the combined radio-photothermal therapy mediated by EGaIn-Au NPs. Inspired by this approach, in situ interfacial galvanic replacement reaction may open a novel strategy to fabricate LM-based nano-composite with advanced multi-functionalities.

Summary: Background: The results and data availability of vaccine trials directly affect the decisions of healthcare providers, the public, and policymakers as to whether the vaccine should be applied. However, the reporting and data sharing level of COVID-19 vaccine studies are not clear. Methods: A cross-sectional study was conducted. A systematic search up to 9 May 2021 in 12 databases and an updated search to 6 July 2021 were conducted in the Cochrane Living Systematic Review and Network Meta-Analysis database to identify COVID-19 vaccine trials. The basic characteristics of included trials were summarized. The reporting level was assessed according to the CONSORT checklist. The data sharing level was assessed by open science practices. Types of incomplete reporting including protocol deviation, lack of primary outcomes clarity, and the omission of harms were analyzed. Findings: Finally, thirty-six COVID-19 vaccine articles reporting on 40 randomized controlled trials were included in this analysis. Based on the CONSORT checklist, the mean reporting score was 29.7 [95% confidence interval 28.7, 30.7]. Thirty-one articles (31/36, 86.1%) had data sharing statements, twenty-five articles (25/36, 69.4%) provided access to the source data. Twenty-seven articles (27/36, 75.0%) had protocol deviation, lack of primary outcomes clarity, or the omission of harms. Interpretation: The reporting and data sharing level of COVID-19 vaccine trials were not optimal. We hope that the reporting and data sharing of future trials will be improved. We recommend establishing a comprehensive, accurate data sharing system for future vaccine trials. Funding: This work was supported by the National Key R&D Program of China (2019YFC1710400; 2019YFC1710403).

In the process of shale gas development, different drilling, hydro-fracturing, and pumping speeds will produce different productivity effects. This reflects the effect of the loading rate of rock mechanics. Therefore, it is of great scientific significance to study the deformation and failure characteristics of shale under different loading rates. In order to reveal the loading rate effect of the Longmaxi shale, a series of laboratory experiments were carried out, including scanning electron microscope, XRD, and uniaxial compression tests at different loading rates. The results show that 1) the peak strength and elastic modulus of shale increase with the increase in the loading rate, but Poisson’s ratio has no obvious rule with the increase in the loading rate. In contrast, the loading rate causes the peak strength to vary by about 20%, which is larger than that of the elastic modulus. 2) The loading rate has a significant influence on shale failure. A higher loading rate will lead to severe damage but with simple cracks, whereas a lower loading rate will lead to complex damage of cracks. With the decrease in the strain rate, the length of the failure crack increases greatly. Therefore, a lower strain rate is helpful to form more broken fragments in the shale matrix. 3) By analyzing the relationship between elastic strain energy/dissipated energy and the loading rate, it is found that the elastic strain rate has a preliminary increasing and then a decreasing trend with the loading rate, but the dissipated energy has a decreasing trend with the loading rate. A higher loading rate is helpful to increase the brittleness of the shale, but a lower loading rate is beneficial to forming more cracks and a greater degree of fracture in the shale matrix. The effect of the loading rate on the mechanical properties and fracture properties of the shale is discussed. It is suggested that the lower hydro-fracturing rate is useful for generating more complex crack networks in the shale reservoirs.

Thermostable enzymes have the potential for use in a wide variety of biotechnological applications. Cryo-electron microscopy (cryo-EM) enables the imaging of biomolecules in their native aqueous environment. Here, we present high resolution cryo-EM structures of two thermostable enzymes that exhibit multimeric cage-like structures arranged into two different point-group symmetries. First, we determined the structure of the Sulfur Oxygenase Reductase (SOR) enzyme that catalyzes both the oxygenation and disproportionation of elemental sulfur in Archea and is composed of 24 homomeric units each of MW ≃ 35 kDa arranged in octahedral symmetry. The structure of SOR from Acidianus ambivalens (7X9W) was determined at 2.78 Å resolution. The active site of each subunit inside the central nanocompartment is composed of Fe3+ coordinated to two water molecules and the three amino acids (H86, H90 and E114). Second, we determined the structure of Lumazine Synthase (LS) from Aquifex aeolicus (7X7M) at 2.33 Å resolution. LS forms a cage-like structure consisting of 60 identical subunits each of MW ≃ 15 kDa arranged in a strict icosahedral symmetry. The LS subunits are interconnected by ion-pair network. Due to their thermostability and relatively easy purification scheme, both SOR and LS can serve as a model for the catalytic and structural characterization of biocatalysts as well as a benchmark for cryo-EM sample preparation, optimization of the acquisition parameters and 3D reconstruction.

With the world’s consensus on low-carbon emission reduction, all walks of life have formulated low-carbon development goals. As a high-energy consumption industry, it is urgent for mining industry to implement the development strategy of low-carbon emission reduction. Therefore, this study tries to provide reasonable suggestions and references for the low-carbon development of the mining industry. Firstly, this study analyzes the industry development, energy consumption, and carbon emission of mining industry from 2000 to 2020. Then, using the Tapio theory, this study constructs the analysis model of decoupling between carbon emission of mining industry and industry growth. The analysis method of decoupling state assignment is proposed for the first time in the model. At the same time, the energy efficiency decoupling index and energy structure decoupling index are introduced to explain the causes of carbon emission decoupling. The research shows that the carbon emission of energy consumption in China’s mining industry peaked in 2013, and the energy efficiency decoupling in 2001–2014 is the main driver of carbon emission decoupling. The sharp growth of industrial output value leads to the decoupling of energy efficiency. At present, the improvement of energy efficiency of China’s mining industry faces great resistance. At the same time, the inhibition effect of energy efficiency on carbon emissions is limited, and the energy structure will be the main factor to inhibit carbon emissions.

In recent years, multifunctional platinum nanoclusters (Pt-NCs) as new Pt-based anti-cancer drugs exhibit a promising therapeutic efficiency for several cancer diseases, especially for human pulmonary carcinoma. However, the endocytosis behaviors (like uptake pathway, etc.) and induced apoptosis mechanism of Pt-NCs for drug-resistant non-small cell lung cancer (NSCLC), are still inconclusive. In this research, we explored the endocytic pathway of Pt-NCs in both typical NSCLC A549 cells and cisplatin-resistant A549/Cis cells through qualitative confocal laser scanning microscope (CLSM) measurement and quantitative flow cytometry (FCM) and inductive coupled plasma-optical emission spectroscopy (ICP-OES) analysis, by the means of introducing the specific inhibitors which impede the classical ways of endocytosis. It was found that Pt-NCs dominatingly entered A549 cells via caveolin-mediated endocytosis as well as A549/Cis cells through micropinocytosis approach. Pt-NCs possessed an excellent inhibitory effect on the cell proliferation, migration and invasion, which the cell activity of A549 cells reduced to 14% and that of A549/Cis cells went down about four fifths. Moreover, Pt-NCs treatment increased caspase-3 protein levels and downregulated the expression of c-Myc and Bcl-2, proving the Pt-NCs-induced apoptosis of NSCLC cells was related to c-Myc/p53 and Bcl-2/caspase-3 signal pathways. These results demonstrate the explicit uptake pathway and apoptotic signaling pathway of Pt-NCs for NSCLC, which provides an in-depth and reasonable theoretical basis for the development of new Pt-NCs-based chemotherapeutics in future clinical practice.

As a kind of clean energy, the exploration and development of coalbed methane (CBM) are of great importance and significance. In this paper, the CBM reservoir parameters of a working area in Western Guizhou Province, China, were predicted by using 3D seismic exploration technology, and the sweet-spot area was evaluated based on the prediction results. In terms of data interpretation, while the traditional technology is extended to the study of CBM, new technologies and methods suitable for CBM were also actively explored, especially in the quantitative prediction methods of parameters such as coal seam thickness, CBM content, coal body structure, in situ stress, etc., and a three-highs quantitative prediction technology of CBM sweet spots characterized by high precision, high resolution, and high coincidence was explored, which is based on logging evaluation and petrophysics. In addition, in the comprehensive evaluation of multiparameter sweet spots, the multiparameter weighted step-by-step evaluation method based on inversion was innovatively proposed, which made the prediction of CBM sweet spots more focused, effective, and practical, and the distribution law of sweet spots was more consistent with the geological law, providing enough basis for subsequent well location deployment. Based on this method, the C409 coal seam was selected as the sweet spot.

It remains a challenge to obtain high-resolution structures of molecules smaller than 200 kDa using single particle cryo-EM. Here, the authors apply the Cs-corrector-VPP coupled cryo-EM and solve structures of the 52 kDa streptavidin (SA) protein at near-atomic resolution.

China’s marine-continental transitional facies shale gas resources are abundant with shale gas resources of about 19.8 trillion cubic meters, while the exploration and development of these shale gas resources are still in the initial stage. The Upper Permian Longtan coal series shale is one of the most important transitional shales in the Yangtze platform, China. In this study, the comprehensive methods of mineralogy and organic geochemistry are used to discuss the characteristic of organic matter and sedimentary environment of the Longtan coal series shale in western Guizhou Province, South China. The results show that (1) the total organic carbon (TOC) content of this shale ranges in 0.6%-28.21%, mainly in 3%-12%, indicating a “good-excellent” hydrocarbon source rock, and its vitrinite reflectance (Ro) ranges from 1.48% to 2.93%, indicating a high-overmature organic matter; (2) the organic matter in this shale is multiorigin, and most of them come from the terrestrial higher plant while the rest come from the plankton; (3) type index (TI) of organic matter is from -65 to 41, indicating most of the kerogens which are II1-III types; and (4) the sedimentary environment of this shale is dominated by suboxic-anoxic fresh water environment, which provides a favorable condition for the preservation of organic matter. In addition, the warm and humid climate during the Late Permian in the Yangtze platform promotes plant growth, and as a result, the Longtan coal series shale is rich in organic matter and has great potential of shale gas exploration and development.

Background: Recently, the incidence of hematological malignancy, such as various leukemias, multiple myeloma and lymphoma, has revealed an increasing tendency, exhibiting a major impact on human health. Most of the available anti-cancer drugs, however, possess high non-targeted accumulation, dosage-associated toxicity, fast elimination, and lack specificity towards tumors, which restrict their utilization in clinical therapy. This extends also to cancer diagnosis where there is a lack of predictive biomarkers. Object: Noble metal nanomaterials (NM NMs) have the potential to overcome these shortcomings due to several characteristics including ease of synthesis, ultra-small size, easy surface modification and specific physicochemical properties. At present, gold-, silver- and platinum-based nanomaterials have been employed in the tracing and treatment of hematopoietic tumors through direct individual endocytosis or in innovative drug delivery systems (DDS) by conjugation with other targeting biomolecules. Purpose: In this mini review, we focus on the use of localized surface plasmon resonance (LSPR)-/surface-enhanced Raman scattering (SERS)- and fluorescence-based diagnosis of NM NMs in the hematological malignancies. Furthermore, the treatment of hematological malignancies utilized the NM NMs or NM NMs-based therapy technology in the chemotherapy, targeted therapy, and photothermal therapy are depicted in depth. The construction of effective and promising NM NMs or NM NMs- dependent theranostic methodology has the potential to provide interdisciplinary knowledge in the development of clinical tracing, diagnosis and treatment of refractory hematological diseases.

Background Endothelial NO synthase plays a central role in regulating vasodilation and blood pressure. Intracellular Ca2+ mobilization is a critical modulator of endothelial NO synthase function, and increased cytosolic Ca2+ concentration in endothelial cells is able to induce endothelial NO synthase phosphorylation. Ca2+ release mediated by 3 subtypes of inositol 1,4,5‐trisphosphate receptors (IP3Rs) from the endoplasmic reticulum and subsequent Ca2+ entry after endoplasmic reticulum Ca2+ store depletion has been proposed to be the major pathway to mobilize Ca2+ in endothelial cells. However, the physiological role of IP3Rs in regulating blood pressure remains largely unclear. Methods and Results To investigate the role of endothelial IP3Rs in blood pressure regulation, we first generated an inducible endothelial cell–specific IP3R1 knockout mouse model and found that deletion of IP3R1 in adult endothelial cells did not affect vasodilation and blood pressure. Considering all 3 subtypes of IP3Rs are expressed in mouse endothelial cells, we further generated inducible endothelial cell–specific IP3R triple knockout mice and found that deletion of all 3 IP3R subtypes decreased plasma NO concentration and increased basal blood pressure. Furthermore, IP3R deficiency reduced acetylcholine‐induced vasodilation and endothelial NO synthase phosphorylation at Ser1177. Conclusions Our results reveal that IP3R‐mediated Ca2+ release in vascular endothelial cells plays an important role in regulating vasodilation and physiological blood pressure.

Inspired by electrically active tissues, conductive materials have been extensively developed for electrically active tissue engineering scaffolds. In addition to excellent conductivity, nanocomposite conductive materials can also provide nanoscale structure similar to the natural extracellular microenvironment. Recently, the combination of three-dimensional (3D) printing and nanotechnology has opened up a new era of conductive tissue engineering scaffolds exhibiting optimized properties and multifunctionality. Furthermore, in the case of two-dimensional (2D) conductive film scaffolds such as periosteum, nerve membrane, skin repair, etc., the traditional preparation process, such as solvent casting, produces 2D films with defects of unequal bubbles and thickness frequently. In this study, poly-l-lactide (PLLA) conductive scaffolds incorporated with polypyrrole (PPy) nanoparticles, which have multiscale structure similar to natural tissue, were prepared by combining extrusion-based low-temperature deposition 3D printing with freeze-drying. Furthermore, we creatively integrated the advantages of 3D printing and solvent casting and successfully developed a 2D conductive film scaffold with no bubbles, uniform thickness, and good structural stability. Subsequently, the effects of concentration and morphology of PPy nanoparticles on electrical properties and mechanical properties of 3D conductive scaffolds and 2D conductive films scaffolds have been studied, which provided a new idea for the design of both 2D and 3D electroactive tissue engineering scaffolds.

The mechanism of biocontrol agent Saccharothrix yanglingensis Hhs.015 action against Valsa mali, a major apple Valsa canker pathogen, was examined using a novel, sensitive (minimum detection limit 100 pg/μL) and reliably RT-qPCR technique. Prior to lesion formation, total concentration of V. mali in the bark showed a significant decrease (p

Targeted therapy for cancer is a research area of great interest, and magnetic nanoparticles (MNPs) show great potential as targeted carriers for therapeutics. One important class of cancer biomarkers is microRNAs (miRNAs), which play a significant role in tumor initiation and progression. In this study, a cascade recognition system containing multiple plasmids, including a Tet activator, a lacI repressor gene driven by the TetOn promoter, and a reporter gene repressed by the lacI repressor and influenced by multiple endogenous miRNAs, was used to recognize cells that display miRNA signals that are characteristic of cancer. For this purpose, three types of signal miRNAs with high proliferation and metastasis abilities were chosen (miR-21, miR-145, and miR-9). The response of this system to the human breast cancer MCF-7 cell line was 3.2-fold higher than that to the human breast epithelial HBL100 cell line and almost 7.5-fold higher than that to human embryonic kidney HEK293T cells. In combination with polyethyleneimine-modified MNPs, this recognition system targeted the tumor location in situ in an animal model, and an ≃42% repression of tumor growth was achieved. Our study provides a new combination of magnetic nanocarrier and gene therapy based on miRNAs that are active in vivo, which has potential for use in future cancer therapies.

An antimicrobial decapeptide, KSL-W (KKVVFWVKFK-CONH2), which could maintain stable antimicrobial activity in saliva, has therefore been widely used to inhibit biofilm formation on teeth and prevent the growth of oral microorganisms for related infectious diseases treatment. In order to control the release of KSL-W for long-term bacterial resistance, KSL-W-loaded PLGA/chitosan composite microspheres (KSL/PLGA/CS MSs) were prepared by electrospraying and combined crosslinking-emulsion methods. Different formulations of microspheres were characterized as to surface morphology, size distribution, encapsulation efficiency, in vitro drug release, and antimicrobial activity. Antibacterial experiment demonstrated the prolonged antimicrobial and inhibitory effects of KSL/PLGA/CS MSs on oral bacteria. Moreover, the cell proliferation assay proved that the released KSL-W antibacterial dosage had no cytotoxicity to the growth of osteoblast MC3T3-E1. Thus, our study suggested that the KSL-W-loaded PLGA/CS composite microspheres may have potentially therapeutic applications as an effective drug delivery system in the treatment of oral infectious diseases such as periodontitis and periodontitis, and also within bone graft substitutes for alveolar bone augmentation.

Spectro-temporal receptive fields (STRFs) have been widely used as linear approximations to the signal transform from sound spectrograms to neural responses along the auditory pathway. Their dependence on statistical attributes of the stimuli, such as sound intensity, is usually explained by nonlinear mechanisms and models. Here, we apply an efficient coding principle which has been successfully used to understand receptive fields in early stages of visual processing, in order to provide a computational understanding of the STRFs. According to this principle, STRFs result from an optimal tradeoff between maximizing the sensory information the brain receives, and minimizing the cost of the neural activities required to represent and transmit this information. Both terms depend on the statistical properties of the sensory inputs and the noise that corrupts them. The STRFs should therefore depend on the input power spectrum and the signal-to-noise ratio, which is assumed to increase with input intensity. We analytically derive the optimal STRFs when signal and noise are approximated as Gaussians. Under the constraint that they should be spectro-temporally local, the STRFs are predicted to adapt from being band-pass to low-pass filters as the input intensity reduces, or the input correlation becomes longer range in sound frequency or time. These predictions qualitatively match physiological observations. Our prediction as to how the STRFs should be determined by the input power spectrum could readily be tested, since this spectrum depends on the stimulus ensemble. The potentials and limitations of the efficient coding principle are discussed.