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Member 5 of the Upper Triassic Xujiahe Formation (T3X5) in central Sichuan Basin has made a breakthrough in exploration recently. However, this new stratum has not been investigated sufficiently with respect to basic geology, making its types and distribution of sedimentary facies unclear, which severely restricts its subsequent exploration evaluation. In this study, types of sedimentary microfacies in the first sand group of T3X5 (T3X51) are clarified through core observation and logging interpretation using core, log and seismic data, and then distribution of sedimentary microfacies in T3X51 is determined according to seismic waveform features and seismic prediction. The results show that T3X51 in the Dongfengchang area is mainly composed of deltaic deposits of several microfacies, such as delta front underwater distributary channel, sheet sand, and interdistributary bay. On seismic sections, different microfacies are significantly different in waveform features, the underwater distributary channel is characterized by one trough between two peaks, while diversion bay exhibits chaotic reflections between T6 and T51. The sedimentary microfacies varied greatly during the depositional period of T3X51 in the Dongfengchang area, this is because that the sediment supply was mainly controlled by the southwest and southeast provenance regions. Three superimposed underwater distributary channels are developed in the Dongfengchang area. The phase-1 superimposed underwater distributary channel in the northwest transition to sheet sand in the northeast, the phase-2 superimposed underwater distributary channel in the south extends shortly, the phase-3 superimposed underwater distributary channel in the northeast has a large development scale. These research findings are helpful to guide the subsequent exploration of T3X5 gas reservoir and also theoretically significant for investigating the depositional evolution of the Xujiahe Formation in central Sichuan Basin.

The incorporation of commercial flame retardants into fiber-reinforced polymer (FRP) composites has been proposed as a potential solution to improve the latter’s poor flame resistance. However, this approach often poses a challenge, as it can adversely affect the mechanical properties of the FRP. Thus, balancing the need for improved flame resistance with the preservation of mechanical integrity remains a complex issue in FRP research. Addressing this critical concern, this study introduces a novel additive system featuring a combination of one-dimensional (1D) hollow tubular structured halloysite nanotubes (HNTs) and two-dimensional (2D) polygonal flake-shaped nano kaolinite (NKN). By employing a 1D/2D hybrid kaolinite nanoclay system, this research aims to simultaneously improve the flame retardancy and mechanical properties. This innovative approach offers several advantages. During combustion and pyrolysis processes, the 1D/2D hybrid kaolinite nanoclay system proves effective in reducing heat release and volatile leaching. Furthermore, the system facilitates the formation of reinforcing skeletons through a crosslinking mechanism during pyrolysis, resulting in the development of a compact char layer. This char layer acts as a protective barrier, enhancing the material’s resistance to heat and flames. In terms of mechanical properties, the multilayered polygonal flake-shaped 2D NKN plays a crucial role by impeding the formation of cracks that typically arise from vulnerable areas, such as adhesive phase particles. Simultaneously, the 1D HNT bridges these cracks within the matrix, ensuring the structural integrity of the composite material. In an optimal scenario, the homogeneously distributed 1D/2D hybrid kaolinite nanoclays exhibit remarkable results, with a 51.0% improvement in mode II fracture toughness (GIIC), indicating increased resistance to crack propagation. In addition, there is a 34.5% reduction in total heat release, signifying improved flame retardancy. This study represents a significant step forward in the field of composite materials. The innovative use of hybrid low-dimensional nanomaterials offers a promising avenue for the development of multifunctional composites. By carefully designing and incorporating these nanoclays, researchers can potentially create a new generation of FRP composites that excel in both flame resistance and mechanical strength.

Abstract Objective The persistent symptoms arising from COVID-19 infection pose a substantial threat to patients’ health, carrying significant implications. Amidst the evolving COVID-19 control strategies in China, healthcare workers (HCWs) endure considerable stress. This study aims to evaluate the prevalence of long COVID infections and their influencing factors among primary HCWs after epidemic control policy adjustment in Jiangsu. Methods A self-designed questionnaire was administered through on-site surveys among primary HCWs in five counties and districts within Jiangsu Province from July 4 to July 20, 2023. Logistic regression analysis was employed to identify factors associated with long COVID. Results The prevalence of long COVID among primary HCWs stood at 12.61%, with a 95% confidence interval (CI) of 11.67-13.55%. Among those affected, the most common long COVID symptoms were hypomnesia (4.90%, 95%CI: 4.29-5.51%), sleep difficulties (2.73%, 95%CI: 2.27-3.19%), fatigue (2.35%, 95%CI: 1.92-2.78%), disturbances in the reproductive system (1.93%, 95%CI: 1.54-2.32%), hair loss (1.85%, 95%CI: 1.47-2.23%), and myalgia/arthralgia (1.51%, 95%CI: 1.16-1.86%). Multivariate logistic regression revealed that older age groups (30–45 years (adjusted odds ratio (aOR) = 1.93, 95%CI: 1.44–2.58), 45–60 years (aOR = 2.82, 95%CI: 2.07–3.84)), females (aOR = 1.26, 95%CI: 1.03–1.55), and higher work stress (high stress (aOR = 1.52, 95%CI: 1.24–1.86), extremely high stress (aOR = 1.37, 95%CI: 1.03–1.82)) were more prone to long COVID. Conversely, individuals with educational attainment below the bachelor’s degree (aOR = 0.67, 95%CI: 0.55–0.82) and those who received four or more doses of the COVID-19 vaccine (aOR = 0.55, 95%CI: 0.33–0.92) were at a reduced risk. Conclusion This study investigates the prevalence of long COVID among primary HCWs and identifies key influencing factors. These findings are crucial for assisting in the early identification of COVID-19 patients at risk for long-term complications, developing targeted interventions aimed at optimizing healthcare resource allocation and enhancing the work conditions and quality of life of HCWs. To mitigate the prevalence of long COVID, healthcare providers and local authorities should implement effective measures, such as optimizing work-rest schedules and actively advocating for vaccination.

ObjectiveTo investigate potential causative associations between immunophenotype traits and cervical cancer by using two-sample Mendelian randomization (MR) analysis. MethodsThe genetic instrumental variables (IVs) of 731 immunophenotypes of peripheral blood were obtained from the GWAS Catalog database. The GWAS summary data of cervical cancer were obtained from FinnGen database. The inverse-variance weighted (IVW), weighted mode, weighted median, and MR Egger methods were used for evaluations. The sensitivity analysis and reverse Mendelian randomization analysis were conducted to eliminate bias and reverse causality. The MR Steiger directionality test was further used to ascertain the reverse causal relationship between immune cells and cervical cancer. ResultsA total of 71 immune cell subtypes associated with cervical cancer were identified, of which 31 had a strong association. The majority of the B cell panel was protective factors for cervical cancer. B-cell activating factor receptor (BAFF-R) was the most frequently expressed molecule in this analysis. It is expressed on several B cell subtypes. The CD20 on IgD+ CD38+ B cell (OR=1.887, 95%CI: 1.078-3.306, P=0.026) is the risk factor for cervical cancer. In cDC panels, the CD123 expression on plasmacytoid dendritic cell (OR=2.48, 95%CI: 1.229-5.003, P=0.011), CD123 expression on CD62L+ plasmacytoid dendritic cell (OR=2.5, 95%CI: 1.231-5.077, P=0.011), CD80 expression on plasmacytoid dendritic cell (OR=2.62,95%CI:1.244-5.515, P=0.011), and CD80 expression on CD62L+ plasmacytoid dendritic cell (OR=2.641, 95%CI: 1.246-5.596, P=0.011) were positively associated with the incidence of cervical cancer. All gynecological cancers in this study have no statistically significant effect on immune cells, according to reverse MR analysis. ConclusionThis study emphasized the genetically predicted causality between immune cells and cervical cancer. In clinical practice, it is important to pay attention to the screening of peripheral blood immune cells for patients with cervical cancer.

Abstract Background Thoracoscopic-guided thoracic paravertebral nerve block (TG-TPVB) and thoracoscopic-guided intercostal nerve block (TG-INB) are two postoperative analgesia technology for thoracic surgery. This study aims to compared the analgesic effect of TG-TPVB and TG-INB after uniportal video-asssited thoracic surgery (UniVATS). Methods Fifty-eight patients were randomly allocated to the TG-TPVB group and the TG-INB group. The surgical time of nerve block, the visual analog scale (VAS) scores, the consumption of sufentanil and the number of patient-controlled intravenous analgesic (PCIA) presses within 24 h after surgery, the incidence of adverse reactions were compared between the two groups. Results The VAS scores were significantly lower during rest and coughing at 2, 6, 12, and 24 h in the TG-TPVB group than in the TG-INB group (P

Abstract Heat stress (HS) poses a significant challenge to plant survival, necessitating sophisticated molecular mechanisms to maintain cellular homeostasis. Here, we identify SICKLE (SIC) as a key modulator of HS responses in Arabidopsis (Arabidopsis thaliana). SIC is required for the sequestration of RNA DEBRANCHING ENZYME 1 (DBR1), a rate-limiting enzyme of lariat intronic RNA (lariRNA) decay, into stress granules (SGs). The sequestration of DBR1 by SIC enhances the accumulation of lariRNAs, branched circular RNAs derived from excised introns during pre-mRNA splicing, which in turn promote the transcription of their parental genes. Our findings further demonstrate that SIC-mediated DBR1 sequestration in SGs is crucial for plant HS tolerance, as deletion of the N-terminus of SIC (SIC1–244) impairs DBR1 sequestration and compromises plant response to HS. Overall, our study unveils a mechanism of transcriptional regulation in the HS response, where lariRNAs are enriched through DBR1 sequestration, ultimately promoting the transcription of heat stress tolerance genes.

Abstract The Ideal Plant Architecture 1 (IPA1) transcription factor promotes rice yield and immunity through phosphorylation at its amino acid residue Ser163 as a switch. Although phosphorylated IPA1 mimic, IPA1(S163D), directly targets the promoter of immune response gene WRKY45, it cannot activate its expression. Here, we identified a co-activator of IPA1(S163D), a RING-finger E3 ligase IPA1 interactor 7 (IPI7), which fine-tunes the transcriptional activity of IPA1 to timely promote plant immunity and simultaneously maintain growth for yield. IPI7 interacts with IPA1 and promotes K29-polyubiquitination of IPA1 in vitro and in vivo. However, the stability of IPA1 protein is not affected by IPI7-mediated ubiquitination. The IPI7-promoted K29-polyubiquitination of IPA1 is induced by Magnaporthe oryzae infection and required for phosphorylated IPA1 to transactivate WRKY45 expression for immune response but not for plain IPA1 to transactivate DENSE AND ERECT PANICLES 1 (DEP1) expression for panicle development. IPI7 knockout impairs IPA1-mediated immunity but not yield. Our study reveals that plants utilize non-proteolytic K29-ubiquitination as a response to pathogen infection to fine-tune IPA1 transactivation activity for promoting immunity.

Abstract Acute kidney injury (AKI) is a clinical condition characterized by a rapid decline in kidney function, which is associated with local inflammation and programmed cell death in the kidney. The G protein-coupled receptors (GPCRs) represent the largest family of signaling transduction proteins in the body, and approximately 40% of drugs on the market target GPCRs. The expressions of various GPCRs, prostaglandin receptors and purinergic receptors, to name a few, are significantly altered in AKI models. And the role of GPCRs in AKI is catching the eyes of researchers due to their distinctive biological functions, such as regulation of hemodynamics, metabolic reprogramming, and inflammation. Therefore, in this review, we aim to discuss the role of GPCRs in the pathogenesis of AKI and summarize the relevant clinical trials involving GPCRs to assess the potential of GPCRs and their ligands as therapeutic targets in AKI and the transition to AKI-CKD.

Abstract Metalenses can integrate the functionalities of multiple optical components thanks to the unprecedented capability of optical metasurfaces in light control. With the rapid development of optical metasurfaces, metalenses continue to evolve. Polarization and color play a very important role in understanding optics and serve as valuable tools for gaining insights into our world. Benefiting from the design flexibility of metasurfaces, we propose and experimentally demonstrate a super metalens that can realize multifaceted control of focal points along any 3D curved trajectory. The wavelengths and polarization states of all focal points are engineered in a desirable manner. The super metalens can simultaneously realize customized 3D positioning, polarization states, and wavelengths of focal points, which are experimentally demonstrated with incident wavelengths ranging from 501 to 700 nm. We further showcase the application of the developed super metalenses in 3D optical distance measurement. The compact nature of metasurfaces and unique properties of the proposed super metalenses hold promise to dramatically miniaturize and simplify the optical architecture for applications in optical metrology, imaging, detection, and security.

The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

The intracellular lipids in muscle cells of farm animals play a crucial role in determining the overall intramuscular fat (IMF) content, which has a positive impact on meat quality. However, the mechanisms underlying the deposition of lipids in muscle cells of farm animals are not yet fully understood. The purpose of this study was to determine the roles of carbohydrate-response element binding protein (ChREBP) and fructose in IMF deposition of chickens. For virus-mediated ChREBP overexpression in tibialis anterior (TA) muscle of chickens, seven 5-d-old male yellow-feather chickens were used. At 10 d after virus injection, the chickens were slaughtered to obtain TA muscles for analysis. For fructose administration trial, sixty 9-wk-old male yellow-feather chickens were randomly divided into 2 groups, with 6 replicates per group and 5 chickens per replicate. The chickens were fed either a basal diet or a basal diet supplemented with 10% fructose (purity ≥ 99%). At 4 wk later, the chickens were slaughtered, and breast and thigh muscles were collected for analysis. The results showed that the skeletal ChREBP mRNA levels were positively associated with IMF content in multiple species, including the chickens, pigs, and mice (P

In multi-ethnic rural settlements, a diversity of social relationships gives rise to various public spaces. The integration of cultures, propelled by urbanization, poses challenges to the unique characteristics of these rural public spaces. This process leads to issues such as the loss of cultural diversity, increased homogeneity of spaces, uneven distribution of public services, and low efficiency in space utilization, which seriously interfere with the healthy and sustainable development of rural social systems in multi-ethnic rural areas. This study, focusing on the rural public spaces in Tongren's multi-ethnic settlements, employs a social network analysis approach to investigate the implications of these spaces for the stability of rural community life and the preservation of cultural identities. A model for analyzing social networks in rural public spaces was developed, emphasizing overlapping patterns of user groups, activities, and spatial entities. Analysis of the social networks was conducted in three domains: emotional support, material exchange, and information dissemination. A semantic model was also constructed to understand the usage and structural networks within these public spaces. Comparative analyses between the usage and structural networks of rural public spaces were conducted to develop a comprehensive structural analysis system for these areas. Application of this system in analyzing the rural public spaces of Tongren revealed distinct findings. The connectivity of the structural network in Dongganmu Village's public spaces was found to be lower than that of the usage network, indicating that social factors heavily influence villagers' interactions. Furthermore, the number of small groups within the usage network was fewer than in the structural network, reflecting a lack of hierarchy in public space organization. Villagers’ preferences for public spaces were primarily influenced by cultural beliefs rather than spatial accessibility. The insights garnered from this study not only contribute to the understanding of social network structures in rural public spaces within multi-ethnic settlements but also provide a foundation for informed decision-making regarding the sustainable development of these areas.

Abstract Acute lung injury (ALI) is a severe clinical respiratory condition characterized by high rates of mortality and morbidity, for which effective treatments are currently lacking. In this study, lipopolysaccharide (LPS) was used to induce ALI mice, demonstrating the efficacy of tetramethylpyrazine (TMP) in ameliorating ALI. Subsequent we perfored high-throughput sequencing analysis and used Targetscan 8.0 and miRWalk 3.0 databases to predict the interaction between microRNAs and destrin (DSTN), ultimately identifying miR-369-3p as the focus of the investigation. The adenovirus carrying miR-369-3p was administered one week prior to LPS-induced in order to assess its potential efficacy in ameliorating ALI in mice. The findings indicated that the overexpression of miR-369-3p resulted in enhanced lung function, reduced pulmonary edema, inflammation, and permeability in LPS-induced ALI mice, while the suppression of miR-369-3p exacerbated the damage in these mice. Furthermore, the beneficial effects of TMP on LPS-induced ALI were negated by the downregulation of miR-369-3p. The results of our study demonstrate that TMP mitigates LPS-induced ALI through upregulation of miR-369-3p. Consequently, the findings of this study advocate for the clinical utilization of TMP in ALI treatment, with miR-369-3p emerging as a promising target for future ALI interventions.

Abstract Background Cabbage Fusarium wilt (CFW) is a devastating disease caused by the soil-borne fungus Fusarium oxysporum f. sp. conglutinans (Foc). One of the optimal measures for managing CFW is the employment of tolerant/resistant cabbage varieties. However, the interplay between plant genotypes and the pathogen Foc in shaping the rhizosphere microbial community, and the consequent influence of these microbial assemblages on biological resistance, remains inadequately understood. Results Based on amplicon metabarcoding data, we observed distinct differences in the fungal alpha diversity index (Shannon index) and beta diversity index (unweighted Bray–Curtis dissimilarity) within the rhizosphere of the YR (resistant to Foc) and ZG (susceptible to Foc) cabbage varieties, irrespective of Foc inoculation. Notably, the Shannon diversity shifts in the resistant YR variety were more pronounced following Foc inoculation. Disease-resistant plant variety demonstrate a higher propensity for harboring beneficial microorganisms, such as Pseudomonas, and exhibit superior capabilities in evading harmful microorganisms, in contrast to their disease-susceptible counterparts. Furthermore, the network analysis was performed on rhizosphere-associated microorganisms, including both bacteria and fungi. The networks of association recovered from YR exhibited greater complexity, robustness, and density, regardless of Foc inoculation. Following Foc infection in the YR rhizosphere, there was a notable increase in the dominant bacterium NA13, which is also a hub taxon in the microbial network. Reintroducing NA13 into the soil significantly improved disease resistance in the susceptible ZG variety, by directly inhibiting Foc and triggering defense mechanisms in the roots. Conclusions The rhizosphere microbial communities of these two cabbage varieties are markedly distinct, with the introduction of the pathogen eliciting significant alterations in their microbial networks which is correlated with susceptibility or resistance to soil-borne pathogens. Furthermore, we identified a rhizobacteria species that significantly boosts disease resistance in susceptible cabbages. Our results indicated that the induction of resistance genes leading to varied responses in microbial communities to pathogens may partly explain the differing susceptibilities of the cabbage varieties tested to CFW. Video Abstract

Abstract Background Insulin resistance (IR) is related with adverse outcomes of in vitro fertilization (IVF) in women with obesity, but little is known about the relationship between IR and unexpected poor ovarian response (uPOR) in non-obese subjects with sufficient ovarian parameters (classified as POSEIDON group 1). This research aims to explore the association between the homeostasis model assessment of insulin resistance (HOMA-IR) and uPOR in non-obese women with normal biomarkers of ovarian reserve. Methods The retrospective cohort study was conducted at a fertility center. The main inclusion criteria were age

Abstract Background Cardiac iron overload and ferroptosis greatly contribute to the poor prognosis of myocardial infarction (MI). Iron chelator is one of the most promising strategies for scavenging excessive iron and alleviating cardiac dysfunction post MI. However, various side effects of existing chemical iron chelators restrict their clinical application, which calls for a more viable and safer approach to protect against iron injury in ischemic hearts. Results In this study, we isolated macrophage-derived extracellular vesicles (EVs) and identified macrophage-derived EVs as a novel endogenous biological chelator for iron. The administration of macrophage-derived EVs effectively reduced iron overload in hypoxia-treated cardiomyocytes and hearts post MI. Moreover, the oxidative stress and ferroptosis induced by excessive iron were considerably suppressed by application of macrophage-derived EVs. Mechanistically, transferrin receptor (TfR), which was inherited from macrophage to the surface of EVs, endowed EVs with the ability to bind to transferrin and remove excess protein-bound iron. EVs with TfR deficiency exhibited a loss of function in preventing MI-induced iron overload and protecting the heart from MI injury. Furthermore, the iron-chelating EVs were ultimately captured and processed by macrophages in the liver. Conclusions These results highlight the potential of macrophage-derived EVs as a powerful endogenous candidate for iron chelation therapy, offering a novel and promising therapeutic approach to protect against iron overload-induced injury in MI and other cardiovascular diseases.

A dehydroxylative ring-opening Giese reaction of cyclobutanone oximes enabled by photoredox/Ti dual catalysis has been reported in this work. This protocol avoids the prefunctionalization of oximes and the use of stoichiometric triarylphosphine reagents. It also features mild conditions, broad substrate scope and good functional group tolerance. The gram-scale reaction, product derivatization, late-stage functionalization of complex pharmaceutical and natural product derivatives, and oligopeptide modification exhibit the potential application of this methodology in synthetic chemistry.

The Sichuan Basin, located in southwestern China, is considered the primary producing area for shale gas development in the country. Its rich shale gas reserves have made it a significant contributor to China’s energy production. Within the Sichuan Basin, northeast Sichuan has emerged as a region of particular interest for shale gas development. In order to investigate the controlling factors and enrichment patterns of organic matter-rich shales from the Upper Ordovician Wufeng Formation-Lower Silurian Longmaxi Formation in northeast Sichuan, inductively coupled plasma mass spectrometry (ICP–MS) was used to analyze 14 shale samples from the Wufeng Formation-Longmaxi Formation in northeast Sichuan. Combined with the characteristics of logging curves, the sedimentary system, redox conditions, terrestrial debris input, primary productivity, and paleoclimate relationship of the Wufeng Formation to the Longmaxi Formation were explored. As a result, three third-order sequences (SSQ1, SSQ2, and SSQ3) were identified, and the sea level experienced a process from high-low-high-low, which, in combination with the shale elemental parameters of w(V)/w(Cr), w(V)/w(V+Ni), w(Ni)/w(Co), w(Sr)/w(Cu), w(Sr)/w(Ba), and T (℃), indicated that the Wufeng Formation-Longmaxi Formation underwent an oxidized-poorly oxygenated-anoxic reduced-poorly oxygenated-oxidized freshwater environment; the climate has undergone a warm-humid, dry-cold, warm-humid, dry-cold, warm-humid evolution, and the temperature has gone through the process of decreasing – increasing – decreasing – increasing. The organic matter enrichment pattern of the Wufeng Formation-Longmaxi Formation in northeast Sichuan can be divided into a Ⅲ stage pattern. Stage Ⅰ, the depositional period from the Wufeng Formation to the bottom of the Longmaxi Formation, is a stage of gradual increase in organic carbon; stage Ⅱ, the depositional period of the middle part of the Longmaxi Formation, is a stage of enrichment of organic carbon (sweet-spot member); and stage Ⅲ, the depositional period of the upper part of the Longmaxi Formation, is a stage of gradual decrease in organic carbon. It is expected to provide a basis for the exploration of shale gas in northeast Sichuan, and the next step will be to carry out research on the resource response of major geological events to organic matter enrichment in the study area and deepen the shale gas enrichment model.

Abstract Transcription, RNA splicing, RNA translation, and post-translational protein modification are fundamental processes of gene expression. Epigenetic modifications, such as DNA methylation, RNA modifications, and protein modifications, play a crucial role in regulating gene expression. The methyltransferase-like protein (METTL) family, a constituent of the 7-β-strand (7BS) methyltransferase subfamily, is broadly distributed across the cell nucleus, cytoplasm, and mitochondria. Members of the METTL family, through their S-adenosyl methionine (SAM) binding domain, can transfer methyl groups to DNA, RNA, or proteins, thereby impacting processes such as DNA replication, transcription, and mRNA translation, to participate in the maintenance of normal function or promote disease development. This review primarily examines the involvement of the METTL family in normal cell differentiation, the maintenance of mitochondrial function, and its association with tumor formation, the nervous system, and cardiovascular diseases. Notably, the METTL family is intricately linked to cellular translation, particularly in its regulation of translation factors. Members represent important molecules in disease development processes and are associated with patient immunity and tolerance to radiotherapy and chemotherapy. Moreover, future research directions could include the development of drugs or antibodies targeting its structural domains, and utilizing nanomaterials to carry miRNA corresponding to METTL family mRNA. Additionally, the precise mechanisms underlying the interactions between the METTL family and cellular translation factors remain to be clarified.

Abstract The investigation of hadron interactions within lattice QCD has been facilitated by the well-known quantisation condition, linking scattering phase shifts to finite-volume energies. Additionally, the ability to utilise systems at finite total boosts has been pivotal in smoothly charting the energy-dependent behaviour of these phase shifts. The existing implementations of the quantization condition at finite boosts rely on momentum transformations between rest and moving frames, defined directly in terms of the energy eigenvalues. This energy dependence is unsuitable in the formulation of a Hamiltonian. In this work, we introduce a novel approach to generalise the three-momentum boost prescription, enabling the incorporation of energy-independent finite-volume Hamiltonians within moving frames. We demonstrate the application of our method through numerical comparisons, employing a phenomenological ππ scattering example.

The content of stannous chloride is one of the key indicators for the quality control of Technetium [99mTc] radiopharmaceutical injection Kits，which directly affects the clinical use of Technetium [99mTc] radiopharmaceuticals. Consequently，it is crucial to choose the appropriate analytical method for its accurate determination. By comparing the quality standards of radiopharmaceuticals included in the 2020 edition of the Chinese Pharmacopoeia and other related literature，the characteristics，determination principles and applications of commonly used methods for the determination of stannous chloride，including potentiometric analysis，spectrophotometry and high-performance liquid chromatography，were analyzed and summarized. This work provided technical reference for the establishment of a more scientific and rational quality standard for Technetium [99mTc] radiopharmaceutical injection kits.

Abstract In the detection of multi‐component gas based on tunable diode laser absorption spectroscopy (TDLAS), the problem of overlapping interference between the absorption lines of each gas is often encountered. For example, when detecting a gas mixture of sulphur dioxide (SO2) and thionyl fluoride (SOF2), the characteristic decomposition components of SF6, there is overlapping interference in the absorption lines of the two gases, which makes it difficult to detect the concentration of gases accurately. In view of this problem, a novel method based on support vector regression model used for TDLAS is proposed to detect two gases simultaneously. The detection results show that the correlation coefficients between the concentration of SO2 and SOF2 and the average value of the second harmonic peak reached 0.992 and 0.993. In addition, through model testing, different concentrations of SO2 and SOF2 gas mixture are simultaneously detected, and the resulting maximum errors for measuring SO2 and SOF2 concentrations are less than 7.13 × 10−5 and 0.26 × 10−2. The maximum errors of the measurement results in the verification test are not more than 6.4 × 10−3 and 4.6 × 10−2. Therefore, with assistance of the novel method, the detection of multiple gases by using a single laser is achieved.

Abstract Third-generation EGFR tyrosine kinase inhibitors (TKIs), exemplified by osimertinib, have demonstrated promising clinical efficacy in the treatment of non-small cell lung cancer (NSCLC). Our previous work has identified ASK120067 as a novel third-generation EGFR TKI with remarkable antitumor effects that has undergone New Drug Application (NDA) submission in China. Despite substantial progress, acquired resistance to EGFR-TKIs remains a significant challenge, impeding the long-term effectiveness of therapeutic approaches. In this study, we conducted a comprehensive investigation utilizing high-throughput proteomics analysis on established TKI-resistant tumor models, and found a notable upregulation of branched-chain amino acid transaminase 1 (BCAT1) expression in both osimertinib- and ASK120067-resistant tumors compared with the parental TKI-sensitive NSCLC tumors. Genetic depletion or pharmacological inhibition of BCAT1 impaired the growth of resistant cells and partially re-sensitized tumor cells to EGFR TKIs. Mechanistically, upregulated BCAT1 in resistant cells reprogrammed branched-chain amino acid (BCAA) metabolism and promoted alpha ketoglutarate (α-KG)-dependent demethylation of lysine 27 on histone H3 (H3K27) and subsequent transcriptional derepression of glycolysis-related genes, thereby enhancing glycolysis and promoting tumor progression. Moreover, we identified WQQ-345 as a novel BCAT1 inhibitor exhibiting antitumor activity both in vitro and in vivo against TKI-resistant lung cancer with high BCAT1 expression. In summary, our study highlighted the crucial role of BCAT1 in mediating resistance to third-generation EGFR-TKIs through epigenetic activation of glycolysis in NSCLC, thereby supporting BCAT1 as a promising therapeutic target for the treatment of TKI-resistant NSCLC.

Abstract Background Influenza, an acute infectious respiratory disease, presents a significant global health challenge. Accurate prediction of influenza activity is crucial for reducing its impact. Therefore, this study seeks to develop a hybrid Convolution Neural Network—Long Short Term Memory neural network (CNN-LSTM) model to forecast the percentage of influenza-like-illness (ILI) rate in Hebei Province, China. The aim is to provide more precise guidance for influenza prevention and control measures. Methods Using ILI% data from 28 national sentinel hospitals in the Hebei Province, spanning from 2010 to 2022, we employed the Python deep learning framework PyTorch to develop the CNN-LSTM model. Additionally, we utilized R and Python to develop four other models commonly used for predicting infectious diseases. After constructing the models, we employed these models to make retrospective predictions, and compared each model’s prediction performance using mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE), and other evaluation metrics. Results Based on historical ILI% data from 28 national sentinel hospitals in Hebei Province, the Seasonal Auto-Regressive Indagate Moving Average (SARIMA), Extreme Gradient Boosting (XGBoost), Convolution Neural Network (CNN), Long Short Term Memory neural network (LSTM) models were constructed. On the testing set, all models effectively predicted the ILI% trends. Subsequently, these models were used to forecast over different time spans. Across various forecasting periods, the CNN-LSTM model demonstrated the best predictive performance, followed by the XGBoost model, LSTM model, CNN model, and SARIMA model, which exhibited the least favorable performance. Conclusion The hybrid CNN-LSTM model had better prediction performances than the SARIMA model, CNN model, LSTM model, and XGBoost model. This hybrid model could provide more accurate influenza activity projections in the Hebei Province.

Abstract Background The objective of this study is to illustrate the changes in the choroidal vasculature in individuals with diffuse chorioretinal atrophy (DCA, early-stage myopic maculopathy) and investigate the association between them. Methods This study included 1418 highly myopic eyes from 720 participants aged 18 − 60 years from the Wenzhou High Myopia Cohort Study. These participants underwent comprehensive ophthalmic assessments. Myopic maculopathy classification followed the Meta-PM system, with pathological myopia defined as myopic maculopathy of DCA or severer. Eyes with myopic maculopathy categorized as no macular lesions (C0), tessellated fundus (C1), and DCA (C2) were enrolled in the analysis. Choroidal images were obtained from swept-source optical coherence tomography (SS-OCT), and the images were processed with a deep learning-based automatic segmentation algorithm and the Niblack auto-local threshold algorithm. Results DCA was detected in 247 eyes (17.4%). In comparison to eyes with C0, those with C2 exhibited significant reductions in choroidal thickness (ChT), luminal area (LA), and stromal area (SA) across all evaluated regions (all P

Abstract TFE3 and TFEB, as the master regulators of lysosome biogenesis and autophagy, are well characterized to enhance the synaptic protein α-synuclein degradation in protecting against Parkinson’s disease (PD) and their levels are significantly decreased in the brain of PD patients. However, how TFE3 and TFEB are regulated during PD pathogenesis remains largely vague. Herein, we identified that programmed cell death 4 (PDCD4) promoted pathologic α-synuclein accumulation to facilitate PD development via suppressing both TFE3 and TFEB translation. Conversely, PDCD4 deficiency significantly augmented global and nuclear TFE3 and TFEB distributions to alleviate neurodegeneration in a mouse model of PD with overexpressing α-synuclein in the striatum. Mechanistically, like TFEB as we reported before, PDCD4 also suppressed TFE3 translation, rather than influencing its transcription and protein stability, to restrain its nuclear translocation and lysosomal functions, eventually leading to α-synuclein aggregation. We proved that the two MA3 domains of PDCD4 mediated the translational suppression of TFE3 through binding to its 5’-UTR of mRNA in an eIF-4A dependent manner. Based on this, we developed a blood-brain barrier penetrating RVG polypeptide modified small RNA drug against pdcd4 to efficiently prevent α-synuclein neurodegeneration in improving PD symptoms by intraperitoneal injections. Together, we suggest PDCD4 as a PD-risk protein to facilitate α-synuclein neurodegeneration via suppressing TFE3 and TFEB translation and further provide a potential small RNA drug against pdcd4 to treat PD by intraperitoneal injections.

Abstract Single B-cell antibody generation technology is an advanced method that offers several advantages, including rapid production, high efficiency, and high yield. The antibodies generated via this technique retain their natural conformation and are well suited for applications in pathogen diagnosis, disease treatment, and investigations of virus cross-species transmission mechanisms. Our study aimed to establish a platform for generating single B-cell antibodies specifically targeting the foot-and-mouth disease virus (FMDV) 146S antigen in mice. Female BALB/c mice were immunized with inactivated O-type FMDV 146S antigen, and spleen cells were collected for further analysis. Flow cytometric sorting was performed using a biotin-labeled O-type FMDV 146S antigen as a decoy to identify and select CD19 + /CD21/35 + /CD43-/IgM-/Biotin + antigen-specific individual B cells. The gene sequences encoding the variable regions of the heavy and light chains of the murine IgG antibodies were obtained via single-cell nested PCR amplification. Separate constructs were created for the heavy and light chain plasmids to ensure the proper expression of intact IgG antibodies. These plasmids were cotransfected into human embryonic kidney 293T (HEK293T) cells, leading to the successful production and purification of 15 specific monoclonal antibodies (mAbs), 10 which exhibited activity in ELISA tests, and six antibodies that displayed activity in IFA tests. These findings highlight the successful development of a method for generating mouse-derived single B-cell antibodies that target FMDV. This achievement provides a solid foundation for diagnostic techniques and the analysis of antigenic structural variations.

Abstract Background Calcification is common in advanced atheromatous plaque, but its clinical significance remains unclear. This study aimed to assess the prevalence of plaque calcification in the moderate-to-severe internal carotid artery stenosis and investigate its relationship with ipsilateral ischemia. Methods The retrospective study included 178 patients detected with proximal internal carotid artery (pICA) stenosis of ≥ 50% on multidetector computed tomography at Zhejiang Hospital from January 2019 to March 2023. Association between plaque calcification characteristics (calcification thickness, position, type, circumferential extent, calcium volume and calcium score) and ipsilateral cerebrovascular events was analyzed. Results The 178 patients (mean age 71.24 ± 10.02 years, 79.78% males) had 224 stenosed pICAs overall. Plaque calcification was noted in 200/224 (89.29%) arteries. Calcification rates were higher in older age-groups. Calcification volume (r = 0.219, p

Abstract Background Despite hip function typically deteriorating in the post-collapse stage of osteonecrosis of the femoral head (ONFH), some patients can still demonstrate long-term favorable hip function, a state termed “survival with collapse”. This study aims to identify the characteristics of patients suitable for “survival with collapse” in cases of ONFH. Methods This cross-sectional study included 65 patients (87 hips) diagnosed with post-collapse ONFH for ≥ 3 years (average 9.1 years, range 3–23 years). Hip function was assessed using the Harris Hip Score (HHS). Demographic, clinical, and radiographic data were compared between the favorable group (HHS > 80) and the poor group (HHS ≤ 80). Independent protective factors for hip function were identified by multivariate analysis and receiver operating characteristic (ROC) curve analysis was further applied to evaluate these factors’ diagnostic efficacy. Results The favorable and poor groups included 46 and 41 hips, respectively. Significant differences were found in body mass index (BMI), Association Research Circulation Osseous (ARCO) stage, collapse degree, Japanese Investigation Committee (JIC) classification, necrotic size, and hip subluxation between the two groups (p

Abstract Despite advances in therapies, glioblastoma (GBM) recurrence is almost inevitable due to the aggressive growth behavior of GBM cells and drug resistance. Temozolomide (TMZ) is the preferred drug for GBM chemotherapy, however, development of TMZ resistance is over 50% cases in GBM patients. To investigate the mechanism of TMZ resistance and invasive characteristics of GBM, analysis of combined RNA-seq and ChIP-seq was performed in GBM cells in response to TMZ treatment. We found that the PERK/eIF2α/ATF4 signaling was significantly upregulated in the GBM cells with TMZ treatment, while blockage of ATF4 effectively inhibited cell migration and invasion. SPHK1 expression was transcriptionally upregulated by ATF4 in GBM cells in response to TMZ treatment. Blockage of ATF4-SPHK1 signaling attenuated the cellular and molecular events in terms of invasive characteristics and TMZ resistance. In conclusion, GBM cells acquired chemoresistance in response to TMZ treatment via constant ER stress. ATF4 transcriptionally upregulated SPHK1 expression to promote GBM cell aggression and TMZ resistance. The ATF4-SPHK1 signaling in the regulation of the transcription factors of EMT-related genes could be the underlying mechanism contributing to the invasion ability of GBM cells and TMZ resistance. ATF4-SPHK1-targeted therapy could be a potential strategy against TMZ resistance in GBM patients.

Spinal cord injury (SCI) is a traumatic condition that results in impaired motor and sensory function. Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord, and ferroptosis inhibitors are effective in reducing inflammation and repairing SCI. Although human umbilical cord mesenchymal stem cells (Huc-MSCs) can ameliorate inflammatory microenvironments and promote neural regeneration in SCI, their efficacy is greatly limited by the local microenvironment after SCI. Therefore, in this study, we constructed a drug-release nanoparticle system with synergistic Huc-MSCs and ferroptosis inhibitor, in which we anchored Huc-MSCs by a Tz-A6 peptide based on the CD44-targeting sequence, and combined with the reactive oxygen species (ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at the other end for SCI repair. Meanwhile, we also modified the classic ferroptosis inhibitor Ferrostatin-1 (Fer-1) and synthesized a new prodrug Feborastatin-1 (Feb-1). The results showed that this treatment regimen significantly inhibited the ferroptosis and inflammatory response after SCI, and promoted the recovery of neurological function in rats with SCI. This study developed a combination therapy for the treatment of SCI and also provides a new strategy for the construction of a drug-coordinated cell therapy system.

The completely autotrophic nitrogen removal over nitrite (CANON) process is significantly hindered by prolonged start-up periods and unstable nitrogen removal efficiency. In this study, a novel umbrella basalt fiber (BF) carrier with good biological affinity and adsorption performance was used to initiate the CANON process. The CANON process was initiated on day 64 in a sequencing batch reactor equipped with umbrella BF carriers. During this period, the influent NH4+-N concentration gradually increased from 100 to 200 mg·L−1, and the dissolved oxygen was controlled below 0.8 mg L−1. Consequently, an average ammonia nitrogen removal efficiency (ARE) and total nitrogen removal efficiency (TNRE) of ∼90 and 80% were achieved, respectively. After 130 days, ARE and TNRE remained stable at 92 and 81.1%, respectively. This indicates a reliable method for achieving rapid start-up and stable operation of the CANON process. Moreover, Candidatus Kuenenia and Candidatus Brocadia were identified as dominant anammox genera on the carrier. Nitrosomonas was the predominant genus among ammonia-oxidizing bacteria. Spatial differences were observed in the microbial population of umbrella BF carriers. This arrangement facilitated autotrophic nitrogen removal in a single reactor. This study indicates that the novel umbrella BF carrier is a highly suitable biocarrier for the CANON process. HIGHLIGHTS The umbrella basalt fiber (BF) carrier CANON reactor achieved rapid start-up and stable operation.; There were spatial distribution differences between AOB and anammox bacteria in the umbrella BF carrier.; Umbrella BF carriers enhance the abundance and diversity of microbial communities.;

Abstract Background It has been proposed that anti-angiogenesis therapy could induce tumor "vascular normalization" and further enhance the efficacy of chemotherapy, radiotherapy, target therapy, and immunotherapy for nearly twenty years. However, the detailed molecular mechanism of this phenomenon is still obscure. Method Overexpression and knockout of CCL28 in human lung adenocarcinoma cell line A549 and murine lung adenocarcinoma cell line LLC, respectively, were utilized to establish mouse models. Single-cell sequencing was performed to analyze the proportion of different cell clusters and metabolic changes in the tumor microenvironment (TME). Immunofluorescence and multiplex immunohistochemistry were conducted in murine tumor tissues and clinical biopsy samples to assess the percentage of pericytes coverage. Primary pericytes were isolated from lung adenocarcinoma tumor tissues using magnetic-activated cell sorting (MACS). These pericytes were then treated with recombinant human CCL28 protein, followed by transwell migration assays and RNA sequencing analysis. Changes in the secretome and metabolome were examined, and verification of retinoic acid metabolism alterations in pericytes was conducted using quantitative real-time PCR, western blotting, and LC–MS technology. Chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR) was employed to validate the transcriptional regulatory ability and affinity of RXRα to specific sites at the ANGPT1 promoter. Results Our study showed that after undergoing anti-angiogenesis treatment, the tumor exhibited a state of ischemia and hypoxia, leading to an upregulation in the expression of CCL28 in hypoxic lung adenocarcinoma cells by the hypoxia-sensitive transcription factor CEBPB. Increased CCL28 could promote tumor vascular normalization through recruiting and metabolic reprogramming pericytes in the tumor microenvironment. Mechanistically, CCL28 modified the retinoic acid (RA) metabolism and increased ANGPT1 expression via RXRα in pericytes, thereby enhancing the stability of endothelial cells. Conclusion We reported the details of the molecular mechanisms of "vascular normalization" after anti-angiogenesis therapy for the first time. Our work might provide a prospective molecular marker for guiding the clinical arrangement of combination therapy between anti-angiogenesis treatment and other therapies.

Abstract The RATIONALE-306 study revealed that patients with advanced or metastatic oesophageal squamous cell carcinoma (OSCC) could benefit from treatment with tislelizumab plus chemotherapy. This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy for treating OSCC from the perspective of the Chinese healthcare system. Partitioned survival model estimated the cost-effectiveness of tislelizumab plus chemotherapy compared with chemotherapy alone for treating OSCC using RATIONALE-306 data. Costs and utilities were obtained from local databases and published studies. Costs, quality-adjusted life-years (QALYs), life-years, incremental cost-effectiveness ratios (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were outcomes. Price simulation were conducted at the willingness-to-pay (WTP) threshold. Sensitivity and subgroup analyses were performed to assess model robustness. Compared with chemotherapy alone, tislelizumab plus chemotherapy yielded an ICER of USD 27,896/QALY, gained an additional 0.414 QALYs and 0.751 life-years, and increased the cost by USD 11,560. Probabilistic sensitivity analysis revealed that tislelizumab plus chemotherapy was cost-effective at the WTP of USD 38,258/QALY with probability of 94.43%. When the price in China was less than USD 3.714 per mg, the price simulation results indicated that tislelizumab plus chemotherapy was cost-effective at a WTP threshold of USD 38,258. Tislelizumab plus chemotherapy yielded an INHB of 0.112 QALYs and an INMB of USD 4,279 compared with chemotherapy alone at a WTP threshold of USD 38,258. Based on the sensitivity analyses, the above results were stable. A general trend was observed for subgroups with better survival benefits related to a higher probability of cost-effectiveness. From the Chinese healthcare perspective, tislelizumab plus chemotherapy is more cost-effective than chemotherapy alone as a first-line therapy for OSCC. These findings can help clinicians make optimal clinical decisions and assist decision-makers in evaluating the cost-effectiveness of tislelizumab in clinical practice.

As the global demand for healthcare services continues to grow, improving the efficiency and effectiveness of the healthcare ecosystem has become a pressing concern. Information systems are transforming the healthcare delivery process, shifting the focus of healthcare services from passive disease treatment to proactive health prevention and the healthcare management model from hospital-centric to patient-centric. This study focuses on reviewing research in IS journals on the topic of e-health and is dedicated to constructing a theoretical model of intelligent health to provide a research basis for future discussions in this field. In addition, as the innovation of intelligent healthcare services has led to changes in its elements (e.g., an increase in the number of stakeholders), there is an urgent need to sort out and analyze the existing research.

Abstract Background Steroid-induced osteonecrosis of femoral head (SONFH) is a severe health risk, and this study aims to identify immune-related biomarkers and pathways associated with the disease through bioinformatics analysis and animal experiments. Method Using SONFH-related datasets obtained from the GEO database, we performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to extract SONFH-related genes. A protein-protein interaction (PPI) network was then constructed, and core sub-network genes were identified. Immune cell infiltration and clustering analysis of SONFH samples were performed to assess differences in immune cell populations. WGCNA analysis was used to identify module genes associated with immune cells, and hub genes were identified using machine learning. Internal and external validation along with animal experiments were conducted to confirm the differential expression of hub genes and infiltration of immune cells in SONFH. Results Differential expression analysis revealed 502 DEGs. WGCNA analysis identified a blue module closely related to SONFH, containing 1928 module genes. Intersection analysis between DEGs and blue module genes resulted in 453 intersecting genes. The PPI network and MCODE module identified 15 key targets enriched in various signaling pathways. Analysis of immune cell infiltration showed statistically significant differences in CD8 + t cells, monocytes, macrophages M2 and neutrophils between SONFH and control samples. Unsupervised clustering classified SONFH samples into two clusters (C1 and C2), which also exhibited significant differences in immune cell infiltration. The hub genes (ICAM1, NR3C1, and IKBKB) were further identified using WGCNA and machine learning analysis. Based on these hub genes, a clinical prediction model was constructed and validated internally and externally. Animal experiments confirmed the upregulation of hub genes in SONFH, with an associated increase in immune cell infiltration. Conclusion This study identified ICAM1, NR3C1, and IKBKB as potential immune-related biomarkers involved in immune cell infiltration of CD8 + t cells, monocytes, macrophages M2, neutrophils and other immune cells in the pathogenesis of SONFH. These biomarkers act through modulation of the chemokine signaling pathway, Toll-like receptor signaling pathway, and other pathways. These findings provide valuable insights into the disease mechanism of SONFH and may aid in future drug development efforts.

Abstract Breast cancer (BRCA) has become the most common type of cancer in women. Improving the therapeutic response remains a challenge. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a classic tumour suppressor with emerging new functions discovered in recent years, and myeloid PTEN loss has been reported to impair antitumour immunity. In this study, we revealed a novel mechanism by which myeloid PTEN potentially affects antitumour immunity in BRCA. We detected accelerated stress granule (SG) assembly under oxidative stress in PTEN-deficient bone marrow-derived macrophages (BMDMs) through the EGR1-promoted upregulation of TIAL1 transcription. PI3K/AKT/mTOR (PAM) pathway activation also promoted SG formation. ATP consumption during SG assembly in BMDMs impaired the phagocytic ability of 4T1 cells, potentially contributing to the disruption of antitumour immunity. In a BRCA neoadjuvant cohort, we observed a poorer response in myeloid PTENlow patients with G3BP1 aggregating as SGs in CD68+ cells, a finding that was consistent with the observation in our study that PTEN-deficient macrophages tended to more readily assemble SGs with impaired phagocytosis. Our results revealed the unconventional impact of SGs on BMDMs and might provide new perspectives on drug resistance and therapeutic strategies for the treatment of BRCA patients.

Abstract Background The heat shock transcription factor (Hsf) is a crucial regulator of plant stress resistance, playing a key role in plant stress response, growth, and development regulation. Results In this study, we utilized bioinformatics tools to screen 25 VbHsf members, which were named VbHsf1-VbHsf25. We used bioinformatics methods to analyze the sequence structure, physicochemical properties, conserved motifs, phylogenetic evolution, chromosome localization, promoter cis-acting elements, collinearity, and gene expression of Hsf heat shock transcription factor family members under low-temperature stress. The results revealed that the majority of the Hsf genes contained motif1, motif2, and motif3, signifying that these three motifs were highly conserved in the Hsf protein sequence of Verbena bonariensis. Although there were some variations in motif deletion among the members, the domain remained highly conserved. The theoretical isoelectric point ranged from 4.17 to 9.71, with 21 members being unstable proteins and the remainder being stable proteins. Subcellular localization predictions indicated that all members were located in the nucleus. Phylogenetic analysis of the Hsf gene family in V. bonariensis and Arabidopsis thaliana revealed that the Hsf gene family of V. bonariensis could be categorized into three groups, with group A comprising 17 members and group C having at least two members. Among the 25 Hsf members, there were 1–3 exons located on seven chromosome fragments, which were unevenly distributed. Collinearity analysis demonstrated the presence of seven pairs of homologous genes in the VbHsf gene family. The Ka/Ks ratios were less than one, indicating that the VbHsf gene underwent purification selection pressure. Additionally, nine genes in V. bonariensis were found to have collinearity with A. thaliana. Promoter analysis revealed that the promoters of all VbHsf genes contained various types of cis-acting elements related to hormones and stress. Based on RNA-seq data, qRT-PCR analysis of six highly expressed genes was performed, and it was found that VbHsf5, VbHsf14, VbHsf17, VbHsf18, VbHsf20 and VbHsf21 genes were highly expressed at 12 h of low-temperature treatment, and the expression decreased after 24 h, among which VbHsf14 was up-regulated at 12 h of low-temperature by 70-fold. Conclusions Our study may help reveal the important roles of Hsf in plant development and show insight for the further molecular breeding of V. bonariensis.

Abstract Background Mesenchymal stem cells (MSCs) are one of the most widely studied adult stem cells, while MSC replicative senescence occurs with serial expansion in vitro. We determined whether miR-34a can regulate MSC senescence by directly targeting glycolytic key enzymes to influence glycolysis. Methods Detected the effects of miR-34a on MSC senescence and glycolytic metabolism through gene manipulation. Bioinformatics prediction and luciferase reporter assay were applied to confirm that HK1 is a direct target of miR-34a. The underlying regulatory mechanism of miR-34a targeting HK1 in MSC senescence was further explored by a cellular function recovery experiment. Results In the current study, we revealed that miR-34a over-expression exacerbated senescence-associated characteristics and impaired glycolytic metabolism. Then we identified hexokinase1 (HK1) as a direct target gene of miR-34a. And HK1 replenishment reversed MSC senescence and reinforced glycolysis. In addition, miR-34a-mediated MSC senescence and lower glycolytic levels were evidently rescued following the co-treatment with HK1 over-expression. Conclusion The miR-34a-HK1 signal axis can alleviate MSC senescence via enhancing glycolytic metabolism, which possibly provides a novel mechanism for MSC senescence and opens up new possibilities for delaying and suppressing the occurrence and development of aging and age-related diseases.

Abstract Background The pathogenesis of diabetic cardiomyopathy is closely linked to abnormal glycosylation modifications. N-acetylglucosaminyltransferase V (GnT-V), which catalyzes the production of N-linked -1–6 branching of oligosaccharides, is involved in several pathophysiological mechanisms of many disorders, including cardiac hypertrophy and heart failure. However, the mechanism by which GnT-V regulates cardiac hypertrophy in diabetic cardiomyopathy is currently poorly understood. In this study, we investigated the role of GnT-V on myocardial hypertrophy in diabetic cardiomyopathy and elucidated the underlying mechanisms. Material and methods Streptozotocin (STZ) was intraperitoneally injected into mice to induce diabetic cardiomyopathy. An adeno-associated virus (AAV) carrying negative control small hairpin RNA (shNC) or GnT-V-specifc small hairpin RNA (shGnT-V) was used to manipulate GnT-V expression. In our study, forty male C57BL/6J mice were randomly divided into four groups (10 mice per group): control mice with AAV-shNC, diabetic cardiomyopathy mice with AAV-shNC, control mice with AAV-shGnT-V, and diabetic cardiomyopathy mice with AAV-shGnT-V. In addition, H9C2 cells and primary neonatal cardiac fibroblasts treated with high glucose were used as a cell model of diabetes. Analysis of cardiac hypertrophy and fibrosis, as well as functional studies, were used to investigate the underlying molecular pathways. Results AAV-mediated GnT-V silencing dramatically improved cardiac function and alleviated myocardial hypertrophy and fibrosis in diabetic mice. In vitro experiments demonstrated that GnT-V was elevated in cardiomyocytes and induced cardiomyocyte hypertrophy in response to high glucose stimulation. GnT-V knockdown significantly reduced the expression of the integrinβ1 signaling pathway, as evidenced by decreased downstream ERK1/2 activity, which inhibited cardiomyocyte hypertrophy accompanied by reduced ANP, BNP, and β-MHC expression. Furthermore, knocking down GnT-V expression lowered the TGF-β1-Smads signaling pathway, which reduced the expression of α-SMA, collagen I, and collagen III. Conclusions Overall, our research indicated that GnT-V may be a useful therapeutic target to treat diabetic cardiomyopathy, primarily in the inhibition of myocardial hypertrophy and fibrosis.

Abstract The enhancement of regional comprehensive development ability is significantly impacted by the study on the implementation effect of regional integration strategies. The integration strategy’s impact on urban development during COVID-19 in the Yangtze River Delta(YRD) is unclear. According to prior industrial transfer theory, Hefei, Anhui’s capital, is difficult to transfer industries, and other YRD cities push industry integration in Anhui. This study employs the theory of economic and land resource use to examine the resilience of the industrial economy during an epidemic by using industrial land as a representation of industrial economic development. The three cities in Anhui—Wuhu, Maanshan, and Chuzhou (Wu-ma-Chu) were selected as the research area. The study employed the UNet deep learning method to detect the land use types in Wu-ma-Chu. The land transfer matrix and the standard deviation ellipse were utilised to research the alterations in industrial land use and the spatial distribution of industrial output value, respectively. The results showed that the industrial land in Machu continued to grow during the outbreak, highlighting the resilience of the region’s industrial economy. During 2019–2022, the elliptical ring of industrial output value is distributed in Nanjing, revealing the radiating role of Nanjing in integrating into the integration of the YRD. This confirms China’s YRD integration strategy, strengthens regional economic resilience, and encourages coordinated regional economic development.

Abstract Objective This study was designed to develop and validate a robust predictive model for one-year mortality in elderly coronary heart disease (CHD) patients with anemia using machine learning methods. Methods Demographics, tests, comorbidities, and drugs were collected for a cohort of 974 elderly patients with CHD. A prospective analysis was performed to evaluate predictive performances of the developed models. External validation of models was performed in a series of 112 elderly CHD patients with anemia. Results The overall one-year mortality was 43.6%. Risk factors included heart rate, chronic heart failure, tachycardia and β receptor blockers. Protective factors included hemoglobin, albumin, high density lipoprotein cholesterol, estimated glomerular filtration rate (eGFR), left ventricular ejection fraction (LVEF), aspirin, clopidogrel, calcium channel blockers, angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), and statins. Compared with other algorithms, an ensemble machine learning model performed the best with area under the curve (95% confidence interval) being 0.828 (0.805–0.870) and Brier score being 0.170. Calibration and density curves further confirmed favorable predicted probability and discriminative ability of an ensemble machine learning model. External validation of Ensemble Model also exhibited good performance with area under the curve (95% confidence interval) being 0.825 (0.734–0.916) and Brier score being 0.185. Patients in the high-risk group had more than six-fold probability of one-year mortality compared with those in the low-risk group (P

Abstract Background The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) method has been used to evaluate glymphatic system function in patients with migraine. However, since the diffusion tensor model cannot accurately describe the diffusion coefficient of the nerve fibre crossing region, we proposed a diffusion kurtosis imaging ALPS (DKI-ALPS) method to evaluate glymphatic system function in patients with migraine. Methods The study included 29 healthy controls and 37 patients with migraine. We used diffusion imaging data from a 3T MRI scanner to calculate DTI-ALPS and DKI-ALPS indices of the two groups. We compared the DTI-ALPS and DKI-ALPS indices between the two groups using a two-sample t-test and performed correlation analyses with clinical variables. Results There was no significant difference in DTI-ALPS index between the two groups. Patients with migraine showed a significantly increased right DKI-ALPS index compared to healthy controls (1.6858 vs. 1.5729; p = 0.0301). There was no significant correlation between ALPS indices and clinical variables. Conclusions DKI-ALPS is a potential method to assess glymphatic system function and patients with migraine do not have impaired glymphatic system function.

Abstract Invasion and migration are the key hallmarks of cancer, and aggressive growth is a major factor contributing to treatment failure and poor prognosis in glioblastoma. Protein arginine methyltransferase 6 (PRMT6), as an epigenetic regulator, has been confirmed to promote the malignant proliferation of glioblastoma cells in previous studies. However, the effects of PRMT6 on glioblastoma cell invasion and migration and its underlying mechanisms remain elusive. Here, we report that PRMT6 functions as a driver element for tumor cell invasion and migration in glioblastoma. Bioinformatics analysis and glioma sample detection results demonstrated that PRMT6 is highly expressed in mesenchymal subtype or invasive gliomas, and is significantly negatively correlated with their prognosis. Inhibition of PRMT6 (using PRMT6 shRNA or inhibitor EPZ020411) reduces glioblastoma cell invasion and migration in vitro, whereas overexpression of PRMT6 produces opposite effects. Then, we identified that PRMT6 maintains the protein stability of EZH2 by inhibiting the degradation of EZH2 protein, thereby mediating the invasion and migration of glioblastoma cells. Further mechanistic investigations found that PRMT6 inhibits the transcription of TRAF6 by activating the histone methylation mark (H3R2me2a), and reducing the interaction between TRAF6 and EZH2 to enhance the protein stability of EZH2 in glioblastoma cells. Xenograft tumor assay and HE staining results showed that the expression of PRMT6 could promote the invasion of glioblastoma cells in vivo, the immunohistochemical staining results of mouse brain tissue tumor sections also confirmed the regulatory relationship between PRMT6, TRAF6, and EZH2. Our findings illustrate that PRMT6 suppresses TRAF6 transcription via H3R2me2a to enhance the protein stability of EZH2 to facilitate glioblastoma cell invasion and migration. Blocking the PRMT6-TRAF6-EZH2 axis is a promising strategy for inhibiting glioblastoma cell invasion and migration.

Abstract The COVID-19 pandemic has had an inestimable impact worldwide, challenging the daily lives and interactions of children and their families. In 2022, Shanghai implemented a three-month lockdown in response to an acceleration of positive cases during the pandemic period. This restrictive policy provided insight into the impact of the lockdown on children's social adjustment and the role of parent–child conflict during this process. Mothers of preschool-aged children participated in this study and completed the Chinese version of Child-Parent Relationship Scale (CPRS) and the Strengths and Difficulties Questionnaire (SDQ). Using Propensity Score Matching (PSM) method, two matched groups were formed: pre-lockdown group and post-lockdown group, with a total of 574 preschoolers (N = 297 in each group; M age = 4.36, SD = 0.86) were recruited. The results showed that the lockdown directly impacted children's emotional symptoms. Additionally, the parent–child conflict mediated relationship between the lockdown and children's adjustment. Specifically, parent–child conflict deteriorated children's emotional symptoms, hyperactivity-attention problems, and prosocial behaviors. These findings highlight the significant impact of the severe lockdown on children's social adjustment and the role of parent–child interactions during this period.

Pseudomyxoma peritonei (PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy (CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit ( GNAS ). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radio-immunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.

Clostridium perfringens (C. perfringens) is an important veterinary pathogen and a noteworthy threat to human and animal health. Recently, there has been a significant rise in the number of moose fatalities caused by this rare, endemic species in China. Currently, there is an increasing trend in conducting whole-genome analysis of C. perfringens strains originating from pigs and chickens, whereas fewer studies have been undertaken on Elaphurus davidianus-originating strains at the whole-genome level. Our laboratory has identified and isolated five C. perfringens type A from affected Elaphurus davidianus. The current study identified the most potent strain of C. perfringens, which originated from Elaphurus davidianus, and sequenced its genome to reveal virulence genes and pathogenicity. Our findings show that strain CX1-4 exhibits the highest levels of phospholipase activity, hemolytic activity, and mouse toxicity compared to the other four isolated C. perfringens type A strains. The chromosome sequence length of the CX1-4 strain was found to be 3,355,389 bp by complete genome sequencing. The current study unveils the genomic characteristics of C. perfringens type A originating from Elaphurus davidianus. It provides a core foundation for further investigation regarding the prevention and treatment of such infectious diseases in Elaphurus davidianus.

Protoplast-based transient gene expression system has been widely used in plant genome editing because of its simple operation and less time-consuming. In order to establish a universal protoplast-based transient transfection system for verifying activities of genome editing vectors containing targets in Brassica, we systematically optimized factors affecting protoplast isolation and transient gene expression. We established an efficient protoplast-based transient gene expression system (PTGE) in Chinese cabbage, achieving high protoplast yield of 4.9 × 105 · g−1 FW, viability over 95%, and transfection efficiency of 76%. We showed for the first time that pretreatment of protoplasts with a hypotonic MMG could significantly enhance the transfection efficiency. Furthermore, protoplasts incubated at 37 °C for 6 min improved the transfection efficiency to 86%. We also demonstrated that PTGE worked well (more than 50% transfection efficiency) in multiple Brassica species including cabbage, Pak Choi, Chinese kale, and turnip. Finally, PTGE was used for validating the activities of CRISPR/Cas9 vectors containing targets in Chinese cabbage, cabbage, and pak choi, demonstrating the broad applicability of the established PTGE for genome editing in Brassica crops.