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Abstract Frequent extreme heat events around the world not only pose a major threat to human health but also cause significant economic losses to the livestock industry. The existing management practices are insufficient to fully prevent heat stress with an urgent need to develop preventive medicines. The aim of this study was to develop an anti-heat stress Chinese herbal formula (CHF) via big data analysis techniques and to evaluate its anti-heat stress effect and mechanism of action via pharmacodynamic evaluation and network pharmacology analysis. Many anti-heat stress CHFs were collected from the Chinese National Knowledge Infrastructure (CNKI) database. Three alternative CHFs were obtained via unsupervised entropy hierarchical clustering analysis, and the most effective CHF against heat stress, Shidi Jieshu decoction (SJD), was obtained by screening in a mouse heat stress model. In dry and hot environments, SJD significantly improved the heat tolerance of AA broilers by 4–6°C. In a humid and hot environment, pretreatment with 2% SJD resulted in 100% survival of Wenchang chickens at high temperatures. The main active ingredients of SJD were identified as muntjacoside E, timosaponin C, macrostemonoside H and mangiferin via ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) and database comparison. The active ingredients of SJD were found to target tumor necrosis factor-α (TNF-α), signal transducer activator of transcription 3 (STAT3) and epidermal growth factor receptor (EGFR). Finally, the safety of the new formulation was assessed in an acute oral toxicity study in rats. The SJDs developed in this study provide a new option for the prevention of heat stress in animal husbandry and offer new insights for further research on anti-heat stress.

The influence of confining pressure on the dynamic fracture mechanical behavior of deep rock masses is crucial in the exploitation of deep resources and the development of underground spaces. In this study, dynamic caustics experiments were conducted using transparent epoxy resin materials to investigate the crack propagation behavior and interaction mechanisms of double cracks under confinement. The experimental results indicate that biaxial confining pressure suppresses crack propagation, interaction between double cracks, and penetration. Without confining pressure, cracks do not penetrate until the relative vertical distance ΔH between crack tips is 20 mm, whereas with confining pressure, cracks cease to penetrate when the relative vertical distance between crack tips is 10 mm; however, interaction between crack tips still exists at this point. During the crack interaction stage, both fracture toughness and propagation velocity of crack tips exhibit significant fluctuations under no confining pressure conditions, whereas under confining pressure, both decrease rapidly. Additionally, under confining pressure conditions, the fluctuation range of crack propagation direction during crack interaction is relatively small. Confining pressure rapidly reduces the degree of stress concentration at crack tips, increases the rate of energy release at crack tips, and enhances the ability of dynamic cracks to resist the influence of other crack tips or crack surfaces. Under confining pressure, continuous Rayleigh waves are typically observed at crack tips due to an imbalance between stored strain energy and the energy release rate. These waves dissipate part of the strain energy, promoting crack deflection and branching.

At present, the operational environment for underwater acoustic contermeasure is increasingly complicated. The emphasis on future underwater warfare is mainly focused on the contermeasure and counter-contermeasure of intelligent underwater unmanned systems. The research on intelligent unmanned undersea vehicle(UUV) recognition and counter-contermeasure capability is of great significance for improving the overall operational effectiveness of intelligent undersea unmanned systems. In order to evaluate the target recognition and counter-contermeasure effectiveness of the intelligent UUVs, the main factors affecting the system effectiveness were analyzed, and the effectiveness index system was established. The evaluation model was also proposed. The weight of the index system was determined by the combination of subjective and objective weighting methods, and the target recognition and counter-contermeasure effectiveness of the intelligent UUVs was evaluated by the improved technique for order preference by similarity to ideal solution(TOPSIS). The evaluation conclusion can provide a reference for the design and optimization of the UUV target recognition and counter-contermeasure system.

Abstract Bacteria-derived H2S plays multifunctional protective roles against antibiotics insult, and the H2S biogenesis pathway is emerging as a viable target for the antibacterial adjuvant design. However, the development of a pan-inhibitor against H2S-synthesizing enzymes is challenging and underdeveloped. Herein, we propose an alternative strategy to downregulate the H2S levels in H2S-producing bacteria, which depletes the bacteria-derived H2S chemically by H2S scavengers without acting on the synthesizing enzymes. After the screening of chemically diversified scaffolds and a structural optimization campaign, a potent and specific H2S scavenger is successfully identified, which displays efficient H2S depletion in several H2S-producing bacteria, potentiates both bactericidal agents and photodynamic therapy, enhances the bacterial clearance of macrophages and polymorphonuclear neutrophils, disrupts the formation of bacterial biofilm and increases the sensitivity of bacterial persister cells to antibiotics. Most importantly, such an H2S scavenger exhibits sensitizing effects with gentamicin in Pseudomonas aeruginosa -infected pneumonia and skin wound female mouse models. In aggregate, our results not only provide an effective strategy to deplete bacteria-derived H2S and establish the H2S biogenesis pathway as a viable target for persisters and drug-resistant bacteria, but also deliver a promising antibacterial adjuvant for potential clinical translation.

Abstract Background Monitoring symptoms is crucial for the early detection of disease progression and timely intervention, which is essential for reducing severe cases and mortality rates in rapidly spreading pandemics, such as COVID-19. Therefore, during infectious disease pandemics, the rapid development of real-time symptom monitoring platforms is essential. This study aimed to explore the urgent development process of an electronic system for patient-reported outcome monitoring in emergency situations. Methods The development of the electronic patient-reported outcome COVID-19 symptom monitoring platform (ePRO-CoV-SM) included the following steps: (1) modifying an electronic patient-reported outcome symptom-reporting platform to assess patients with COVID-19 and validating its feasibility and sensitivity for longitudinal symptom measurement; (2) updating the system to accommodate the newly emerged severe acute respiratory syndrome coronavirus 2 BA.2.2 variant; and (3) applying it in real-world settings. Literature review, expert consultation, and subject-group discussions were used to develop symptom items. Response rate and missing item rate were used as validation indicators for ePRO-CoV-SM. Results The ePRO-CoV-SM (2.0) consists of a core set of symptom items, a WeChat mini program, an online project design backend, a management and communication front, and a database. During the 2020 verification, the response rate of ePRO symptom monitoring reached 89.47% and the item missing rate was 0.33%, the monitoring revealed that a considerable number of asymptomatic patients were experiencing undesirable symptoms during the isolation period. In its real-world application in 2022, the response rate was 85.93% and the item missing rate was 4.84%, the monitoring found the symptom burden was higher in the younger group (18–40 years old) than in the older group (40–67 years old), and over 30% of patients reported symptoms such as cough (36.08%), dry mouth (35.67%), sleep disorders (32.27%), appetite loss (32.17%), and sputum (30.79%) during the isolation period. Conclusions Electronic patient-reported outcome measurement was demonstrated to be sensitive and feasible for monitoring symptoms in patients with COVID-19. By integrating smartphone-based data collection with real-time online data transmission and secure data storage using Secure Sockets Layer encryption, an electronic platform for monitoring critical symptoms can be rapidly established in emergency situations.

The coal resources in western China are mainly Jurassic coal fields, and the Jurassic coal measure strata are generally affected by roof composite water, so the water-rich evaluation of roof sandstone aquifer is the premise of safe mining. Taking Longde Coal Mine as the research object, the pore structure characteristics of sandstone were analyzed through nitrogen adsorption test and whole rock analysis. Based on FHH fractal model, the correlation between fractal dimension and rock composition, pore structure and burial depth was analyzed. The results show that the sandstone in Longde Coal Mine has strong heterogeneity, and the fractal dimension D2 is larger than D1, indicating that the pore structure in the sandstone is more complex than that on the surface. The composition of rock is an important factor affecting the complexity of pores, and clay minerals and quartz are the main factors affecting the fractal dimension. The adsorption hysteresis of sandstone in the region is approximately H3 and H4, mainly narrow and plate-like fissure pores, and micro-medium pores. Sandstone pores have obvious fractal characteristics in phases. The fractal dimension is positively correlated with clay mineral content, quartz, BET specific surface area, illite content and hydraulic radius, weakly positively correlated with the total pore volume of quartz and BJH, and negatively correlated with rock-forming mineral content, potassium feldspar, plagioclase, kaolinite content, average pore size and porosity. There was a weak negative correlation with permeability, but no correlation with chlorite content.

Three new species of Conostigmus Dahlbom, 1858 (Hymenoptera: Megaspilidae), Conostigmus quadripetalus Wang & Chen, sp. nov., Conostigmus electrinus Wang & Chen, sp. nov., Conostigmus acutus Wang & Chen, sp. nov. are characterized and illustrated from China. Conostigmus ampullaceus Dessart, 1997 is redescribed on the basis of 17 specimens and genitalia pictures are provided for the first time.

Abstract Objective Total cavo-pulmonary connection (TCPC) is a palliative treatment for single ventricular malformations. For high-risk patients (preoperative mean pulmonary arterial pressure, mPAP > 15 mmHg), between the inhaled and oral targeted medications, the application of intravenous treprostinil as a bridge therapy to achieve “seamless” management is core postoperative treatment. This study intends to explore the effect of different administration regimens on early postoperative recovery. Methods This was a retrospective cohort study. High-risk pediatric patients (age ≤ 14 years) who underwent TCPC procedure in Fu Wai Hospital from 2015 to 2022 were included. Since the regimen of treprostinil was standardized in our center in 2021, the patients in 2020 and before were included in group 1, patients in 2021 and 2022 were included in group 2. The hemodynamic parameters were compared before and after the maintenance dose of treprostinil. The differences of demographic characteristics, surgical data and postoperative recovery were compared between the two groups. Results A total of 51 pediatric patients were included. Group 1 included 35 patients who received treprostinil at 1–3 postoperative days and an average dose of 12 ± 4 ng/(kg·min). Group 2 included 16 patients who received treprostinil within postoperative 1 day and an average dose of 22 ± 7 ng/(kg·min). There were no significant differences between the two groups in terms of age, weight, preoperative percutaneous oxygen saturation and mPAP, heterotaxy syndrome, TCPC procedure type, other concurrent procedure, cardiopulmonary bypass time and aortic cross-clamp proportion (p > 0.05). After 24 h of treprostinil treatment, the mPAP in group 1 reduced from 17 ± 3 mmHg to 15 ± 2 mmHg (p

Cassava (Manihot esculenta Crantz) is one of the three major potato crops in the world. Consumption of cassava necessitates thermal processing, and the impact of such processing on the physicochemical and structural characteristics of cassava remained unknown. In this paper, three traditional thermal processing methods (boiling, steaming and frying) were used to heat-treat cassava. The physicochemical properties (chemical composition, pasting properties, thermal properties) and structural changes (microstructure, long-range ordering, and short-range ordering) of the processed cassava and untreated cassava was characterized by scanning electron microscopy, Fourier transform infrared spectrometry, X-ray diffractometer, and differential thermal scanning calorimetry. The findings indicated a significant reduction in the total starch content of cassava following diverse heat treatments, accompanied by a notable increase in amylose content (P

In most Ni-free Ti-Nb- and Ti-Zr-based superelastic alloys, large amounts of high-cost and rare elements such as Nb, Ta, Hf and/or Zr are contained, increasing the cost and fabrication difficulty of the alloy. Here, new low-alloy content Ti-Mo-Zr-Sn-Al alloys are developed with large room temperature superelasticity and narrow stress hysteresis for potential biomedical applications. A good combined performance of yield stress (477 MPa) and small stress hysteresis (117 MPa) is achieved at room temperature in Ti-8Mo-6Zr-6Sn-5Al (wt%) alloy showing a recovery strain of 4.4%, which has not been obtained in previously reported Ni-free Ti-Nb, Ti-Zr and Ti-Mo-based superelastic alloy.

Abstract Self‐healing polyurethane diacrylate (PUDA) composites with outstanding thermal conductivity were prepared with variable boron nitride (BN) and a small number of graphene nanoplatelets (GNPs) (1 wt%). The thermal conductivity of PUDA composites containing 1 wt% GNPs and 29 wt% BN reached 1.73 W/(m·K), showing 27.2% increment compared to PUDA composites only with 30 wt% BN. BN and GNPs mutually promoted the dispersion in the PUDA matrix, and the small number of GNPs was enough to bridge the gaps between BN, so that GNPs and BN exerted a synergistic enhancement effect on the thermal conductivity of PUDA composites with a synergistic efficiency of 1.343. The PUDA composites maintained the tensile strength of 8.21 MPa with good electrical insulation (4.55 × 109 Ω cm). The high degrees of recovery of mechanical strength (>90%) and thermal conductivities (>84%) were also realised by the healing effect of the reversible DA reaction. The PUDA composites with excellent comprehensive properties show broad application potential in the thermal management of electronic devices.

We report our progress in the high-temperature superconductor (HTS) Josephson junction fabrication process founded on utilizing a focused helium ion beam damaging technique and discuss the expected device performance attainable with the HTS multi-junction device technology. Both the achievable high value of characteristic voltage \begin{document}$V_c=I_c R_N $\end{document} of Josephson junctions and the ability to design a large number of arbitrary located Josephson junctions allow narrowing the existing gap in design abilities for low-temperature superconductor (LTS) and HTS circuits even with using a single YBa2Cu3O7–x film layer. A one-layer topology of active electrically small antenna is suggested and its voltage response characteristics are considered.

Abstract In order to optimize the design of three-dimensional tubular woven (3DTW), a design method and matrix model of 3DTW were proposed based on normal loom, where 3D woven was used as tube wall and the weaving method of tubular fabric was applied. Herein, 3D woven was used as the tube wall to obtain the face weave diagram, and the back weave diagram was subsequently obtained by the “negative flip” method. According to the method of layering weaving, the structure diagram of 3DTW could be determined. In order to obtain back weave matrix, the elements in the face weave matrix were replaced and reordered by MATLAB function, and Kronecker product operation was used to achieve the proportional embedding of the face and the back weave matrix and the assignment of the face warp by lifting point elements when weaving the back weft. Finally, the weave matrix of 3DTW was obtained. The proposed design method and matrix model can improve the design efficiency and reduce weaving cost of 3DTW, which could provide a reference for the design and preparation of 3DTW.

Abstract Background Depression and anxiety are prevalent after stroke and associated with poor outcomes. We previously co-developed a stroke-specific self-management intervention, HEADS: UP (Helping Ease Anxiety and Depression after Stroke). The two studies reported here aimed to test the feasibility and acceptability of the HEADS: UP course and supporting materials, and research processes ahead of a definitive trial. Methods We recruited community-dwelling stroke survivors (SS) ≥ 3 months post-stroke, with symptoms of mood disorder (Hospital Anxiety and Depression Scale ≥ 8). Participants could ‘enrol’ a family member/ ‘other’ to take part with them, if desired. Study 1 tested HEADS: UP delivered in-person, and informed optimisation of research processes and intervention delivery and materials. In a pragmatic response to Covid-related socialising restrictions, HEADS: UP was then adapted for online delivery, tested in Study 2. The primary outcome (both studies) was the feasibility (acceptability, fidelity) of the intervention and of research processes. Quantitative data (including patient-reported outcome measures (PROMs) assessing mood and quality of life) and qualitative data were collected pre-/post-intervention. Descriptive statistics were used to analyse quantitative data; a thematic framework approach was used to analyse qualitative data. Both studies received ethical approval prior to commencement. Results Study 1 Feasibility: 13 (59.1%) of 22 potentially eligible stroke survivors consented; aged 66 (median, interquartile range (IQR) 14); male (n = 9; 69%); 28 (IQR 34) months post-stroke. Of these, n = 10 (76.9%) completed PROMS pre-intervention; n = 6 (46.2%) post-intervention. Acceptability: Nine (69.2%) of the 13 participants attended ≥ 4 core intervention sessions. Aspects of screening and data collection were found to be burdensome. Study 2 Feasibility: SS n = 9 (41%) of 22 potentially eligible stroke survivors consented; aged 58 years (median; IQR 12); male (n = 4; 44.4%); 23 (IQR 34) months post-stroke. Of these, n = 5 (55.6%) completed PROMS pre-intervention; n = 5 (55.6%) post-intervention. Acceptability: Five (55.6%) of the 9 participants attended ≥ 4 core sessions. They found online screening and data collection processes straightforward.

Abstract Background Everolimus is an effective treatment for renal angiomyolipoma associated with TSC (TSC-RAML). However, its impact on hematologic parameters in TSC-RAML patients remains unclear. Methods Hematologic data were collected from TSC-RAML patients undergoing everolimus treatment in two registered clinical trials. Dynamic changes in hematologic parameters during treatment were analyzed. Additionally, we also explored variations in hematologic impact based on gender and age within the patient population. Result A total of 55 patients from the two clinical trials are included in this analysis. Hemoglobin, white blood cells (WBC), lymphocytes, neutrophils, and platelet showed significant decreases during everolimus treatment (P

To address the requirements for safety enhancement, weight reduction, and emission reduction, a novel transformation-induced plasticity-assisted bainitic ferrite (TBF) steel was processed by involving a pre-quenching (PQ) process. This steel was designed with varying PQ temperatures to achieve different fractions of intercritical ferrite and bainite, and its influence on mechanical properties of TBF steels was thoroughly investigated through tensile tests and hole expansion tests. The results demonstrated that the introduction of high-temperature PQ treatment before heat treatment can dramatically accelerate the formation of austenite during the secondary annealing process, thereby facilitating a more sufficient bainitic transformation in the subsequent isothermal process. With the increase of PQ temperature from 750 to 900 °C, abundant intercritical ferrite was replaced by lathy bainite. In comparison with conventional specimens, the high-temperature PQ treatment could reduce the fraction of intercritical ferrite and martensite-austenite (M-A) islands, in favor of delaying the initiation of microvoid and microcrack and improving local formability. In summary, the P-900 specimen exhibited optimal comprehensive mechanical properties, with the highest yield strength of 657 MPa, ultimate tensile strength of 1081 MPa, elongation of 28.7%, and hole expansion ratio of 35.1%.

Abstract Gastrin is a gastrointestinal peptide hormone that plays an important role in the progression of colorectal cancer (CRC). However, the molecular mechanism remains unclear. In this study, we identified gastrin-related circRNAs via high-throughput sequencing and selected circRNA_0017065 as the research focus. We further studied its specific role and molecular mechanism in the progression of CRC. Knockdown and overexpression of circRNA_0017065 were performed, and the biological function of circRNA_0017065 in CRC progression was studied via in vitro and in vivo functional experiments. The potential downstream target genes were subsequently identified via screening of databases and gene chip data. The expression of circRNA_0017065 in tumour tissues was significantly upregulated compared with that in adjacent normal tissues. In vitro and in vivo functional experiments revealed that the proliferation and migration of CRC cells were significantly suppressed after circRNA_0017065 knockdown, while apoptosis was promoted. After overexpression of circRNA_0017065, the proliferation and migration of CRC cells were significantly promoted, while apoptosis was inhibited. Mechanistic studies revealed that circRNA_0017065 can act as a sponge for miR-3174 and promote CRC progression via the miR-3174/RBFOX2 axis. In general, gastrin-related circRNA_0017065 plays a key role in the occurrence and development of CRC and is expected to be a potential molecular target for the treatment of CRC metastasis.

Abstract The translocation and assembly module (TAM) has been proposed to play a crucial role in the assembly of a small subset of outer membrane proteins (OMPs) in Proteobacteria based on experiments conducted in vivo using tamA and tamB mutant strains and in vitro using biophysical methods. TAM consists of an OMP (TamA) and a periplasmic protein that is anchored to the inner membrane by a single α helix (TamB). Here we examine the function of the purified E. coli complex in vitro after reconstituting it into proteoliposomes. We find that TAM catalyzes the assembly of four model OMPs nearly as well as the β-barrel assembly machine (BAM), a universal heterooligomer that contains a TamA homolog (BamA) and that catalyzes the assembly of almost all E. coli OMPs. Consistent with previous results, both TamA and TamB are required for significant TAM activity. Our study provides direct evidence that TAM can function as an independent OMP insertase and describes a new method to gain insights into TAM function.

Abstract Background The Hippo pathway is a conserved tumour suppressor signalling pathway, and its dysregulation is often associated with abnormal cell growth and tumorigenesis. We previously revealed that the transcriptional coactivator Yes-associated protein (YAP), the key effector of the Hippo pathway, is a molecular target for glioblastoma (GBM), the most common malignant brain tumour. Inhibiting YAP with small interfering RNA (siYAP) or the specific inhibitor verteporfin (VP) can diminish GBM growth to a certain degree. Results In this study, to enhance the anti-GBM effect of siYAP and VP, we designed stepwise-targeting and hypoxia-responsive liposomes (AMVY@NPs), which encapsulate hypoxia-responsive polymetronidazole-coated VP and DOTAP adsorbed siYAP, with angiopep-2 (A2) modification on the surface. AMVY@NPs exhibited excellent blood‒brain barrier crossing, GBM targeting, and hypoxia-responsive and efficient siYAP and VP release properties. By inhibiting the expression and function of YAP, AMVY@NPs synergistically inhibited both the growth and stemness of GBM in vitro. Moreover, AMVY@NPs strongly inhibited the growth of orthotopic U87 xenografts and improved the survival of tumour-bearing mice without adverse effects. Conclusion Specific targeting of YAP with stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and VP efficiently inhibited GBM progression. This study provides a valuable drug delivery platform and creative insights for molecular targeted treatment of GBM in the future.

Abstract Objective To investigate the differential expression genes (DEGs) in spinal tuberculosis using transcriptomics, with the aim of identifying novel therapeutic targets and prognostic indicators for the clinical management of spinal tuberculosis. Methods Patients who visited the Department of Orthopedics at the Second Hospital, Lanzhou University from January 2021 to May 2023 were enrolled. Based on the inclusion and exclusion criteria, there were 5 patients in the test group and 5 patients in the control group. Total RNA was extracted and paired-end sequencing was conducted on the sequencing platform. After processing the sequencing data with clean reads and annotating the reference genome, FPKM normalization and differential expression analysis were performed. The DEGs and long non-coding RNAs (LncRNAs) were analyzed for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. The cis-regulation of differentially expressed mRNAs (DE mRNAs) by LncRNAs was predicted and analyzed to establish a co-expression network. Results This study identified 2366 DEGs, with 974 genes significantly upregulated and 1392 genes significantly downregulated. The upregulated genes are associated with cytokine-cytokine receptor interactions, tuberculosis, and TNF-α signaling pathways, primarily enriched in biological processes such as immunity and inflammation. The downregulated genes are related to muscle development, contraction, fungal defense response, and collagen metabolism processes. Analysis of LncRNAs from bone tuberculosis RNA-seq data detected a total of 3652 LncRNAs, with 356 significantly upregulated and 184 significantly downregulated. Further analysis identified 311 significantly different LncRNAs that could cis-regulate 777 target genes, enriched in pathways such as muscle contraction, inflammatory response, and immune response, closely related to bone tuberculosis. There are 51 genes enriched in the immune response pathway regulated by cis-acting LncRNAs. LncRNAs that regulate immune response-related genes, such as upregulated RP11-451G4.2, RP11-701P16.5, AC079767.4, AC017002.1, LINC01094, CTA-384D8.35, and AC092484.1, as well as downregulated RP11-2C24.7, may serve as potential prognostic and therapeutic targets. Conclusion The DE mRNAs and LncRNAs in spinal tuberculosis are both associated with immune regulatory pathways. These pathways promote or inhibit the tuberculosis infection and development at the mechanistic level and play an important role in the process of tuberculosis transferring to bone tissue.

Abstract Background This study investigates the potential of novel meniscal parameters as predictive factors for incident radiographic knee osteoarthritis (ROA) over a span of four years, as part of the Osteoarthritis Initiative (OAI) study. Objectives Quantitative measurements of meniscal parameters alteration could serve as predictors of OA’s occurrence and progression. Methods and materials A nested matched case-control study design was used to select participants from OAI study. Case knees (n = 178) were defined as those with incident ROA (Kellgren Lawrence Grade (KLG) 0 or 1 at baseline (BL), evolving into KLG 2 or above by year 4). Control knees were matched one-to-one by sex, age and radiographic status with case knees. The mean distance from medial-to-lateral meniscal lesions [Mean(MLD)], mean value of tibial plateau width [Mean(TPW)] and the mean of the relative percentage of the medial-to-lateral meniscal lesions distance [Mean(RMLD)] were evaluated through coronal T2-weighted turbo spin echo (TSE) MRI at P-0 (visit when incident ROA was found on radiograph), P-1(one year prior to P-0) and baseline, respectively. Using the imaging data of one patient, the mechanism was investigated by finite element analysis. Results Participants were on average 60.22 years old, predominantly female (66.7%) and overweight (mean BMI: 28.15). Mean(MLD) and Mean(RMLD) were significantly greater for incident knees compared to no incident knees at baseline, P-1 and P-0. [Mean(MLD), Mean(RMLD); (42.56–49.73) mean ± (7.70–9.52) mm SD vs. (38.14–40.78) mean ± (5.51–7.05)mm SD; (58.61–68.95) mean ± (8.52–11.40) mm SD vs. (52.52–56.35) mean ± (6.53–7.85)mm SD, respectively]. Baseline Mean(MLD) and Mean(RMLD), [Adjusted OR, 95%CI: 1.11(1.07 to 1.16) and 1.13(1.09 to 1.17), respectively], were associated with incident ROA during 4 years, However, Mean(TPW) [Adjusted OR, 95%CI: 0.98(0.94 to 1.02)] was not associated with incident ROA during 4 years. While Mean(TPW) at P-1 and P-0 was not associated with the risk of incident ROA, Mean(MLD) and Mean(RMLD) at P-1 and P-0 were significantly positively associated with the risk of incident ROA. Conclusions The meniscal parameters alteration could be an important imaging biomarker to predict the occurrence of ROA.

Abstract In order to investigate the mechanism of plant growth promoting (PGP) effects of strain Bacillus velezensis WSW007, its PGP traits and production of volatile organic compounds (VOCs) were tested. The effects of VOCs produced by strain WSW007 on plant growth were observed by co-culturing this strain with tobacco seedlings in I-plates. Meanwhile, the effects of VOCs on tobacco gene expression were analysed by a transcriptome analysis and VOCs were identified by solid phase micro extraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS) analysis. As results, strains WSW007 produced acetic acid and siderophore, and could solubilize phosphate; while it also significantly increased the fresh weight of tobacco seedlings via production of VOCs. In transcriptome analysis, plants co-cultured with strain WSW007 presented the highest up-regulated expression for the genes involved in plant growth and development processes, implying that the bacterial VOCs played a role as regulator of plant gene expression. Conclusively, the up-regulation in expression of growth- and development-related genes via VOCs production is an important PGP mechanism in strain B. velezensis WSW007.

Objective: To investigate the effect and mechanism of Hippophae rhamnoides flavone (HRF) on polycystic ovarian syndrome (PCOS) in rats, and to provide new ideas for the prevention and treatment of PCOS. Methods: A PCOS rat model was duplicated by giving rats a high-fat diet combined with the intragastric administration of letrozole, and the model rats were randomly divided into model group, low-dose HRF group (200 mg/kg HRF), high-dose HRF group (400 mg/kg HRF) and metformin group (100 mg/kg). Changes in the related indicators were detected on the 21 d after the rats were administered with the different agents by gavage. Results: Compared with that in the model group, the ovarian index, the percentage of interestrus temporal image, the fasting blood glucose (FBG) level, the fasting insulin (FINS) content, the insulin resistance index (HOMA-IR), the activities of serum luteinizing hormone (LH) and testosterone (T), the levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and C reactive protein (CRP) of rats in low- and high-dose HRF groups were respectively decreased significantly (P

Abstract The mislocalization of proteins leads to breast cancer, one of the world’s most prevalent cancers, which can be identified from immunohistochemical images. Here, based on the deep learning framework, location prediction models were constructed using the features of breast immunohistochemical images. Ultimately, six differentially localized proteins that with stable differentially predictive localization, maximum localization differences, and whose predicted results are not affected by removing a single image are obtained (CCNT1, NSUN5, PRPF4, RECQL4, UTP6, ZNF500). Further verification reveals that these proteins are not differentially expressed, but are closely associated with breast cancer and have great classification performance. Potential mechanism analysis shows that their co-expressed or co-located proteins and RNAs may affect their localization, leading to changes in interactions and functions that further causes breast cancer. They have the potential to help shed light on the molecular mechanisms of breast cancer and provide assistance for its early diagnosis and treatment.

The accurate prediction of aerothermal loads is the basis to guide hypersonic vehicle design. Under the background that classical aerothermal prediction methods are more and more difficult to meet the demand of efficient and accurate aerothermal prediction in engineering, data-driven aerothermal modeling prediction methods have gradually become a new paradigm of aerothermal prediction in recent years. Firstly, the relationship between the data-driven aerothermal modeling prediction method and the classical aerothermal prediction method was described. Then, from the modeling idea, the data-driven aerothermal modeling prediction methods were summarized into three categories: The dimensionality reduction modeling method of feature space, pointwise modeling method and physical information embedding modeling method were introduced and analyzed in detail. It is found that the data-driven aerothermal modeling prediction method is not only more accurate than the engineering algorithm, but also can effectively reduce the workload of test measurement and numerical calculation when combined with the sampling method, and the model given is more efficient and concise. Finally, the development trend of data-driven aerothermal modeling prediction methods was prospected. It is pointed out that the deep combination of data-driven technology and classical aerothermal prediction methods, aerothermal physical information embedding modeling methods and aerothermal prediction big models will be the key points of future research.

Children and adults differ significantly in physiology, biochemistry and immune function, which leads to significant differences in blood transfusion strategies between children and adults. To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children, the National Health Commission organized the formulation and release of the health industry standard Guideline for Pediatric Transfusion (WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard, and explain and interpret the preparation of the " scope", " general provisions" and " factors to consider" of the Standard, hoping to contribute to the understanding and implementation of the Standard.

Abstract Background Lupus nephritis (LN) is the most common cause of kidney injury in systemic lupus erythematosus (SLE) patients and is associated with increased mortality. DNA methylation, one of the most important epigenetic modifications, has been reported as a key player in the pathogenesis of SLE. Hence, our article aimed to explore DNA methylation in CD4+ T cells from LNs to identify additional potential biomarkers and pathogenic genes involved in the progression of LN. Methods Our study enrolled 46 SLE patients with or without kidney injury and 23 healthy controls from 2019 to 2022. CD4+ T cells were sorted for DNA methylation genotyping and RNA-seq. Through bioinformatics analysis, we identified the significant differentially methylated CpG positions (DMPs) only in the LN group and validated them by Bisulfite PCR. Integration analysis was used to screen for differentially methylated and expressed genes that might be involved in the progression of LN, and the results were analyzed via cell experiments and flow cytometry. Results We identified 243 hypomethylated sites and 778 hypermethylated sites only in the LN cohort. Three of these DMPs, cg08332381, cg03297029, and cg16797344, were validated by Bisulfite PCR and could be potential biomarkers for LN. Integrated analysis revealed that the expression of BCL2L14 and IFI27 was regulated by DNA methylation, which was validated by azacytidine (5-aza) treatment. The overexpression of BCL2L14 in CD4+ T cells might induce renal fibrosis and inflammation by regulating the differentiation and function of Tfh cells. Conclusion Our study identified novel aberrant DMPs in CD4+ T cells only in LN patients and DNA methylation-regulated genes that could be potential LN biomarkers. BCL2L14 is likely involved in the progression of LN and might be a treatment target.

Abstract Background The effects of temperature and relative humidity on different types of children’s allergic diseases have not been comprehensively evaluated so far. This study aims to assess the impact of temperature and relative humidity variability on children’s allergic diseases and to identify the critical time window. Methods We collected outpatient data on allergen testing in children between July 2020 and January 2022 from the Affiliated Children’s Hospital of Nanjing Medical University. We defined the 1st, 10th, 90th, and 99th percentiles as extreme cold, moderate cold, moderate hot, and extreme hot for temperature, and as low, moderate high, and extreme high for relative humidity, respectively. A distributed lag nonlinear model (DLNM) combined with a binomial regression model was used to assess the possible nonlinear relationship at different periods. Subgroup analysis by gender and age was conducted. Results We found that extreme and moderate cold temperatures were positively associated with skin allergies and total allergies (28 days: OR = 4.69, 95% CI: 2.88, 7.63; OR = 3.36, 95% CI: 2.39, 4.73) and (28 days: OR = 3.76, CI: 2.43, 5.81; OR = 2.71, 95% CI: 2.00, 3.68), respectively. Moderate and extreme hot temperatures were negatively associated with food allergies (28 days: OR = 0.13, 95% CI: 0.04, 0.41 and OR = 0.04; 95% CI: 0.01, 0.27). Low relative humidity was negatively associated with respiratory allergies, skin allergies, and total allergic diseases (28 days: OR = 0.26, 95% CI: 0.10, 0.71; OR = 0.29, 95% CI: 0.15, 0.55; and OR = 0.42, 95% CI: 0.26, 0.68). Meanwhile, extreme high relative humidity was negatively associated with respiratory allergies, and positively associated with skin allergies, food allergies, and total allergies (28 days: OR = 0.16, 95%CI: 0.07, 0.37; OR = 3.60, 95% CI: 2.52, 5.14; OR = 15.61, 95% CI: 3.23, 75.56; and OR = 2.33, 95% CI: 1.73, 3.15). A stronger relationship between temperature, relative humidity, and allergic diseases was observed in children under 5 years, specifically girls. Conclusions Our study provides evidence that temperature and relative humidity variability may be associated with allergic diseases, however, the directionality of the relationship differs by allergic type.

Abstract Background Olanzapine (OLZ) reverses chronic stress-induced anxiety. Chronic stress promotes cancer development via abnormal neuro-endocrine activation. However, how intervention of brain-body interaction reverses chronic stress-induced tumorigenesis remains elusive. Methods Kras LSL−G12D/WT lung cancer model and LLC1 syngeneic tumor model were used to study the effect of OLZ on cancer stemness and anxiety-like behaviors. Cancer stemness was evaluated by qPCR, western-blotting, immunohistology staining and flow-cytometry analysis of stemness markers, and cancer stem-like function was assessed by serial dilution tumorigenesis in mice and extreme limiting dilution analysis in primary tumor cells. Anxiety-like behaviors in mice were detected by elevated plus maze and open field test. Depression-like behaviors in mice were detected by tail suspension test. Anxiety and depression states in human were assessed by Hospital Anxiety and Depression Scale (HADS). Chemo-sensitivity of lung cancer was assessed by in vivo syngeneic tumor model and in vitro CCK-8 assay in lung cancer cell lines. Results In this study, we found that OLZ reversed chronic stress-enhanced lung tumorigenesis in both Kras LSL−G12D/WT lung cancer model and LLC1 syngeneic tumor model. OLZ relieved anxiety and depression-like behaviors by suppressing neuro-activity in the mPFC and reducing norepinephrine (NE) releasing under chronic stress. NE activated ADRB2-cAMP-PKA-CREB pathway to promote CLOCK transcription, leading to cancer stem-like traits. As such, CLOCK-deficiency or OLZ reverses NE/chronic stress-induced gemcitabine (GEM) resistance in lung cancer. Of note, tumoral CLOCK expression is positively associated with stress status, serum NE level and poor prognosis in lung cancer patients. Conclusion We identify a new mechanism by which OLZ ameliorates chronic stress-enhanced tumorigenesis and chemoresistance. OLZ suppresses mPFC-NE-CLOCK axis to reverse chronic stress-induced anxiety-like behaviors and lung cancer stemness. Decreased NE-releasing prevents activation of ADRB2-cAMP-PKA-CREB pathway to inhibit CLOCK transcription, thus reversing lung cancer stem-like traits and chemoresistance under chronic stress.

Abstract Background Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer worldwide. Therefore, the identification of biomarkers associated with CSCC progression could aid in the early detection of high-risk squamous cell carcinoma and the development of novel therapeutic strategies. Objective This study aimed to investigate the expression patterns of silent mating type Information Regulation 2 homolog 6 (SIRT6) in CSCC and its clinical significance. Methods The protein expression level of SIRT6 in tissues was detected by immunohistochemistry, and the correlation between SIRT6 expression and clinicopathological parameters in CSCC patients was analyzed. The relative expression of SIRT6 in CSCC cell lineage and tissue specimens was determined by western blotting and PCR. The effect of SIRT6 silencing on cell proliferation was evaluated using cell counting kit 8. Wound healing, transwell method, and flow cytometry were used to investigate the migration, invasion, and cell cycle distribution/apoptosis of CSCC cells after SIRT6 silencing, respectively. Western blot was used to detect the expression of EMT (Epithelial-Mesenchymal Transition), cycle, apoptosis, and other related proteins. Results The high expression of SIRT6 was correlated with the location of cancer tissue and Broder staging in CSCC patients. Knockdown of SIRT6 inhibited the proliferation, migration, invasion and EMT of CSCC cells, and promoted their apoptosis, with cells blocked in G1 phase. Study limitations No animal experiments were conducted to further verify the results. Conclusion Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.

Abstract The lack of new drugs that are effective against antibiotic-resistant bacteria has caused increasing concern in global public health. Based on this study, we report development of a modified antimicrobial drug through structure-based drug design (SBDD) and modular synthesis. The optimal modified compound, F8, was identified, which demonstrated in vitro and in vivo broad-spectrum antibacterial activity against drug-resistant bacteria and effectively mitigated the development of resistance. F8 exhibits significant bactericidal activity against bacteria resistant to antibiotics such as methicillin, polymyxin B, florfenicol (FLO), doxycycline, ampicillin and sulfamethoxazole. In a mouse model of drug-resistant bacteremia, F8 was found to increase survival and significantly reduce bacterial load in infected mice. Multi-omics analysis (transcriptomics, proteomics, and metabolomics) have indicated that ornithine carbamoyl transferase (arcB) is a antimicrobial target of F8. Further molecular docking, Isothermal Titration Calorimetry (ITC), and Differential Scanning Fluorimetry (DSF) studies verified arcB as a effective target for F8. Finally, mechanistic studies suggest that F8 competitively binds to arcB, disrupting the bacterial cell membrane and inducing a certain degree of oxidative damage. Here, we report F8 as a promising candidate drug for the development of antibiotic formulations to combat antibiotic-resistant bacteria-associated infections.

Abstract Theretra japonica is an important pollinator and agricultural pest in the family Sphingidae with a wide range of host plants. High-quality genomic resources facilitate investigations into behavioral ecology, morphological and physiological adaptations, and the evolution of genomic architecture. However, chromosome-level genome of T. japonica is still lacking. Here we sequenced and assembled the high-quality genome of T. japonica by combining PacBio long reads, Illumina short reads, and Hi-C data. The genome was contained in 95 scaffolds with an accumulated length of 409.55 Mb (BUSCO calculated a genome completeness of 99.2%). The 29 pseudochromosomes had a combined length of 403.77 Mb, with a mapping rate of 98.59%. The genomic characterisation of T. japonica will contribute to further studies for Sphingidae and Lepidoptera.

Abstract The Span-based model can effectively capture the complex entity structure in the text, thus becoming the mainstream model for nested named entity recognition (Nested NER) tasks. However, traditional Span-based models decode each entity span independently. They do not consider the semantic connections between spans or the entities’ positional information, which limits their performance. To address these issues, we propose a Bi-Directional Context-Aware Network (Bi-DCAN) for the Nested NER. Specifically, we first design a new span-level semantic relation model. Then, the Bi-DCAN is implemented to capture this semantic relationship. Furthermore, we incorporate Rotary Position Embedding into the bi-affine mechanism to capture the relative positional information between the head and tail tokens, enabling the model to more accurately determine the position of each entity. Experimental results show that compared to the latest model Diffusion-NER, our model reduces 20M parameters and increases the F1 scores by 0.24 and 0.09 on the ACE2005 and GENIA datasets respectively, which proves that our model has an excellent ability to recognise nested entities.

Abstract A climatology of stratospheric gravity waves (SGWs) induced by tropical cyclones (TC-SGWs) is necessary for stratospheric aviation safety and accurate numerical weather prediction. Few previous works have characterized the climatology of TC-SGWs, and the relative importance of the source and background wind for TC-SGWs has not been clearly established. Here we present the distribution of TC-SGWs formed over the northwest Pacific Ocean based on 30 years of ERA5 reanalysis data. Using explainable artificial intelligence, we found the background wind in the lower stratosphere to be more important than TCs in controlling the distribution pattern of TC-SGWs. The background wind shear can influence the direction of TC-SGW propagation by refraction and filtering, which influences the distribution pattern of the TC-SGWs. The TC intensity only influences the TC-SGW intensity. Our results provide information on TC-SGW hotspots and suggest the importance of the background wind shear.

Abstract T-cell receptor (TCR) detection can examine the extent of T-cell immune responses. Therefore, the article analyzed characteristic data of glioma obtained by DNA-based TCR high-throughput sequencing, to predict the disease with fewer biomarkers and higher accuracy. We downloaded data online and obtained six TCR-related diversity indices to establish a multidimensional classification system. By comparing actual presence of the 602 correlated sequences, we obtained two-dimensional and multidimensional datasets. Multiple classification methods were utilized for both datasets with the classification accuracy of multidimensional data slightly less to two-dimensional datasets. This study reduced the TCR β sequences through feature selection methods like RFECV (Recursive Feature Elimination with Cross-Validation). Consequently, using only the presence of these three sequences, the classification AUC value of 96.67% can be achieved. The combination of the three correlated TCR clones obtained at a source data threshold of 0.1 is: CASSLGGNTEAFF_TRBV12_TRBJ1-1, CASSYSDTGELFF_TRBV6_TRBJ2-2, and CASSLTGNTEAFF_TRBV12_TRBJ1-1. At 0.001, the combination is: CASSLGETQYF_TRBV12_TRBJ2-5, CASSLGGNQPQHF_TRBV12_TRBJ1-5, and CASSLSGNTIYF_TRBV12_TRBJ1-3. This method can serve as a potential diagnostic and therapeutic tool, facilitating diagnosis and treatment of glioma and other cancers.

Abstract Background Although most children with febrile seizures (FS) have a favorable prognosis, some experience recurrence within 1–3 years. Age, peak temperature, and family history are now recognized as important risk factors for FS recurrence, yet studies in this area are lacking in China. This study aimed to investigate the risk factors for FS recurrence in children in Nantong, China, and to develop a prediction model. Methods This retrospective cohort study analyzed 463 children diagnosed with febrile seizures (FS) who presented to the Affiliated Hospital of Nantong University between January 2015 and June 2020. Basic information, disease characteristics, and laboratory and imaging data were collected. A follow-up survey was conducted one year post-discharge to assess the recurrence status of FS in children. Univariate logistic regression and random forest models were used to identify and rank the predictive ability of risk factors for recurrence. Results Of the 463 children with FS, 70 experienced recurrences within 1 year of discharge, resulting in a one-year recurrence rate of 15%. Age (OR = 0.61, 95% CI: 0.46, 0.80, P

Abstract The proposed method for joint entity and relation extraction integrates the tasks of entity extraction and relation classification by sharing the encoding layer. However, the method faces challenges due to incongruities in the contextual information captured by these subtasks, resulting in potential feature conflicts and adverse effects on model performance. To address this, we introduced a novel joint entity and relation extraction method that incorporates multi-module feature information enhancement (MFIE) ( https://github.com/liyao345496280/Relation-extraction ). We employ a relation awareness enhancement module for the entity extraction task, which directs the model’s focus towards extracting entities closely related to potential relations using a potential relation extraction module and an attention mechanism. For the relation extraction task, we implement an entity information enhancement module that uses entity extraction results to augment the original feature information through a gating mechanism, thereby enhancing relation classification performance. Experiments on the NYT and WebNLG datasets demonstrate that our method performs well. Compared to the state-of-the-art method, the F1 score on the NYT dataset improved by 0.7%.

This study aimed to systematically evaluate the efficacy of liraglutide in treating type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) by comparing liraglutide with placebo or other drugs (mainly insulin). The PubMed, Web of Science, and National Library of Medicine databases were systematically searched from their inception until December 1, 2023. A meta-analysis was performed using Stata 15.1 software. A total of 12 studies with 13 outcome measures were included. The meta-analysis results revealed that liraglutide significantly reduced body mass index (mean difference [MD] = –1.06, 95%CI: –1.41, –0.70, p < 0.001), triglycerides (MD = –0.35, 95%CI: –0.61, –0.09, p = 0.0009), visceral adipose tissue (MD = –21.06, 95%CI: –34.58, –7.55, p = 0.002), and subcutaneous adipose tissue (MD = –20.53, 95%CI: –29.15, –11.90, p < 0.001) levels in patients with T2DM and NAFLD. Of the 11 studies, 2 reported the occurrence of adverse reactions, which were primarily gastrointestinal. Compared with placebo and other drugs (e.g., insulin), liraglutide may improve glucose metabolism, lipid and liver function parameters, and visceral and subcutaneous fat in patients with T2DM and NAFLD, thus constituting an effective treatment for these patients.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis caused by the SFTS virus (SFTSV). Understanding the prevalence of SFTSV RNA in humans, vertebrate hosts and ticks is crucial for SFTS control. Methods A systematic review and meta-analysis were conducted to determine the prevalence of SFTSV RNA in humans, vertebrate hosts and questing ticks. Nine electronic databases were searched for relevant publications, and data on SFTSV RNA prevalence were extracted. Pooled prevalence was estimated using a random effects model. Subgroup analysis and multivariable meta-regression were performed to investigate sources of heterogeneity. Results The pooled prevalence of SFTSV RNA in humans was 5.59% (95% confidence interval [CI] 2.78–9.15%) in those in close contact (close contacts) with infected individuals (infected cases) and 0.05% (95% CI 0.00–0.65%) in healthy individuals in endemic areas. The SFTSV infection rates in artiodactyls (5.60%; 95% CI 2.95–8.96%) and carnivores (6.34%; 95% CI 3.27–10.23%) were higher than those in rodents (0.45%; 95% CI 0.00–1.50%). Other animals, such as rabbits, hedgehogs and birds, also played significant roles in SFTSV transmission. The genus Haemaphysalis was the primary transmission vector, with members of Ixodes, Dermacentor, and Amblyomma also identified as potential vectors. The highest pooled prevalence was observed in adult ticks (1.03%; 95% CI 0.35–1.96%), followed by nymphs (0.66%; 95% CI 0.11–1.50%) and larvae (0.01%; 95% CI 0.00–0.46%). The pooled prevalence in ticks collected from endemic areas (1.86%; 95% CI 0.86–3.14%) was higher than that in ticks collected in other regions (0.41%; 95% CI 0.12–0.81%). Conclusions Latent SFTSV infections are present in healthy individuals residing in endemic areas, and close contacts with SFTS cases are at a significantly higher risk of infection. The type of animal is linked to infection rates in vertebrate hosts, while infection rates in ticks are associated with the developmental stage. Further research is needed to investigate the impact of various environmental factors on SFTSV prevalence in vertebrate hosts and ticks. Graphical Abstract

Abstract Background p53, the most frequently mutated gene in cancer, lacks effective targeted drugs. Methods We developed monoclonal antibodies (mAbs) that target a p53 hotspot mutation E285K without cross-reactivity with wild-type p53. They were delivered using lipid nanoparticles (LNPs) that encapsulate DNA plasmids. Western blot, BLI, flow cytometry, single-cell sequencing (scRNA-seq), and other methods were employed to assess the function of mAbs in vitro and in vivo. Results These LNP-pE285K-mAbs in the IgG1 format exhibited a robust anti-tumor effect, facilitating the infiltration of immune cells, including CD8+ T, B, and NK cells. scRNA-seq revealed that IgG1 reduces immune inhibitory signaling, increases MHC signaling from B cells to CD8+ T cells, and enriches anti-tumor T cell and B cell receptor profiles. The E285K-mAbs were also produced in the dimeric IgA (dIgA) format, whose anti-tumor activity depended on the polymeric immunoglobulin receptor (PIGR), a membrane Ig receptor, whereas that of IgG1 relied on TRIM21, an intracellular IgG receptor. Conclusions Targeting specific mutant epitopes using DNA-encoded and LNP-delivered mAbs represents a potential precision medicine strategy against p53 mutants in TRIM21- or PIGR-positive cancers.

Abstract Background Terpenes are important components of plant aromas, and terpene synthases (TPSs) are the key enzymes driving terpene diversification. In this study, we characterized the volatile terpenes in five different Chrysanthemum nankingense tissues. In addition, genome-wide identification and expression analysis of TPS genes was conducted utilizing an improved chromosome-scale genome assembly and tissue-specific transcriptomes. The biochemical functions of three representative TPSs were also investigated. Results We identified tissue-specific volatile organic compound (VOC) and volatile terpene profiles. The improved Chrysanthemum nankingense genome assembly was high-quality, including a larger assembled size (3.26 Gb) and a better contig N50 length (3.18 Mb) compared to the old version. A total of 140 CnTPS genes were identified, with the majority representing the TPS-a and TPS-b subfamilies. The chromosomal distribution of these TPS genes was uneven, and 26 genes were included in biosynthetic gene clusters. Closely-related Chrysanthemum taxa were also found to contain diverse TPS genes, and the expression profiles of most CnTPSs were tissue-specific. The three investigated CnTPS enzymes exhibited versatile activities, suggesting multifunctionality. Conclusions We systematically characterized the structure and diversity of TPS genes across the Chrysanthemum nankingense genome, as well as the potential biochemical functions of representative genes. Our results provide a basis for future studies of terpene biosynthesis in chrysanthemums, as well as for the breeding of improved chrysanthemum varieties.

Abstract Background This study sought to investigate the prognostic value of basement membrane (BM)-associated gene expressions in oral cancer. Methods We harvested and integrated data on BM-associated genes (BMGs), the oral cancer transcriptome, and clinical information from public repositories. After identifying differentially expressed BMGs, we used Cox and Lasso regression analyses to create a BMG-based risk score for overall survival at various intervals. We then validated this score using the GSE42743 cohort as a validation set. The prognostic potential of the risk scores and their relations to clinical features were assessed. Further, we conducted functional pathway enrichment, immune cell infiltration, and immune checkpoint analyses to elucidate the immunological implications and therapeutic potential of the BMG-based risk score and constituent genes. To confirm the expression levels of the BMG LAMA3 in clinical samples of oral cancer tissue, we performed quantitative real-time PCR (qRT-PCR) and immunohistochemical staining. Results The BMGs LAMA3, MMP14, and GPC2 demonstrated notable prognostic significance, facilitating the construction of a BMG-based risk score. A higher risk score derived from BMGs correlated with a poorer survival prognosis for oral cancer patients. Moreover, the risk-associated BMGs exhibited a significant relationship with immune function variability (P

Abstract The secretagogin (SCGN) was originally identified as a secreted calcium-binding protein present in the cytoplasm. Recent studies have found that SCGN has a close relationship with cancer. However, its role in the occurrence, progression, and prognosis of clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, we utilized a mutual authentication method based on public databases and clinical samples to determine the role of SCGN in the progression and prognosis of ccRCC. Firstly, we comprehensively analyzed the expression characteristics of SCGN in ccRCC in several public databases. Subsequently, we systematically evaluated SCGN expression on 252 microarrays of ccRCC tissues from different grades. It was found that SCGN was absent in all the normal kidney tissues and significantly overexpressed in ccRCC tumor tissues. In addition, the expression level of SCGN gradually decreased with an increase in tumor grade, and the percentage of SCGN staining positivity over 50% was 86.7% (13/15) and 73.4% (58/79) in Grade1 and Grade2, respectively, while it was only 8.3% (12/144) in Grade3, and the expression of SCGN was completely absent in Grade4 (0/14) and distant metastasis group (0/4). Additionally, the expression of SCGN was strongly correlated with the patient's prognosis, with the higher the expression levels of SCGN being associated with longer overall survival and disease-free survival of patients. In conclusion, our results suggest that reduced expression of SCGN in cancer cells is correlated with the progression and prognosis of ccRCC.

Abstract The demand for innovative thermal management materials with superior thermal conductivity and electrical insulating properties has significantly increased with the development of portable and flexible electronic gadgets. Fluorinated graphene (FG) has recently attracted the attention of the scientific community because of its exceptional thermal conductivity and electrical insulating qualities. This work aims to provide a detailed analysis of the structure‐property relationships inherent in FG, including both chemical and physical properties, and to explain the FG manufacturing process. Special attention should be paid to a thorough analysis of the thermodynamic conduction mechanism exhibited by FG, including the effects of corrugation size, fluorine coverage, and fluorine atom distribution on its thermal conductivity. The essay also examines in‐depth the most current and cutting‐edge developments addressing the utilisation of FG as a functional filler in composite‐modified polyimide (PI) materials. Furthermore, it has been noted as a crucial component in answering the needs for possible applications by maximising thermal conductivity and mechanical qualities in FG/PI composites through particular FG structural engineering and increased FG‐PI interaction. As a result, these elements serve as the main focus of ongoing research projects, highlighting important directions for development and investigation.

Background Minimally invasive surgery (MIS) such as minimally invasive chevron osteotomy and Akin osteotomy (MICA) has become popular in the treatment of hallux valgus. However, how to correct three‐dimensional deformities in hallux valgus effectively and simply in MICA is still difficult. Special equipment is required in MICA as has been reported before. It is meaningful and necessary to reduce the reliance on special equipment in MICA. Methods From January 2021 to July 2022, patients with mild or moderate hallux valgus were treated with a joy‐stick assistant three‐dimensional modified technique (Joy‐stick 3D technique) of MIS. VAS, AOFAS Hallux MTP‐IP scores, hallux valgus angle (HVA), intermetatarsal angle (IMA), and distal metatarsal articular angle (DMAA) were measured pre‐ and postoperatively at the last follow‐up of at least 6 months. Scores and radiologic angles were compared using paired sample t‐test. Results A total of 36 cases were included. HVA, IMA, and DMAA were (22.3 ± 6.1)°, (14.0 ± 3.2)°, and (8.9 ± 3.2)° preoperatively, and decreased to (7.0 ± 1.8)°, (3.7 ± 1.0)°, and (3.3 ± 1.1)° postoperatively. VAS decreased from 4.3 ± 1.7 to 0.7 ± 0.7. AOFAS Hallux MTP‐IP scores improved from 68.6 ± 7.6 to 92.9 ± 6.1. Comparing mild and moderate cases, though HVA, IMA, and DMAA were significantly different preoperatively, the angles became statistically similar after surgery. Conclusions A joy‐stick assistant three‐dimensional modified technique is proposed to control the three‐dimensional position of the metatarsal head and to reduce dependence on special tools. Mild and moderate hallux valgus deformities are effectively corrected using Joy‐stick 3D technique.

Diethylstilbestrol (DES), a synthetic non-steroid estrogen, it has been prohibited from being added to animal feed for any purposes. Herein, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) based on a specific monoclonal antibody (mAb) was developed for the rapid screening of DES. Primarily, conjugates of mono-O-3-carboxypropyl diethylstilbestrol with keyhole limpet hemocyanin were used to raise a specific mAb, 1B7, which had IC50 value for DES of 213.0 ng L−1. The limits of detection and limits of quantification value for DES in animal-derived foods ranged from 68.1 to 103.1 ng L−1 and 100.8–192.7 ng L−1, respectively. The DES recovery ranged from 70.1 % to 103.1 %, with coefficients of variation below 13.9 %. A positive correlation (R2 = 0.997) was observed between the results of ic-ELISA and HPLC-MS/MS for milk. In order to inspect its detection effect, milk and animal-derived foods were chosen as the testing object. The results showed that this ic-ELISA method (specific mAb, 1B7) can effectively examine for DES residues.

BackgroundParticulate matter pollution (PMP) is a major global health concern, with the older adult being particularly vulnerable. This study aimed to analyze global trends in PMP-related deaths and disability-adjusted life years (DALYs) among the older adult from 1991 to 2021.MethodsUsing data from the Global Burden of Disease Study 2021, we examined the impacts of ambient particulate matter pollution (APMP) and household air pollution from solid fuels (HAP-SF). We analyzed trends across different regions, socioeconomic development levels, age groups, and genders.ResultsAPMP-related older adult deaths increased from 1,745,000 to 3,850,000, and DALYs from 32,000,000 to 70,000,000. However, age-standardized mortality rate decreased from 384 to 337 per 100,000. HAP-SF-related deaths decreased from 2,700,000 to 2,100,000, and DALYs from 54,000,000 to 42,000,000. Age-standardized mortality rate for HAP-SF declined from 580 to 188 per 100,000. High APMP burden was concentrated in Asia, Africa, and the Middle East, while high HAP-SF burden was found in parts of Africa and South Asia. East Asia had the highest APMP-related older adult deaths (1,680,000) with an age-standardized mortality rate (ASMR) of 619 per 100,000. For HAP-SF, South Asia bore the heaviest burden with 1,020,000 deaths and an ASMR of 616 per 100,000. Females consistently experienced higher age-standardized DALYs rate than males for both APMP and HAP-SF across all regions and years. APMP burden showed a weak negative correlation with the Socio-demographic Index (SDI) at the regional level (r = −0.25, p

IntroductionTomato leaf pests and diseases pose a significant threat to the yield and quality of Q6 tomatoes, highlighting the necessity for comprehensive studies on effective control methods.MethodsCurrent control measures predominantly rely on experience and manual observation, hindering the integration of multi-source data. To address this, we integrated information resources related to tomato leaf pests and diseases from agricultural standards documents, knowledge websites, and relevant literature. Guided by domain experts, we preprocessed this data to construct a sample set.ResultsWe utilized the Named Entity Recognition (NER) model ALBERT-BiLSTM-CRF to conduct end-to-end knowledge extraction experiments, which outperformed traditional models such as 1DCNN-CRF and BiLSTM-CRF, achieving a recall rate of 95.03%. The extracted knowledge was then stored in the Neo4j graph database, effectively visualizing the internal structure of the knowledge graph.DiscussionWe developed a digital diagnostic system for tomato leaf pests and diseases based on the knowledge graph, enabling graphical management and visualization of pest and disease knowledge. The constructed knowledge graph offers insights for controlling tomato leaf pests and diseases and provides new research directions for pest control in other crops.

ObjectiveThis study aimed to analyze the clinical characteristics and prognosis of patients with autoimmune encephalitis (PWAE) who experienced seizures during the acute phase.MethodsClinical data were collected from 84 patients diagnosed with AE at the General Hospital of Ningxia Medical University between January 2015 and January 2023. Patients were divided into seizure and non-seizure groups. Clinical characteristics of both groups were compared, including differences between anti-NMDAR and anti-LGI1 encephalitis within the seizure group. Due to the limited sample size and to avoid overfitting, we focused on univariate logistic regression analysis to identify individual prognostic factors.ResultsA total of 84 patients were enrolled, with 76.19% (64/84) in the seizure group and 23.81% (20/84) in the non-seizure group. The seizure group had a longer hospital stay (p = 0.013), higher rates of impaired consciousness (p = 0.001), and more frequent intensive care unit (ICU) admission (p = 0.011). They also had higher peripheral blood neutrophil-to-lymphocyte ratio (NLR), leukocyte count, and uric acid levels (p = 0.038, p = 0.006, p = 0.020), and were more likely to show slow-wave rhythms on electroencephalography (EEG) (p = 0.031). At 2-year follow-up, there was no significant difference in prognosis between the seizure and non-seizure groups (p = 0.653), with 35.94% (23/64) of the seizure group having a poor prognosis. Status epilepticus (SE), complications, endotracheal intubation, mRS score at discharge, APE2, and RITE2 scores increased the risk of poor prognosis (OR > 1), while intensive care and albumin reduced the risk (OR

Abstract Background Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, but the molecular mechanisms underlying IBD are incompletely understood. In this study, we explored the role and regulating mechanism of otubain 2 (OTUB2), a deubiquitinating enzyme, in IBD. Methods To study the function of OTUB2 in IBD, we generated Otub2–/– mice and treated them with dextran sulfate sodium (DSS) to induce experimental colitis. Bone marrow transplantation was performed to identify the cell populations that were affected by OTUB2 in colitis. The molecular mechanism of OTUB2 in signal transduction was studied by various biochemical methods. Results OTUB2 was highly expressed in colon‐infiltrating macrophages in both humans with IBD and mice with DSS‐induced experimental colitis. Colitis was significantly aggravated in Otub2–/– mice and bone marrow chimeric mice receiving Otub2–/– bone marrow. OTUB2‐deficiency impaired the production of cytokines and chemokines in macrophages in response to the NOD2 agonist muramyl dipeptide (MDP). Upon MDP stimulation, OTUB2 promoted NOD2 signaling by stabilizing RIPK2. Mechanistically, OTUB2 inhibited the proteasomal degradation of RIPK2 by removing K48‐linked polyubiquitination on RIPK2, which was mediated by the active C51 residue in OTUB2. In mice, OTUB2 ablation abolished the protective effects of MDP administration in colitis. Conclusion This study identified OTUB2 as a novel regulator of intestinal inflammation.