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Abstract To investigate mRNA Expression profile and associated signaling pathways in the treatment of diabetic foot ulcer healing by tibial cortex transverse distraction. Tissue samples were collected from the wound edge before and after the surgery. After reference genome transcriptome sequencing and subsequent bioinformatics analysis, the differentially expressed genes and related pathways were explored, and functional analysis of important genes and pathways was conducted. qRT-PCR was used to verify the significantly expressed genes-HLA-DRB1, HLA-DRB5, CXCL5 and IGFL1. There were 2441 significantly up-regulated and 3904 significantly down-regulated genes in the postoperative group. The qRT-PCR results showed the expression of HLA-DRB1, HLA-DRB5 and CXCL5 was consistent with the transcriptional sequencing results. CXCL5 and CXCL6 differentially up-regulated genes are involved in the process of neovascularization, and HLA-DRB1 is involved in the improvement of the degree of diabetic peripheral nerve degeneration. Pathway analysis showed that differential genes were most significantly enriched in Adherens junction, Inflammatory mediator regulation of TRP channels and Wnt signaling pathway. Inflammatory mediator regulation of TRP channels is involved in the improvement of peripheral neurodegeneration, VEGF signaling pathway is involved in the process of neovascularization, and Wnt signaling pathway is involved in the process of bone healing. Significantly up-regulated CXCL5 and CXCL6 and enriched VEGF signaling pathway analyzed are involved in postoperative lower limb neovascularization. The HLA-DRB1 and the enriched Inflammatory mediator regulation of TRP channels may be related to the improvement of postoperative peripheral neurodegeneration. The differentially expressed genes and related pathways can provide objective basis for further mechanism study.

Abstract Direct current microgrid (DCMG) clusters are gaining popularity in power systems due to their simplicity and high efficiency. However, DCMG clusters are susceptible to minor disturbances due to low system inertia. This paper proposes a method to enhance the small‐signal stability of a DCMG cluster by optimizing the main control parameters of the system. This paper presents a small‐signal state‐space model of a DCMG cluster system at the system level, considering a multi‐bus network topology. Then, the control parameters that significantly affect the small‐signal stability of the DCMG are selected using the participation factor method. To enhance the system damping, the Pareto‐optimal frontier of the bi‐objective problem was determined using the elite non‐dominated sorting genetic algorithm (NSGA‐II). The optimal compromise is determined by using the fuzzy membership function method to extract it from the generated Pareto optimal front. The proposed method has been verified on a three‐sub DCMG test system with droop control.

Abstract The global scenario on PVC plasticizer is experiencing a drastic change from petroleum-based, toxic di-(2-ethylhexyl) phthalate (DEHP) toward renewable, non-toxic bio-alternatives. However, replacing diisodecyl phthalate (DIDP), a DEHP analogue specifically intended for plasticizing PVC automotive upholstery, with bio-alternative remains a challenge as few bio-plasticizer volatilizes from PVC as slowly as DIDP, a crucial aspect compulsorily required by automotive industry. Here, we demonstrate that covalently attaching two short esters at the α-position of all components of a traditional epoxidized fatty acid methyl ester via a two-step, hydrogen-to-ester nucleophilic substitution in a one-pot procedure yields an epoxidized fatty acid tri-ester bio-plasticizer with remarkably suppressed volatilization from PVC, and hence an extremely low fogging value comparable to DIDP. With this strategy in hand, DIDP, long deemed irreplaceable despite its toxicity and non-renewable nature, may ultimately be phased out. Graphical Abstract

Objectives: Patients with intermediate or advanced hepatocellular carcinoma (HCC) require repeated disease monitoring, prognosis assessment and treatment planning. In 2018, a novel machine learning methodology “survival path” (SP) was developed to facilitate dynamic prognosis prediction and treatment planning. One year after, a deep learning approach called Dynamic Deephit was developed. The performance of the two state-of-art models in dynamic prognostication have not been compared. Methods: We trained and tested the SP and Dynamic DeepHit models in a large cohort of 2511 HCC patients using time-series data. The time-series data were converted into data of time slices, with an interval of three months. The time-dependent c-index for OS at given prediction time ( t = 1, 6, 12, 18 months) and evaluation time (∆ t = 3, 6, 9, 12, 18, 24, 36, 48 months) were compared. Results: The comparison between SP model and Dynamic DeepHit-HCC model showed the latter had significant better performance at the time of initial admission. The time-dependent c-index of Dynamic DeepHit-HCC model gradually decreased with the extension of time (from 0.756 to 0.639 in the training set; from 0.787 to 0.661 in internal testing set; from 0.725 to 0.668 in multicenter testing set); while the time-dependent c-index of SP model displayed an increased trend (from 0.665 to 0.748 in the training set; from 0.608 to 0.743 in internal testing set; from 0.643 to 0.720 in multicenter testing set). When the prediction time comes to 6 months or later since initial treatment, the survival path model outperformed the dynamic DeepHit model at late evaluation times (∆ t > 12 months). Conclusions: This research highlighted the unique strengths of both models. The SP model had advantage in long term prediction while the Dynamic DeepHit-HCC model had advantages in prediction at near time points. Fine selection of models is needed in dealing with different scenarios.

Abstract The main challenge for immune checkpoint blockade (ICB) therapy lies in immunosuppressive tumor microenvironment (TME). Repolarizing M2‐like tumor‐associated macrophages (TAMs) into inflammatory M1 phenotype is a promising strategy for cancer immunotherapy. Here, this study shows that the tumor suppressive protein SHISA3 regulates the antitumor functions of TAMs. Local delivery of mRNA encoding Shisa3 enables cancer immunotherapy by reprogramming TAMs toward an antitumoral phenotype, thus enhancing the efficacy of programmed cell death 1 (PD‐1) antibody. Enforced expression of Shisa3 in TAMs increases their phagocytosis and antigen presentation abilities and promotes CD8+ T cell‐mediated antitumor immunity. The expression of SHISA3 is induced by damage/pathogen‐associated molecular patterns (DAMPs/PAMPs) in macrophages via nuclear factor‐κB (NF‐κB) transcription factors. Reciprocally, SHISA3 forms a complex with heat shock protein family A member 8 (HSPA8) to activate NF‐κB signaling thus maintaining M1 polarization of macrophages. Knockout Shisa3 largely abolishes the antitumor efficacy of combination immunotherapy with Toll‐like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) and PD‐1 antibody. It further found that higher expression of SHISA3 in antitumoral TAMs is associated with better overall survival in lung cancer patients. Taken together, the findings describe the role of SHISA3 in reprogramming TAMs that ameliorate cancer immunotherapy.

The efficacy of PD-1 therapy in non-small cell lung cancer (NSCLC) patients remains unsatisfactory. Activating the STING pathway is a promising strategy to improve PD-1 inhibitor efficacy. Here, we found tetrandrine (TET), an anti-tumor compound extracted from a medicinal plant commonly used in traditional Chinese medicine, has the ability to inhibit NSCLC tumor growth. Mechanistically, TET induces nuclear DNA damage and increases cytosolic dsDNA, thereby activating the STING/TBK1/IRF3 pathway, which in turn promotes the tumor infiltration of dendritic cells (DCs), macrophages, as well as CD8+ T cells in mice. In vivo imaging dynamically monitored the increased activity of the STING pathway after TET treatment and predicted the activation of the tumor immune microenvironment. We further revealed that the combination of TET with αPD-1 monoclonal antibody (αPD-1 mAb) yields significant anti-cancer effects by promoting CD8+ T cell infiltration and enhancing its cell-killing effect, which in turn reduced the growth of tumors and prolonged survival of NSCLC mice. Therefore, TET effectively eliminates NSCLC cells and enhances immunotherapy efficacy through the activation of the STING pathway, and combining TET with anti-PD-1 immunotherapy deserves further exploration for applications.

AbstractThe saddleback silver-biddy Gerres limbatus (Cuvier 1830) is distributed in Indo-West Pacific Oceans and associated with shallow coastal marine waters and estuaries. In this study, the complete mitochondrial genome of G. limbatus was firstly documented, which is 16,730 bp in length, including 13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. The overall base composition of the mitochondrial genome is 26.42% A, 28.68% C, 27.32% T, and 17.58% G. The Maximum Likelihood phylogenetic tree was constructed based on COI gene of the 31 species from the family Gerreidae, with Heteroclinus puellarum and Hypopterus macropterus as outgroups. It revealed that G. erythrourus was placed as the sister group to G. limbatus.

Abstract Taking advantage of the high specific surface area of the nanoparticles, boron nitride (BN) nanoparticles were incorporated into the semi-solidified aluminium-copper alloy Al–5Cu–Mn (ZL201) system during the casting process, and its properties and enhancement mechanism were studied. The results shown that the BN in the new composite material is more uniformly distributed in the second phase (Al2Cu), which can promote grain refinement and enhance the bonding with the aluminium-based interface, and the formation of stable phases such as AlB2, AlN, CuN, etc. makes the tensile strength and hardness of the material to be significantly improved (8.5%, 10.2%, respectively). The mechanism of the action of BN in Al2Cu was analyzed by establishing an atomic model and after calculation: BN can undergo strong adsorption on the surface of Al2Cu (0 0 1), and the adsorption energy is lower at the bridge sites on the two cut-off surfaces, which makes the binding of BN to the aluminum base more stable. The charge transfer between B, N and each atom of the matrix can promote the formation of strong covalent bonds Al–N, Cu–N and Al–B bonds, which can increase the dislocation density and hinder the grain boundary slip within the alloy.

Abstract Hierarchical compartmentalization, a hallmark of both primitive and modern cells, enables the concentration and isolation of biomolecules, and facilitates spatial organization of biochemical reactions. Coacervate-based compartments can sequester and recruit a large variety of molecules, making it an attractive protocell model. In this work, we report the spontaneous formation of core-shell cell-sized coacervate-based compartments driven by spontaneous evaporation of a sessile droplet on a thin-oil-coated substrate. Our analysis reveals that such far-from-equilibrium architectures arise from multiple, coupled segregative and associative liquid-liquid phase separation, and are stabilized by stagnation points within the evaporating droplet. The formation of stagnation points results from convective capillary flows induced by the maximum evaporation rate at the liquid-liquid-air contact line. This work provides valuable insights into the spontaneous formation and maintenance of hierarchical compartments under non-equilibrium conditions, offering a glimpse into the real-life scenario.

Abstract Objective This study aims to translate the Pectus Excavatum Evaluation Questionnaire(PEEQ) into Chinese, and to comprehensively assess subjective outcomes in quality of life of children with pectus excavatum. Methods The PEEQ was translated from English to Chinese as according to the PRO translation guidelines. Structural validity and reliability of the questionnaire were examined by validated factor analysis and Cronbach’s alpha coefficient analysis respectively. Results The results of the validation factor analysis for the Chinese PEEQ parent’s and child’s questionnaires demonstrated that the fit indicators for each dimension met the required criteria. The overall Cronbach’s alpha coefficient of parent’s and child’s questionnaires were 0.840 and 0.854. Both the item-level content validity index (I-CVI) and scale-level content validity index (S-CVI) of each sub-questionnaire were 1. Conclusion The Chinese version of the PEEQ parent’s questionnaire is suitable as a proxy assessment for patients with PE, but the child’s questionnaire needs further adjustments.

Nucleic acids play a decisive role in vital life processes, such as growth, heredity, and evolution, and exploring different types of nucleic acid detection techniques has always been a research hotspot worldwide. Compared to traditional nucleic acid analysis methods, surface-enhanced Raman spectroscopy (SERS) detection has advantages, such as high sensitivity, good specificity, narrow spectral bands, minimal sample requirement, simple operation, and resistance to interference from autofluorescence and water in biological samples. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system has gained widespread attention in the fields of gene editing and biosensors. Combining the sequence-specific recognition capability of the CRISPR/Cas system with the high sensitivity fingerprinting properties of SERS technology offers a simple, rapid, and sensitive method towards nucleic acid detection. Here, common SERS Nanotags methods for nucleic acid detection are introduced, including “sandwich assay”, “signal switch assay” and HCR signal amplification. Then, the building mechanism of CRISPR-associated SERS detection is summarized. CRISPR/Cas12a activated by crRNA can recognize and lock the complementary target double-stranded DNA (dsDNA), followed by cis-cleavage of the dsDNA and trans-cleavage of the adjacent linker ssDNA. The loss of SERS signal based on aggregation is finally used for highly sensitive detection of the target DNA. Lastly, some typical applications through the integration of CRISPR/Cas and SERS technology are introduced, such as HIV-1 dsDNA, HBV DNA and AFB1 etc.

Background Polypoidal choroidal vasculopathy (PCV) is a hemorrhagic fundus disease that can lead to permanent vision loss. Predicting the treatment response to anti-VEGF monotherapy in PCV is consistently challenging. We aimed to conduct a prospective multicenter study to explore and identify the imaging biomarkers for predicting the anti-VEGF treatment response in PCV patients, establish predictive model, and undergo multicenter validation.Methods This prospective multicenter study utilized clinical characteristics and images of treatment naïve PCV patients from 15 ophthalmic centers nationwide to screen biomarkers, develop model, and validate its performance. Patients from Peking Union Medical College Hospital were randomly divided into a training set and an internal validation set. A nomogram was established by univariate, LASSO regression, and multivariate regression analysis. Patients from the other 14 centers served as an external test set. Area under the curve (AUC), sensitivity, specificity, and accuracy were calculated. Decision curve analysis (DCA) and clinical impact curve (CIC) were utilized to evaluate the practical utility in clinical decision-making.Findings The eye distribution for the training set, internal validation set, and external test set were 66, 31, and 71, respectively. The ‘Good responder’ exhibited a thinner subfoveal choroidal thickness (SFCT) (230.67 ± 61.96 vs. 314.42 ± 88.00 μm, p

Sex reversal and sex ratio bias are common in mollusks, and temperature is one of the most important environmental factors influencing gonadal development and differentiation. Here, we obtained the full-lengh cDNAs of Hsdmrt1 and Hsfoxl2 and found that they were predominantly expressed in the gonads. Furthermore, Hsdmrt1 and Hsfoxl2 showed a sexually dimorphic expression pattern, with Hsdmrt1 biased toward males and Hsfolx2 favoring females. The expression of Hsfoxl2 was inhibited by Hsdmrt1. The sex ratios of 1–3-year-old mussels H. schlegelii were assessed, and the sex ratio bias was from male to female, accompanied by a significant decrease in log10 (Hsdmrt1/Hsfoxl2). And log10(Hsdmrt1/Hsfoxl2) value outside the interval [-2,1] was considered a stable sexual state. The sex reversal in H. schlegelii was reproduced by simulating temperatures, in which male mussels at 27 °C underwent sex reversal to become females; females at 19°C underwent sex reversal to males, and the log10(Hsdmrt1/Hsfoxl2) value was altered to be in the [-2,1] interval. These results support the hypothesis that an imbalance in the expression of either gene leads to a sex reversal and that this may be regulated by temperature. This study deepens our understanding of the mechanisms of sex reversal and gonadal development in bivalves.

IntroductionThe outbreak of the Coronavirus Disease 2019 pandemic has presented significant difficulties for healthcare workers worldwide, resulting in a higher tendency to quit their jobs. This study aims to investigate the correlation between organizational support, work-family-self balance, job satisfaction, and turnover intention of healthcare professionals in China’s public hospitals.MethodsA cross-sectional survey was conducted on 5,434 health workers recruited from 15 public hospitals in Foshan municipality in China’s Guangdong province. The survey was measured by organizational support, work-family-self balance, job satisfaction, and turnover intention using a five-point Likert scale. The association between organizational support, work-family-self balance, job satisfaction, and turnover intention was investigated using Pearson correlation analysis and mediation analysis through the PROCESS macro (Model 6).ResultsOrganizational support indirectly affected turnover intention through three pathways: the mediating role of work-family-self balance, job satisfaction, and the chain mediating role of both work-family-self balance and job satisfaction.ConclusionHealth administrators and relevant government sectors should provide sufficient organizational support, enhance work-family-self balance and job satisfaction among healthcare workers, and consequently reduce their turnover intentions.

Natural bioactive compounds and plant constituents are considered to have a positive anti-inflammatory effect. This study aimed to establish a screening technique for anti-inflammatory function in foods based on label-free Raman imaging. A visible anti-inflammatory analysis method based on coherent anti-Stokes Raman scattering (CARS) was established with an LPS-induced RAW264.7 cell model. Dynamic changes in proteins and lipids were determined at laser pump light wavelengths of 2956 cm−1 and 2856 cm−1, respectively. The method was applied to a plant-based formula (JC) with anti-inflammatory activity. Q-TOF-MS and HPLC analyses revealed the main active constituents of JC as quercetin, kaempferol, l-glutamine, and sodium copper chlorophyllin. In in vitro and in vivo verification experiments, JC showed significant anti-inflammatory activity by regulating the TLR4/NF-κB pathway. In conclusion, this study successfully established a label-free and visible method for screening anti-inflammatory constituents in plant-based food products, which will facilitate the evaluation of functional foods.

Purpose: The study investigates the value of the BRAFV600E mutation in determining the aggressiveness of papillary thyroid cancer (PTC) and its correlation with ultrasound features. Methods: The study selected 176 patients with BRAFV600E mutation and 80 without the mutation who underwent surgery at Guangxi Medical University Cancer Hospital. Clinical and pathological data were collected, focusing on BRAFV600E mutations and associated ultrasonic features. Correlation analysis, as well as univariate and multivariate logistic regression analysis, were conducted to identify independent risk factors for BRAFV600E mutation. The results were verified using a nomogram model. Results: The analysis results indicate that the BRAFV600E mutation correlates with tumor size, nodule size, taller-than-wide shape, margin, and shape of papillary thyroid cancer. The receiver operating characteristic curve was used to analyze the diagnostic effect of these features on BRAFV600E mutation. The results showed that nodule size had the most significant area under the curve (AUC = 0.665). Univariate and multivariate logistic regression analyses revealed that taller-than-wide shape ≥1, ill-defined margin, irregular shape, nodule size (≤1.40 cm), TT4 (>98.67 nmol/L), and FT3 (

Current differential protection (CDP) typically requires a reliable communications to implement the correct actions. Power-line communication (PLC) thanks to its natural advantage becomes the most preferred communication medium for the CDP service; however, it always undergoes to the deep multipath fading and the strong additive noises, which impede its deployment in the CDP. In this paper, we delicate to the performance improvement of CDP service by designing a reliable and robust PLC signal in the PLC transceiver. Firstly, a quadrature amplitude modulation (QAM) based OFDM signal employing frequency-hopping (FH) technique is proposed into the classic PLC, which can boost the capability of suppressing the noise and fading in PLC channel. On the basis of the multipath fading following Manfred-Klaus model, and additive noises (background noise and impulsive noise) following Bernoulli-Gaussian model, respectively, the impact of the proposed FH/OFDM PLC signal on the protection action performance is studied via the step-by-step analysis. Finally, based on the signal derivation, the mal-operation rate and refusal operation rate of CDP are evaluated by extensive simulations. The analysis and simulations reveal that the proposed CDP system can attain the superior correct actions (e.g., lower mal-operation rate and refusal operation rate), which are benefited from the reliability and robustness of the proposed FH/OFDM PLC signal, compared to the previous CDP employing classic OFDM PLC scheme.

In order to expand the application range of casting aluminum alloy ZL105, the stirring fusion casting method was used to add carbon nanotubes (CNTs) with different content and aspect ratio into the ZL105 aluminum matrix. And then the effect of the reinforcement on the mechanical properties of the alloy was compared and analyzed. The research results show that the tensile strength and hardness of the carbon nanotube composites with different contents will be improved, but to a certain extent the elongation of the composite material will be reduced, and there is an optimal addition amount. The mechanical properties of composite materials prepared by adding CNTs with relatively small length and diameter are better. There are different forms of reinforcement mechanisms for CNTs to reinforce cast aluminum alloys, and the improvement of composite material performance is the result of the combined effect of multiple strengthening methods. The research has made a meaningful exploration for the realization of carbon nanotube reinforced aluminum matrix composites under the casting method.

Carotenoids are involved in the formation of plant leaf color as well as photosystem photoprotection. This study showed that blue light significantly induced up-regulation of the total carotenoid content in the inner leaves of orange-head Chinese cabbage (OHCC). Furthermore, the transcriptomic analysis revealed that blue light treatment induced up-regulation of genes in photosynthesis (BrHY5-2, BrCOP1 and BrDET1) and the methylerythritol 4-phosphate pathways (BrGGPS, BrDXS and BrHDR) upstream of the carotenoid metabolic pathway. Carotenoid metabolomic analysis revealed that the accumulation of several orange and red carotenoids (lycopene, zeaxanthin, β-carotene, lutein, and β-cryptoxanthin) after blue light treatment contributed to the deepening of the leaf coloration, suggesting that short-term blue light treatment could be used to boost nutritional quality. The light signal gene BrHY5-2 participated in the blue light-induced transcriptional regulation of carotenoid biosynthesis in OHCC. Overexpression of BrHY5-2 in Arabidopsis significantly increased the total carotenoid content and the sensitivity to blue light. The above findings revealed new insights about blue-light-induced carotenoid synthesis and accumulation in OHCC lines. They suggested a new engineering approach to increase the nutritional value of vegetables.

Waste slag and rubber particles are commonly used to modify concrete, offering benefits such as reduced cement consumption and lower greenhouse gas emissions during cement production. In this study, these two environmentally friendly, sustainable waste materials were proposed for the preparation of mortar intended for snow-melting pavements. A series of experiments were conducted to evaluate the performance of the material and to determine whether its compressive and flexural strengths meet the requirements of pavement specifications. The mortar’s suitability for snow-melting pavements was assessed based on its thermal conductivity, impermeability, and freeze–thaw resistance. The results indicate that slag, when used in different volume fractions, can enhance the compressive and flexural strength of the mortar. Slag also provides excellent thermal conductivity, impermeability, and resistance to freeze–thaw cycles, contributing to the overall performance of snow-melting pavements. When the slag content was 20%, the performance was optimal, with the compressive strength and flexural strength reaching 58.5 MPa and 8.1 MPa, respectively. The strength loss rate under freeze–thaw cycles was 8.03%, the thermal conductivity reached 2.2895 W/(m * K), and the impermeability pressure value reached 0.5 MPa. Conversely, the addition of rubber particles was found to decrease the material’s mechanical and thermal properties. However, when used in small amounts, rubber particles improved the mortar’s impermeability and resistance to freeze–thaw cycles. When the rubber content was 5% by volume, the impermeability pressure value reached 0.5 MPa, which was 166.7% lower than that of ordinary cement mortar. Under freeze–thaw cycles, the strength loss rate of the test block with a rubber content of 25% volume fraction was 9.83% lower than that of ordinary cement mortar.

Femtosecond laser machining offers high precision and minimal thermal impact, making it a promising technique for processing hard and brittle materials like single-crystal diamonds (SCDs). In this study, the femtosecond laser machining process for SCD material was systematically optimized to improve both machining efficiency and quality. Initial single-factor experiments were conducted to explore the effects of key process parameters—laser power, scanning speed, and number of scans—on machining performance. Subsequently, response surface methodology (RSM)-based experiments designed using the Box–Behnken method were employed to comprehensively refine the process. A regression model was developed to analyze the data, and the interaction effects of the parameters were thoroughly evaluated. The validated model identified an optimal set of parameters, resulting in a significant improvement in machining performance. This research provides a comprehensive framework for optimizing femtosecond laser machining processes, offering valuable insights critical for the production of advanced lightweight components in industries such as aerospace, optical instruments, and high-performance electronics.

The Middle Permian Qixia Formation in the Shuangyushi area, northwestern Sichuan Basin, develops shoal-facies dolomite reservoirs. To pinpoint promising reservoirs in the Qixia Formation, deep thin shoal-facies dolomite reservoirs were predicted using the techniques of pre-stack Kirchhoff-Q compensation for absorption, inverse Q filtering, low-to high-frequency compensation, forward modeling, and facies-controlled seismic meme inversion. The results are obtained in six aspects. First, the dolomite reservoirs mainly exist in the middle and lower parts of the second member of Qixia Formation (Qi2 Member), which coincide with the zones shoal cores are developed. Second, the forward modeling shows that the trough energy at the top and bottom of shoal core increases with increasing shoal-core thickness, and weak peak reflections are associated in the middle of shoal core. Third, five types of seismic waveform are identified through waveform analysis of seismic facies. Type-I and Type-II waveforms correspond to promising facies (shoal core microfacies). Fourth, vertically, two packages of thin dolomite reservoirs turn up in the sedimentary cycle of intraplatform shoal in the Qi2 Member, and the lower package is superior to the upper package in dolomite thickness, scale and lateral connectivity. Fifth, in plane, significantly controlled by sedimentary facies, dolomite reservoirs laterally distribute with consistent thickness in shoal cores at topographical highs and extend toward the break. Sixth, the promising prospects are the zones with thick dolomite reservoirs and superimposition of horst–graben structural traps.

Objective: Differentially expressed genes (DEGs) in lung adenocarcinoma (LUAD) tumor stem cells were screened, and the biological characteristics of NR5A2 gene were investigated. Methods: The expression and prognosis of NR5A2 in human LUAD were predicted and analyzed through bioinformatics analysis from a human cancer database. Gene expression and clinical data of LUAD tumor and normal lung tissues were obtained from The Cancer Genome Atlas (TCGA) database, and DEGs associated with lung cancer tumor stem cells (CSCs) were screened. Univariate and multivariate Cox regression models were used to screen and establish prognostic risk prediction models. The immune function of the patients was scored according to the model, and the relative immune functions of the high- and low-risk groups were compared to determine the difference in survival prognosis between the two groups. In addition, we calculated the index of stemness based on the transcriptome of the samples using one-class linear regression (OCLR). Results: Bioinformatics analysis of a clinical cancer database showed that NR5A2 was significantly decreased in human LUAD tissues than in normal lung tissues, and the decrease in NR5A2 gene expression shortened the overall survival and progression-free survival of patients with LUAD. Conclusion: The NR5A2 gene may regulate LUAD tumor stem cells through selective splicing mutations, thereby affecting the survival and prognosis of patients with lung cancer, and the NR5A2 gene may regulate CSCs through single nucleotide polymorphism.

PurposeThis study aims to explore the prognostic factors of head and neck rhabdomyosarcoma (HNRMS) in children and adolescents and construct a simple but reliable nomogram model for estimating overall survival (OS) of patients.MethodsData of all HNRMS patients during 2004–2018 were identified from the Surveillance, Epidemiology, and End Result database. Kaplan–Meier method was performed to calculate OS stratified by subgroups and comparison between subgroups was completed by log-rank test. Univariate and multivariate Cox regressions analysis were employed for identifying independent predictors, which subsequently were used for a predictive model by R software, and the efficacy of the model was evaluated by applying receiver operating curve (ROC), calibration and decision curve analysis (DCA).ResultsA total of 446 patients were included in the study. The 1-, 3-, and 5-year OS rate of the whole cohort was 90.6%, 80.0%, and 75.5%, respectively. The results of univariate and multivariate Cox regression analysis indicated that the primary site in parameningeal region, alveolar RMS histology, M1 stage, IRS stage 4, surgery, and chemotherapy were significant prognostic factors (all P

Development of simple and reliable sensor for detecting vitamin content is of great significance for guiding human nutrition metabolism, overseeing the quality of food or drugs, and advancing the treatment of related diseases. In this work, a simple electrochemical sensor was conveniently fabricated by modification a carbon electrode with vertically-ordered mesoporous silica film (VMSF), enabling highly sensitive electrochemical detection of vitamin B2 (VB2) based on the dual enrichment of the analyte by the supporting electrode and nanochannels. The widely used glassy carbon electrode (GCE), was preactivated using simple electrochemical polarization, The resulting preactivated GCE (p-GCE) exhibited improved potential resolution ability and enhanced peak current of VB2. Stable modification of VMSF on p-GCE (VMSF/p-GCE) was achieved without introducing another binding layer. The dual enrichment effect of the supporting p-GCE and nanochannels facilitated sensitive detection of VB2, with a linear concentration ranged from 20 nM to 7 μM and from 7 μM to 20 μM. The limit of detection (LOD), determined based on a signal-to-noise ratio of three (S/N = 3), was found to be 11 nM. The modification of ultra-small nanochannels of VMSF endowed VMSF/p-GCE with excellent anti-interference and anti-fouling performance, along with high stability. The constructed sensor demonstrated the capability to achieve direct electrochemical detection of VB2 in turbid samples including milk and leachate of compound vitamin B tablet without the need for complex sample pretreatment. The fabricated electrochemical can be easily regenerated and has high reusability. The advantages of simple preparation, high detection performance, and good regeneration endow the constructed electrochemical sensor with great potential for direct detection of small molecule in complex samples.

Abstract Retinoblastoma is the most frequent intraocular malignancy in children. Little is known on the molecular basis underlying the biological and clinical behavior of this cancer. Here, using gene expression profiles, we demonstrate the existence of two major retinoblastoma subtypes that can be divided into six subgroups. Subtype 1 has higher expression of cone related genes and higher percentage of RB1 germline mutation. By contrast, subtype 2 tumors harbor more genes with ganglion/neuronal features. The dedifferentiation in subtype 2 is associated with stemness features including low immune infiltration. Gene Otology analysis demonstrates that immune response regulations and visual related pathways are the key molecular difference between subtypes. Subtype 1b has the highest risk of invasiveness across all subtypes. The recognition of these molecular subtypes shed a light on the important biological and clinical perspectives for retinoblastomas.

Phosphatase of regenerating liver 3 (PRL3) is a specific tumor antigen overexpressed in a broad range of adult cancer types. However, its physiological expression in pediatric embryonal and mesenchymal tumors and its association with clinical outcomes in children is unknown. We sought to profile the expression of PRL3 in pediatric tumors in relation to survival outcomes, expression of angiogenesis markers, and G-protein-coupled receptor (GPCR)-mitogen-activated protein kinase (MAPK) signaling targets. PRL3-zumab, a first-in-class humanized antibody, was administered in a dose escalation schedule in a first-in-child clinical trial to study toxicity, pharmacokinetics, and clinical outcomes. Among 64 pediatric tumors, PRL3 was most frequently expressed in neuroblastoma (100%), rhabdomyosarcoma and non-rhabdomyosarcoma soft tissue sarcomas (71%), and renal sarcomas (60%) but absent in paired normal tissues. PRL3 was expressed in 75% of relapsed tumors and associated with shorter median event-free survival. Microarray profiling of PRL3-positive tumors showed elevation of angiogenin, TIMP1 and TIMP2, and GPCR-MAPK signaling proteins that commonly interacted with PRL3. The first use of PRL3-zumab in a pediatric patient saw no adverse events. A 28.6% reduction in maximum target lesion diameter was achieved when PRL3-zumab was administered concurrently with hypofractionated radiation. These findings support wider exploration of PRL3 expression in embryonal and mesenchymal tumors and further clinical application of PRL3-zumab in pediatric patients.

Abstract Background Chimeric antigen receptor (CAR) -T cell therapy is an efficient therapeutic strategy for specific hematologic malignancies. However, positive outcomes of this novel therapy in treating solid tumors are curtailed by the immunosuppressive tumor microenvironment (TME), wherein signaling of the checkpoint programmed death-1 (PD-1)/PD-L1 directly inhibits T-cell responses. Although checkpoint-targeted immunotherapy succeeds in increasing the number of T cells produced to control tumor growth, the desired effect is mitigated by the action of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in the TME. Previous studies have confirmed that targeting triggering-receptor-expressed on myeloid cells 2 (TREM2) on TAMs and MDSCs enhances the outcomes of anti-PD-1 immunotherapy. Methods We constructed carcinoembryonic antigen (CEA)-specific CAR-T cells for colorectal cancer (CRC)-specific antigens with an autocrine PD-1-TREM2 single-chain variable fragment (scFv) to target the PD-1/PD-L1 pathway, MDSCs and TAMs. Results We found that the PD-1-TREM2-targeting scFv inhibited the activation of the PD-1/PD-L1 pathway. In addition, these secreted scFvs blocked the binding of ligands to TREM2 receptors present on MDSCs and TAMs, reduced the proportion of MDSCs and TAMs, and enhanced T-cell effector function, thereby mitigating immune resistance in the TME. PD-1-TREM2 scFv-secreting CAR-T cells resulted in highly effective elimination of tumors compared to that achieved with PD-1 scFv-secreting CAR-T therapy in a subcutaneous CRC mouse model. Moreover, the PD-1-TREM2 scFv secreted by CAR-T cells remained localized within tumors and exhibited an extended half-life. Conclusions Together, these results indicate that PD-1-TREM2 scFv-secreting CAR-T cells have strong potential as an effective therapy for CRC.

Botryosphaeria dothidea, a notorious plant pathogen, is responsible for causing chestnut rot during postharvest storage. This research aimed to assess the antifungal properties of perilla essential oil (PEO) and perillaldehyde (PAE) against B. dothidea. PEO’s and PAE’s inhibitory effects on B. dothidea were investigated using an agar dilution method, a fumigation method, and an in vivo assay in chestnuts and shell buckets. Based on the results of gas chromatography-mass spectrometry, it was confirmed that the main component of PEO was elemicin. The antifungal mechanism of PEO and PAE against B. dothidea was investigated by conducting staining experiments of the fungal cell wall and cell membrane. PEO and PAE strongly inhibit the mycelial growth of B. dothidea in a dose-dependent manner. The inhibitory mechanism is mainly related to the destruction of the integrity of the fungal cell wall and plasma membrane. Notably, PEO retains its antifungal efficacy against B. dothidea in chestnuts, effectively prolonging their storage life. These findings indicate that PEO and PAE are nontoxic, eco-friendly botanical fungicides, holding promise for controlling postharvest chestnut rot.

Mitochondrial dysfunction has been increasingly recognized as a trigger for systemic lupus erythematosus (SLE). Recent bioinformatics studies have suggested Fam210b as a significant candidate for the classification and therapeutic targeting of SLE. To experimentally prove the role of Fam210b in SLE, we constructed Fam210b knockout (Fam210b−/−) mice using the CRISPR-Cas9 method. We found that approximately 15.68% of Fam210b−/− mice spontaneously developed lupus-like autoimmunity, which was characterized by skin ulcerations, splenomegaly, and an increase in anti-double-stranded DNA (anti-dsDNA) IgG antibodies and anti-nuclear antibodies(ANA). Single-cell sequencing showed that Fam210b was mainly expressed in erythroid cells. Critically, the knockout of Fam210b resulted in abnormal erythrocyte differentiation and development in the spleens of mice. Concurrently, the spleens exhibited an increased number of CD71+ erythroid cells, along with elevated levels of reactive oxygen species (ROS) in the erythrocytes. The co-culture of CD71+ erythroid cells and lymphocytes resulted in lymphocyte activation and promoted dsDNA and IgG production. In summary, Fam210b knockout leads to a low probability of lupus-like symptoms in mice through the overproduction of ROS in CD71+ erythroid cells. Thus, Fam210b reduction may serve as a novel key marker that triggers the development of SLE.

Microglia-mediated inflammatory response is one key cause of many central nervous system diseases, like Alzheimer’s disease. We hypothesized that a novel C15orf39 (MAPK1 substrate) plays a critical role in the microglial inflammatory response. To confirm this hypothesis, we used lipopolysaccharide (LPS)-and interferon-gamma (IFN-γ)-induced human microglia HMC3 cells as a representative indicator of the microglial in vitro inflammatory response. We found that C15orf39 was down-regulated when interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) expression increased in LPS/IFN-γ-stimulated HMC3 cells. Once C15orf39 was overexpressed, IL-6 and TNFα expression were reduced in LPS/IFN-γ-stimulated HMC3 cells. In contrast, C15orf39 knockdown promoted IL-6 and TNFα expression in LPS/IFN-γ-stimulated HMC3 cells. These results suggest that C15orf39 is a suppressive factor in the microglial inflammatory response. Mechanistically, C15orf39 interacts with the cytoplasmic protein arginine methyltransferase 2 (PRMT2). Thus, we termed C15orf39 a PRMT2 interaction protein (PRMT2 IP). Furthermore, the interaction of C15orf39 and PRMT2 suppressed the activation of NF-κB signaling via the PRMT2-IκBα signaling axis, which then led to a reduction in transcription of the inflammatory factors IL6 and TNF-α. Under inflammatory conditions, NF-κBp65 was found to be activated and to suppress C15orf39 promoter activation, after which it canceled the suppressive effect of the C15orf39-PRMT2-IκBα signaling axis on IL-6 and TNFα transcriptional expression. In conclusion, our findings demonstrate that in a steady condition, the interaction of C15orf39 and PRMT2 stabilizes IκBα to inhibit IL-6 and TNFα expression by suppressing NF-κB signaling, which reversely suppresses C15orf39 transcription to enhance IL-6 and TNFα expression in the microglial inflammatory condition. Our study provides a clue as to the role of C15orf39 in microglia-mediated inflammation, suggesting the potential therapeutic efficacy of C15orf39 in some central nervous system diseases.

Aliphatic glucosinolates are an abundant group of plant secondary metabolites in Brassica vegetables, with some of their degradation products demonstrating significant anti-cancer effects. The transcription factors MYB28 and MYB29 play key roles in the transcriptional regulation of aliphatic glucosinolates biosynthesis, but little is known about whether BoMYB28 and BoMYB29 are also modulated by upstream regulators or how, nor their gene regulatory networks. In this study, we first explored the hierarchical transcriptional regulatory networks of MYB28 and MYB29 in a model plant, then systemically screened the regulators of the three BoMYB28 homologs in cabbage using a yeast one-hybrid. Furthermore, we selected a novel RNA binding protein, BoRHON1, to functionally validate its roles in modulating aliphatic glucosinolates biosynthesis. Importantly, BoRHON1 induced the accumulation of all detectable aliphatic and indolic glucosinolates, and the net photosynthetic rates of BoRHON1 overexpression lines were significantly increased. Interestingly, the growth and biomass of these overexpression lines of BoRHON1 remained the same as those of the control plants. BoRHON1 was shown to be a novel, potent, positive regulator of glucosinolates biosynthesis, as well as a novel regulator of normal plant growth and development, while significantly increasing plants’ defense costs.

To further improve the mechanical properties of carbon nanotubes (CNTs) modified aluminum alloy (ZL105), the first principle was used to build the atomic structure of the alloy system and the alloy system was simulated by the VASP. After that, the heat treatment process of the cast aluminium alloy material with CNTs to enhance the alloy performance by the orthogonal experiment. The results of the research show that: (1) The energy status of the alloy system could be changed by adding the C atoms, but it did not affect the formation and structural stability of the alloy system, and the strong bond compounds formed by C atoms with other elements inside the solid solution structure can significantly affect the material properties. (2) The time of solid solution has the greatest influence on the performance of material that was modified by CNTs. The solution temperature and aging temperature were lower strength affection, and the aging time is the lowest affection. This paper provides a new research method of combining the atomic simulation with the casting experiment, which can provide the theoretical calculations to reduce the experiment times for the casting materials’ performance improvement.

BackgroundPrevious research has posited a potential correlation between the gut microbiota and the onset of appendicitis; however, the precise causal connection between appendicitis and the gut microbiota remains an unresolved and contentious issue.MethodsIn this investigation, we performed a Mendelian randomization (MR) analysis employing publicly accessible summary data extracted from genome-wide association studies (GWAS) to elucidate the potential causal nexus between the gut microbiota and the development of appendicitis. We initially identified instrumental variables (IVs) through a comprehensive array of screening methodologies, subsequently executing MR analyses using the Inverse Variance Weighted (IVW) technique as our primary approach, supplemented by several alternative methods such as MR Egger, weighted median, simple mode, and weighted mode. Additionally, we implemented a series of sensitivity analysis procedures, encompassing Cochran’s Q test, MR-Egger intercept test, Mendelian Randomized Polymorphism Residual and Outlier (MR-PRESSO) test, and a leave-one-out test, to affirm the robustness and validity of our findings.ResultsOur investigation indicates that an elevated prevalence of Deltaproteobacteria, Christensenellaceae, Desulfovibrionaceae, Eubacterium ruminantium group, Lachnospiraceae NK4A136 group, Methanobrevibacter, Desulfovibrionales, and Euryarchaeota is inversely associated with the risk of appendicitis. Conversely, we observed a positive correlation between an increased abundance of Family XIII, Howardella, and Veillonella and the susceptibility to appendicitis. Sensitivity analyses have corroborated the robustness of these findings, and Mendelian randomization analyses provided no indications of reverse causality.ConclusionOur Mendelian randomization (MR) analysis has unveiled potential advantageous or detrimental causal associations between the gut microbiota and the occurrence of appendicitis. This study offers novel theoretical and empirical insights into the understanding of appendicitis pathogenesis, along with its implications for preventive and therapeutic strategies.

BackgroundGastroduodenal ulcers are associated with Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the causal relationship between gastroduodenal ulcers and gut microbiota, especially specific gut microbiota, remains unclear.MethodsWe conducted an analysis of published data on the gut microbiota and Gastroduodenal ulcer using genome-wide association studies (GWAS). Two-sample Mendelian randomization (MR) analysis was performed to determine the causal relationship between gut microbiota and Gastroduodenal ulcer. Sensitivity, heterogeneity, and pleiotropy analyses were conducted to confirm the accuracy of the research findings.ResultsOur study showed that the abundance of Enterobacteriaceae, Butyricicoccus, Candidatus Soleaferrea, Lachnospiraceae NC2004 group, Peptococcus, and Enterobacteriales was negatively correlated with the risk of Gastroduodenal ulcer. Conversely, the abundance of Streptococcaceae, Lachnospiraceae UCG010, Marvinbryantia, Roseburia, Streptococcus, Mollicutes RF9, and NB1n was positively correlated with the risk of Gastroduodenal ulcer. MR analysis revealed causal relationships between 13 bacterial genera and Gastroduodenal ulcer.ConclusionThis study represents a groundbreaking endeavor by furnishing preliminary evidence regarding the potentially advantageous or detrimental causal link between the gut microbiota and Gastroduodenal ulcer, employing Mendelian Randomization (MR) analysis for the first time. These discoveries have the potential to yield fresh perspectives on the prevention and therapeutic approaches concerning Gastroduodenal ulcer, with a specific focus on the modulation of the gut microbiota.

Background A recent Mendelian randomization (MR) did not support an effect of the lead interleukin-6 receptor (IL-6 R) variant on risk of pulmonary arterial hypertension (PAH). Thus, we used two sets of genetic instrumental variants (IVs) and publicly available PAH genome-wide association studies (GWAS) to reassess the genetic causal link between IL-6 signaling and PAH. Methods Six independent IL-6 signaling and 34 independent soluble IL-6 receptor (sIL-6 R) genetic IVs from recent MR reports and PAH GWAS including 162,962 European individuals were used to perform this two-sample MR study. Results We found that as IL-6 signaling genetically increased, the risk of PAH reduced using IVW (odds ratio [OR] = 0.023, 95% confidence interval [CI]: 0.0013–0.393; p = .0093) and weighted median (OR = 0.033, 95% CI: 0.0024–0.467; p = .0116). Otherwise, as sIL-6 R genetically increased, the risk of PAH increased using IVW (OR = 1.34, 95% CI: 1.16–1.56; p = .0001), weighted median (OR = 1.36, 95% CI: 1.10–1.68; p = .005), MR-Egger (OR = 1.43, 95% CI: 1.05–1.94; p = .03), and weighted mode (OR = 1.35, 95% CI for OR: 1.12–1.63; p = .0035). Conclusion Our analysis suggested the causal link between genetically increased sIL-6 R and increased risk of PAH and between genetically increased IL-6 signaling and reduced risk of PAH. Thus, higher sIL-6 R levels may be a risk factor for patients with PAH, whereas higher IL-6 signaling may be a protective factor for patients with PAH.

Abstract Background The gut microbiota of fish confers various effects on the host, including health, nutrition, metabolism, feeding behaviour, and immune response. Environment significantly impacts the community structure of fish gut microbiota. However, there is a lack of comprehensive research on the gut microbiota of bighead carp in culture systems. To demonstrate the impact of culture systems on the gut microbiome and metabolome in bighead carp and investigate a potential relationship between fish muscle quality and gut microbiota, we conducted a study using 16S ribosomal ribonucleic acid sequencing, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry techniques on bighead carp in three culture systems. Results Our study revealed significant differences in gut microbial communities and metabolic profiles among the three culture systems. We also observed conspicuous changes in muscle structure. The reservoir had higher gut microbiota diversity indices than the pond and lake. We detected significant differences in phyla and genera, such as Fusobacteria, Firmicutes, and Cyanobacteria at the phylum level, Clostridium sensu stricto 1, Macellibacteroides, Blvii28 wastewater sludge group at the genus level. Multivariate statistical models, including principal component analysis and orthogonal projections to latent structures-discriminant analysis, indicated significant differences in the metabolic profiles. Key metabolites were significantly enriched in metabolic pathways involved in "arginine biosynthesis" and "glycine, serine, and threonine metabolism". Variation partitioning analysis revealed that environmental factors, such as pH, ammonium nitrogen, and dissolved oxygen, were the primary drivers of differences in microbial communities. Conclusions Our findings demonstrate that the culture system significantly impacted the gut microbiota of bighead carp, resulting in differences in community structure, abundance, and potential metabolic functions, and altered the host's gut metabolism, especially in pathways related to amino acid metabolism. These differences were influenced substantially by environmental factors. Based on our study, we discussed the potential mechanisms by which gut microbes affect muscle quality. Overall, our study contributes to our understanding of the gut microbiota of bighead carp under different culture systems.

The combination of semisolid and hot extrusion processing was applied to refine the icosahedral quasicrystalline phase (I-phase) in an extruded Mg-1.92Zn-0.34Y(wt.%) alloy for the first time. The semisolid isothermal heat treatment transformed the micron-sized I-phase particles into nano lamellar eutectic (α-Mg + I-phase) with a lamellar spacing of ~86 nm. After subsequent hot extrusion at 250 °C, the nano lamellar eutectic phases were broken into uniformly dispersed nanoscale I-phase particles. What's more, the matrix microstructure was significantly refined with an equiaxed average grain size of 2.59 ± 0.81 µm, and an unusual texture component (most of the grains’ c-axis is parallel to the extrusion direction) was observed. The processed alloy exhibited a high tensile elongation to failure (EL) of 44 ± 2.6% with an ultimate tensile strength (UTS) of 258 ± 2.0 MPa and a tensile yield strength (TYS) of 176 ± 1.6 MPa at room temperature. The high ductility from the combined effects of the grain refinement, dispersion of nanoscale I-phase particles, and the unusual texture. The uniform dispersion of nanoscale I-phase particles could promote grain refinement by particle stimulated nucleation mechanism, and thus bring the unusual texture (where the c-axis is aligned parallel to the extrusion direction during dynamic recrystallization, which contributed to ductility).

Abstract Background Guided bone self-generation with periosteum-preserved has successfully regenerated mandibular, temporomandibular and interphalangeal joint. The aim of this study was to investigate the dynamic changes of gene expression of periosteum which was involved in the guided bone self-generation. Methods Rib defects of critical size were created in mature swine with periosteum-preserved. The periosteum was sutured into a sealed sheath that closed the bone defect. The periosteum of trauma and control sites were harvested at postoperative 9 time points, and total RNA was extracted. Microarray analysis was conducted to identify the differences in the transcriptome of different time points between two groups. Results The differentially expressed genes (DEGs) between control and trauma group were different at postoperative different time points. The dynamic changes of the number of DEGs fluctuated a lot. There were 3 volatility peaks, and we chose 3 time points of DEG number peak (1 week, 5 weeks and 6 months) to study the functions of DEGs. Oxidoreductase activity, oxidation–reduction process and mitochondrion are the most enriched terms of Go analysis. The major signaling pathways of DEGs enrichment include oxidative phosphorylation, PI3K-Akt signaling pathway, osteoclast differentiation pathway and Wnt signaling. Conclusions The oxidoreductase reaction was activated during this bone regeneration process. The oxidative phosphorylation, PI3K-Akt signaling pathway, osteoclast differentiation pathway and Wnt signaling may play important roles in the guided bone self-generation with periosteum-preserved. This study can provide a reference for how to improve the application of this concept of bone regeneration.

Abstract The shuttle effect of soluble lithium polysulfides (LiPSs) between electrodes and slow reaction kinetics lead to extreme inefficiency and poor high current cycling stability, which limits the commercial application of Li–S batteries. Herein, the multi-dimensional composite frame has been proposed as the modified separator (MCCoS/PP) of Li–S battery, which is composed of CoS2 nanoparticles on alkali-treated MXene nanosheets and carbon nanotubes. Both experiments and theoretical calculations show that bifunctional catalytic activity can be achieved on the MCCoS/PP separator. It can not only promote the liquid–solid conversion in the reduction process, but also accelerate the decomposition of insoluble Li2S in the oxidation process. In addition, LiPSs shuttle effect has been inhibited without a decrease in lithium-ion transference numbers. Simultaneously, the MCCoS/PP separator with good LiPSs adsorption capability arouses redistribution and fixing of active substances, which is also beneficial to the rate performance and cycling stability. The Li–S batteries with the MCCoS/PP separator have a specific capacity of 368.6 mAh g−1 at 20C, and the capacity decay per cycle is only 0.033% in 1000 cycles at 7C. Also, high area capacity (6.34 mAh cm−2) with a high sulfur loading (7.7 mg cm−2) and a low electrolyte/sulfur ratio (7.5 μL mg−1) is achieved.

BackgroundInterstitial lung diseases (ILDs) are indispensable components of chronic respiratory diseases and global health challenges. We aimed to explore the global long-term changes in the prevalence, mortality, and disability-adjusted life years (DALYs) of ILDs; investigate the independent effect of age, period, and cohort; and project the disease burden over the next decade.MethodsData were retrieved from the Global Burden of Disease (GBD) database 2019. The joinpoint regression model was used to calculate the average annual percent change (AAPC). An age–period–cohort (APC) analysis was employed to measure the independent effect of age, period, and cohort. The Bayesian age–period–cohort (BAPC) model was used to project the global epidemiological trends until 2030.ResultsFrom 1990 to 2019, the age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life years (DALYs) rate (ASDR) of interstitial lung disease and pulmonary sarcoidosis (ILD) slightly increased from 52.66 per 100,000 [95% uncertainty interval (UI) 44.49 to 61.07] to 57.62 per 100,000 (95% UI 49.42 to 65.67), from 1.76 per 100,000 (95% UI 1.41 to 2.22) to 2.17 per 100,000 (95% UI 1.5 to 2.62), and from 41.57 per 100,000 (95% UI 33.93 to 51.92) to 46.45 per 100,000 (95% UI 35.12 to 54.98), whereas the ASPR, ASMR, and ASDR of pneumoconiosis decreased. High social-demographic index (SDI) regions possessed the highest ASPR, whereas low-middle SDI regions had the highest ASMR and ASDR, followed by low-SDI regions in ILD. Middle-SDI regions reported the highest ASPR, ASMR, and ASDR in pneumoconiosis. The age effect showed that the rate ratio (RR) was high in older adults. Period effect indicated that the RR of prevalence increased over time, whereas the RR of mortality and DALYs decreased in men but increased in women. The cohort effect exhibited that the more recent birth cohort had a higher RR than the previous cohort in prevalence. We projected that ASPR, ASMR, and ASDR would stabilize with little variation over the next decade.ConclusionThe global burden of ILDs remains relatively severe, especially among older adults, in low- and middle-SDI regions. Effective measurements are expected to improve this situation.

PurposeThis meta-analysis was exerted in assessing the anticancer efficacy and safety of nab-paclitaxel (nab-P) when combined with platinum compound agents for therapy in patients with non-small cell lung cancer (NSCLC).MethodWe systematically searched the following seven electronic databases: PubMed, Cochrane Library, Web of Science, Embase, CNKI, Wan Fang, and China Science and Technology Journal Data. Randomized comparative clinical [randomized controlled clinical trial (RCT)] studies on nab-P plus platinum and carboplatin or cisplatin in combination with conventional chemotherapy agents or traditional paclitaxel were searched.ResultsA total of 19 RCT studies involving 6,011 patients were analyzed. The primary outcome includes the overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). The secondary outcome includes adverse events (AEs). Nab-P combined with platinum (carboplatin/cisplatin) had a better ORR [odds ratio (OR) = 1.66, 95% confidence interval (CI) (1.34, 2.05), p < 0.001] and improved PFS [hazard ratio (HR) = 0.84, 95% CI: (0.74, 0.94), p = 0.01] and OS [HR = 0.86, 95% CI: (0.78, 0.96), p = 0.008] in NSCLC patients. ORR [OR = 2.18, 95% CI: (1.07, 4.43)], PFS [HR = 0.62, 95% CI: (0.40, 0.97)], and OS [HR = 0.63, 95% CI: (0.49, 0.81)] were significantly improved among patients aged >70 years, and ORR [OR = 1.80, 95% CI: (1.20, 2.70)] and PFS [HR = 0.74, 95% CI: (0.56, 0.97)] were significantly elevated with SCC rate ≥65% in NSCLC patients (all p > 0.05). Among the adverse effects, the prevalence of neutropenia, neuralgia, and arthralgia/myalgia (≥ grade 3) compared to that of the control group. On the other hand, the prevalence of anemia and thrombocytopenia was higher in the nab-P plus platinum (carboplatin/cisplatin) compared to that of controls. It is worth noting that fatigue did not show statistical significance.ConclusionNab-P in combination with carboplatin/cisplatin regimen improves efficacy and tolerability in patients with NSCLC.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022288499.

NUS1 is responsible for encoding of the Nogo-B receptor (NgBR), which is a subunit of cis-prenyltransferase. Over 25 variants in NUS1 have been reported, and these variants have been found to be associated with various phenotypes, such as congenital disorders of glycosylation (CDG) and developmental and epileptic encephalopathy (DEE). We report on the case of a patient who presented with language and motor retardation, epilepsy, and electroencephalogram abnormalities. Upon conducting whole-exome sequencing, we discovered a novel pathogenic variant (chr6:118024873, NM_138459.5: c.791 + 6T>G) in NUS1, which was shown to cause Exon 4 to be skipped, resulting in a loss of 56 amino acids. Our findings strongly suggest that this novel variant of NUS1 is responsible for the development of neurological disorders, including epilepsy. It is believed that the truncation of Nogo-B receptor results in the loss of cis-prenyltransferase activity, which may be the underlying cause of the disease.

Eye diseases can cause great inconvenience to people’s daily life; therefore, it is necessary to study the causes of ocular diseases and related physiological processes. Raman spectroscopic imaging (RSI) is a non-destructive, non-contact detection technique with the advantages of label-free, non-invasive and highly specific. Compared with other mature imaging technologies, RSI can provide real-time molecular information and high-resolution imaging at relatively low cost, making it very suitable for quantitative detection of biological molecules. RSI can reflect the overall situation of the sample, revealing the content distribution of the same substance in different areas of the sample. This review focuses on the recent advances in ophthalmology, with particular emphasis on the powerful use of RSI techniques, as well as its combination with other imaging techniques. Finally, we prospect the wider application and future potential of RSI approaches in ophthalmology.

Amidst the outbreak of the Corona Virus Disease 2019 (COVID-19), there has been a pivotal shift in nutritional focus towards adopting healthier lifestyles to enhance immune function. The successive resurgence of COVID-19 serves as a stark reminder that prioritizing the enhancement of our own immune systems is of paramount importance. Eggs are nutritious, productive, cost-effective, and affordable for consumption. Likewise, eggs are exclusive among the numerous ways consumers can obtain high-quality animal protein. Egg proteins and their peptide derivatives are abundant and biologically active and have significant therapeutic effects on chronic diseases induced by a variety of factors, including metabolic syndrome, making eggs an important raw material for the study of proteins and peptide-active substances. This paper reviewed methods for the isolation and purification of avian egg proteins and their derived peptides; the effects of the proteins and peptides in enhancing the body’s immunity, lowering blood pressure and expression levels of inflammatory factors; as well as the potential of the proteins and peptides in reducing the risk of chronic diseases such as osteoporosis and cardiovascular disease. This review was written with the expectation that it would provide a comprehensive understanding of the potential value of poultry egg proteins for maintaining health.

Abstract Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) play an important role in several pathogenic processes of the kidney. However, functions of lncRNAs in ischemic acute kidney injury (AKI) remain undefined. In this study, global lncRNA profiling indicated that many lncRNA transcripts were deregulated in kidney after ischemia reperfusion (IR). Among them, we identified IRAR (ischemia-reperfusion injury associated RNA) as a potential lncRNA candidate, which was mostly expressed by the tubular epithelial cells (TECs) after IR, involved in the development of AKI. GapmeR-mediated silencing and viral-based overexpression of IRAR were carried out to assess its function and contribution to IR-induced AKI. The results revealed that in vivo silencing of IRAR significantly reduced IR-induced proinflammatory cells infiltration and AKI. IRAR overexpression induced chemokine CCL2, CXCL1 and CXCL2 expression both in mRNA and protein levels in TECs, while, silencing of IRAR resulted in downregulation of these chemokines. RNA immunoprecipitation and RNA pulldown assay validated the association between IRAR and CCL2, CXCL1/2. Further examination revealed that specific ablation of CCL2 in TECs reduced macrophages infiltration and proinflammatory cytokine production, attenuated renal dysfunction in IR mice. Inhibition of CXC chemokine receptor 2 (receptor of CXCL1/2) reduced neutrofils infiltration, but had no overt effect on kidney function. To explore the mechanism of IRAR upregulation in kidney during IR, we analyzed promoter region of IRAR and predicted a potential binding site for transcription factor C/EBP β on IRAR promoter. Silencing of C/EBP β reduced IRAR expression in TECs. A dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) confirmed that IRAR was a transcriptional target of the C/EBP β. Altogether, our findings identify IRAR as a new player in the development of ischemic AKI through regulating chemokine production and immune cells infiltration, suggesting that IRAR is a potential target for prevention and/or attenuation of AKI.

Abstract Steroidal alkaloids possess the basic steroidal skeleton with a nitrogen atom in rings or side chains incorporated as an integral part of the molecule. They have demonstrated a wide range of biological activities, and some of them have even been developed as therapeutic drugs, such as abiraterone acetate (Zytiga®), a blockbuster drug, which has been used for the treatment of prostate cancer. Structurally diverse natural steroidal alkaloids present a wide spectrum of biological activities, which are attractive for natural product chemistry and medicinal chemistry communities. This review comprehensively covers the structural classification, isolation and various biological activities of 697 natural steroidal alkaloids discovered from 1926 to October 2021, with 363 references being cited.