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In the context of Industry 4.0, the most important trend in the shipbuilding industry is to efficiently manufacture intelligent and more environmentally friendly ships. This requires the shipbuilding industry to achieve technological innovations in all aspects of the ship's life cycle and accelerate the digital transformation of the industry. Thanks to the development of new-generation information technology, digital twins have received widespread attention and application in the manufacturing industry. The excellent performance of digital twins in monitoring, diagnosis and decision support also provides strong support for the digital transformation of the manufacturing industry. However, the application and development of digital twin technology are constrained when faced with the complex and discrete manufacturing processes in the shipbuilding industry. To address the constraints in the shipbuilding industry, promote the application of digital twin technology, and support the digital transformation of the shipbuilding industry, a statistical analysis of publications linked to the shipbuilding industry and digital twin using the Web of Science and the Scopus are done in this paper. The application and development of digital twin in the shipbuilding industry was systematically analyzed, the problems restricting the development of digital twin in the shipbuilding industry was summarized. Finally, the development trend of digital twin in shipbuilding industry prospects.

To study the multilevel coupled vibration of a naval gun under the foundation motion excitation of the ship, a mechanical-electrical-hydraulic coupled dynamic model of the naval gun including the follow-up systems’ influence was established. The subprogram for calculating the ship foundation motion was written by the harmonic superposition method, and the motion in the 3 and 5-scale sea waves was reconstructed, respectively. Based on the multidisciplinary simulation, the transmission characteristics of the ship’s foundation motion excitation along the naval gun and the influence of the tooth arc arrangement on the stabilization accuracy of the naval gun are analyzed. The results show that: the foundation motion excitation of the ship will aggravate the imbalance of the contact forces at the left and right trunnions of the cradle. A bilateral symmetrical arrangement scheme of the tooth arcs can reduce the contact forces’ imbalance at the trunnions and reduce the adverse influence on the stabilization accuracy of the naval gun. The relevant research provides theoretical support and technical guidance for the structural design or verification of the naval gun.

Abstract Background The utilization of ultrapure dialysate has been shown to decrease dialysate contamination and mitigate inflammatory responses. The central dialysate delivery system (CDDS) has the potential to attain a level of purity similar to ultrapure dialysate. Nevertheless, there is limited research examining the impact of CDDS on inflammation in comparison to single-patient dialysis fluid delivery system(SPDDS). This study aims to investigate the effects of CDDS utilizing ultrapure dialysate on ameliorating the microinflammatory state in hemodialysis patients. Method A retrospective cohort clinical study enrolled a total of 125 hemodialysis patients, with 58 patients from the CDDS unit and 67 patients from the SPDDS unit. Each participant was monitored for a period of 6 months, and the repeated measurement data was analyzed using a generalized linear mixed models (GLMM). Results The average age of the studty cohort was 56.22 ± 12.64 years. The GLMM analysis showed a significant time*group interaction effect on hs-CRP changes over the follow-up period (β = -1.966, FTime* CDDS group = 13.389, P

Abstract Purpose This study aimed to investigate the clinical significance of combining peripheral blood miR-21 and miR-486 with CT for the early cancer diagnosis in pulmonary nodules. Methods A total of 215 patients diagnosed with isolated pulmonary nodules with a history of smoking were selected as researchsubjects. 30 healthy volunteers with a history of smoking were recruitedas the control group.The selection of subjectswas based on the presence of isolated pulmonary nodules detected on chest CT scans. The training set consisted of 65 patients with lung nodules and 30 healthy smokers, while the verification setincluded 150 patients with lung nodules. Results Compared with the control group, the plasma expression level of miR-210 was significantly higher in the group of patients with benign pulmonary nodules (P

Abstract Background Oxidative stress may contribute to cardiac ryanodine receptor (RyR2) dysfunction in diabetic cardiomyopathy. Ginsenoside Rb1 (Rb1) is a major pharmacologically active component of ginseng to treat cardiovascular diseases. Whether Rb1 treat diabetes injured heart remains unknown. This study was to investigate the effect of Rb1 on diabetes injured cardiac muscle tissue and to further investigate its possible molecular pharmacology mechanisms. Methods Male Sprague-Dawley rats were injected streptozotocin solution for 2 weeks, followed 6 weeks Rb1 or insulin treatment. The activity of SOD, CAT, Gpx, and the levels of MDA was measured; histological and ultrastructure analyses, RyR2 activity and phosphorylated RyR2(Ser2808) protein expression analyses; and Tunel assay were performed. Results There was decreased activity of SOD, CAT, Gpx and increased levels of MDA in the diabetic group from control. Rb1 treatment increased activity of SOD, CAT, Gpx and decreased the levels of MDA as compared with diabetic rats. Neutralizing the RyR2 activity significantly decreased in diabetes from control, and increased in Rb1 treatment group from diabetic group. The expression of phosphorylation of RyR2 Ser2808 was increased in diabetic rats from control, and were attenuated with insulin and Rb1 treatment. Diabetes increased the apoptosis rate, and Rb1 treatment decreased the apoptosis rate. Rb1 and insulin ameliorated myocardial injury in diabetic rats. Conclusions These data indicate that Rb1 could be useful for mitigating oxidative damage, reduced phosphorylation of RyR2 Ser2808 and decreased the apoptosis rate of cardiomyocytes in diabetic cardiomyopathy.

Background Anaplastic lymphoma kinase (ALK) fusion events account for 3 to 7% of genetic alterations in patients with nonsmall cell lung cancer (NSCLC). This study aimed to explore the landscape of ALK fusion-positive and ALK fusion-negative in a large cohort of NSCLC patients.

Background NFE2L2 (nuclear factor erythroid-2-related factor-2) encodes a basic leucine zipper (bZIP) transcription factor and exhibits variations in various tumor types, including lung cancer. In this study, we comprehensively investigated the impact of simultaneous mutations on the survival of NFE2L2-mutant lung cancer patients within specific subgroups.

Abstract Welding process, as one of the crucial industrial technologies in ship construction, accounts for approximately 70% of the workload and costs account for approximately 40% of the total cost. The existing welding quality prediction methods have hypothetical premises and subjective factors, which cannot meet the dynamic control requirements of intelligent welding for processing quality. Aiming at the low efficiency of quality prediction problems poor timeliness and unpredictability of quality control in ship assembly-welding process, a data and model driven welding quality prediction method is proposed. Firstly, the influence factors of welding quality are analyzed and the correlation mechanism between process parameters and quality is determined. According to the analysis results, a stable and reliable data collection architecture is established. The elements of welding process monitoring are also determined based on the feature dimensionality reduction method. To improve the accuracy of welding quality prediction, the prediction model is constructed by fusing the adaptive simulated annealing, the particle swarm optimization, and the back propagation neural network algorithms. Finally, the effectiveness of the prediction method is verified through 74 sets of plate welding experiments, the prediction accuracy reaches over 90%.

A single-row pile dam is a type of rigid debris flow barrier structure. In order to reveal the mutual interaction effects between debris flow and a single-row pile dam and the distribution law of debris flow impact forces, an analysis of the correlation between debris flow density, characteristic particle size, and relative pile spacing (the ratio of pile gap size to debris flow characteristic particle diameter) and debris flow impact forces was conducted to obtain dimensionless parameters related to debris flow impact force and climbing height. These parameters were verified through flume model experiments to provide theoretical support for the engineering design of single-row pile dams. The results show that the impact force of the debris flow on the pile dam is mainly affected by the flow velocity, debris flow density, and relative pile spacing. The dimensionless parameters are introduced, and the semi-empirical expression of the impact load coefficient is established. The impact pressure coefficient of debris flow is classified into two categories, and the calculation model of impact load of a single-row pile dam is constructed. The research results can provide a theoretical basis and technical parameters for designing a single-row pile dam.

ABSTRACTApproximately two-thirds of hepatocellular carcinoma (HCC) is considered a “cold tumor” characterized by few tumor-infiltrating T cells and an abundance of immunosuppressive cells. Cilengitide, an integrin αvβ3 inhibitor, has failed in clinical trials as a potential anticancer drug. This failure implies that integrin αvβ3 may play an important role in immune cells. However, the expression and potential role of integrin αvβ3 in T cells of HCC patients remain unknown. Here, we established two HCC models and found that cilengitide had a dual effect on the HCC microenvironment by exerting both antitumor effect and immunosuppressive effect on T cells. This may partly explain the failure of cilengitide in clinical trials. In clinical specimens, HCC-infiltrating T cells exhibited deficient expression and activation of integrin β3, which was associated with poor T-cell infiltration into tumors. Additionally, integrin β3 functioned as a positive immunomodulatory molecule to facilitate T-cell infiltration and T helper 1-type immune response in vitro. Furthermore, T cells and platelet-derived microparticles (PMPs) co-culture assay revealed that PMPs adoptively transferred integrin β3 to T cells and positively regulated T cell immune response. This process was mediated by clathrin-dependent endocytosis and macropinocytosis. Our data demonstrate that integrin β3 deficiency on HCC-infiltrating T cells may be involved in shaping the immunosuppressive tumor microenvironment. PMPs transfer integrin β3 to T cells and positively regulate T cell immune response, which may provide a new insight into immune therapy of HCC.

BackgroundThe long-term impact of COVID-19 on the mental health and well-being of college students, specifically trends over time after full removal of COVID-19 restrictions, has not been well-studied.MethodsFour consecutive cross-sectional surveys were conducted in December 2022 (N = 689), March 2023 (N = 456), June 2023 (N = 300), and November 2023 (N = 601) at a university in Sichuan Province, China.ResultsThe proportion of students with COVID-19 panic decreased from 95.1 to 77.3% (p

Unilateral auditory deprivation (UAD) results in cross-modal reorganization of the auditory cortex (AC), which can impair auditory and cognitive functions and diminish the recovery effect of cochlear implantation. Moreover, the subcortical areas provide extensive ascending projections to the AC. To date, a thorough systematic study of subcortical auditory neural plasticity has not been undertaken. Therefore, this review aims to summarize the current evidence on the bidirectional remodeling of the central auditory system caused by UAD, particularly the changes in subcortical neural plasticity. Lateral changes occur in the cochlear nucleus, lateral superior olive, medial nucleus of the trapezoid body, inferior colliculus, and AC of individuals with UAD. Moreover, asymmetric neural activity becomes less prominent in the higher auditory nuclei, which may be due to cross-projection regulation of the bilateral pathway. As a result, subcortical auditory neural plasticity caused by UAD may contribute to the outcomes of cochlear implantation in patients with single-sided deafness (SSD), and the development of intervention strategies for patients with SSD is crucial. Considering that previous studies have focused predominantly on the neural plasticity of the AC, we believe that bidirectional remodeling of subcortical areas after UAD is also crucial for investigating the mechanisms of interventions.

BackgroundOseltamivir and baloxavir marboxil are the two primary oral drugs approved by the Food and Drug Administration (FDA) for treating influenza. Limited real-world evidence exists on their adverse events in children. The purpose of this study was to explore the adverse event (AE) profiles of oseltamivir and baloxavir marboxil in children based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsFAERS reports were collected and analyzed from the first quarter of 2019 to the third quarter of 2023. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed in data mining to quantify the signals of oseltamivir and baloxavir marboxil-related AEs.ResultsA total of 464 reports of AEs to oseltamivir as the “primary suspect (PS)” and 429 reports of AEs to baloxavir marboxil as the “PS” were retrieved in pediatric patients. A total of 100 oseltamivir-induced AE signals were detected in 17 system organ classes (SOCs), and 11 baloxavir marboxil-induced AE signals were detected in 6 SOCs after complying with the four algorithms simultaneously. Categorized and summarized by the number of reports of involvement in each SOC, the top 3 for oseltamivir were psychiatric disorders, gastrointestinal disorders, general disorders and site-of-administration conditions, respectively. The top 3 for baloxavir marboxil were injury, poisoning and surgical complications, general disorders and site of administration conditions, and psychiatric disorders, respectively.ConclusionOur study identifies potential new AE signals for oseltamivir and provides a broader understanding of the safety of oseltamivir and baloxavir marboxil in children.

Lycium ruthenicum Murray (LR), known as “black goji berry” or “black wolfberry”, is widely utilized in chinese herbal medicine. LR fruit showed its antioxidant and/or anti-inflammation activity in treating cardiac injury, experimental colitis, nonalcoholic fatty liver disease, fatigue, and aging. Glaucoma is the leading cause of irreversible blindness. Besides elevated intraocular pressure (IOP), oxidative stress and neuroinflammation were recognized to contribute to the pathogenesis of glaucoma. This study investigated the treatment effects of LR water extract (LRE) on retinal ganglion cells (RGCs) threatened by sustained IOP elevation in a laser-induced chronic ocular hypertension (COH) mouse model and the DBA/2J mouse strain. The antioxidation and anti-inflammation effects of LRE were further tested in the H2O2-challenged immortalized microglial (IMG) cell line in vitro. LRE oral feeding (2 g/kg) preserved the function of RGCs and promoted their survival in both models mimicking glaucoma. LRE decreased 8-hydroxyguanosine (oxidative stress marker) expression in the retina. LRE reduced the number of Iba-1+ microglia in the retina of COH mice, but not in the DBA/2J mice. At the mRNA level, LRE reversed the COH induced HO-1 and SOD-2 overexpressions in the retina of COH mice. Further in vitro study demonstrated that LRE pretreatment to IMG cells could significantly reduce H2O2 induced oxidative stress through upregulation of GPX-4, Prdx-5, HO-1, and SOD-2. Our work demonstrated that daily oral intake of LRE can be used as a preventative/treatment agent to protect RGCs under high IOP stress probably through reducing oxidative stress and inhibiting microglial activation in the retina.

IntroductionThis study was undertaken to explore the potential therapeutic effects of Tongyang Huoxue Granules (TYHX) on sinoatrial node (SAN) dysfunction, a cardiac disorder characterized by impaired impulse generation or conduction. The research question addressed whether TYHX could positively influence SAN ion channel function, specifically targeting the sodium-calcium exchanger (INCX) and L-type calcium channel (ICaL) of the SAN.MethodsSinoatrial node cells (SANCs) were isolated and cultured from neonatal Japanese big-eared white rabbits within 24 h of birth. The study encompassed five groups: Control, H/R (hypoxia/reoxygenation), H/R+100 μg/mL TYHX, H/R+200 μg/mL TYHX, and H/R+400 μg/mL TYHX. The H/R model, simulating hypoxia/reoxygenation stress, was induced within 5 days of culture. Whole-cell patch clamp technique was employed to record currents following a 3-min perfusion and stabilization period with TYHX.ResultsTYHX administration demonstrated improvements in the ignition phase of impaired SANCs. The half-maximal effective dose of TYHX, as determined by SANC beating frequency, was found to be 323.63 μg/mL. Inward current density of INCX increased in response to TYHX (200 and 400 μg/mL), while TYHX enhanced ICaL current density in H/R SANCs, with 400 μg/mL exhibiting greater efficacy. Additionally, TYHX regulated the gating mechanisms of ICaL by right-shifting the steady-state inactivation curve and accelerating recovery from inactivation. Notably, TYHX increased the activation time constant under 200 and 400 μg/mL, prolonged the fast inactivation time constant τ1 with 400 μg/mL, and extended the slow inactivation time constant τ2 with 100 and 400 μg/mL.Discussion and conclusionThe findings suggest that TYHX may hold promise as a therapeutic intervention for sinus node dysfunction, offering potential avenues for drug development aimed at safeguarding SAN function.

On July 5, 2021, a catastrophic debris flow disaster occured in Xiangjiao gully, Muli County, Sichuan Province. This study analyzed the formation conditions, eruption process and eruption characteristics of the debris flow through field investigation and characteristic parameter calculation. Based on the results of on-site inspection, this debris flow was mainly caused by the combined effects of forest fires, short-term heavy rainfall, and channel topography. It was a post-fire debris flow caused by rainfall runoff erosion. The heavy rain caused powerful flood erosion on the slope surface, eroded the channel, led to collapse and landslides on both sides of the channel, and resulted in significant damming effects, which enlarged the scale of the debris flow. The forest fire area in Xiangjiao gully reached 74.61%, and the high-intensity burned area was 57.98%. The critical rainfall intensity for this debris flow was 77.84 mm/h, and the cumulative rainfall was 141.60 mm. According to the calculation results of characteristic parameters, the density of this debris flow was in the range of 1.83 ～1.93 g/cm3, indicating it was a viscous debris flow. The flow velocity at the downstream outlet of the main channel was 7.22 m/s, and the peak flow rate was 759.08 m3/s. Combined with the results of the rainfall-runoff method and the morphology investigation method, the recurrence interval of this debris flow was estimated to be once in a hundred years. Considering the development trend of debris flow, it is believed that there is still a possibility of large-scale debris flow in the basin. Therefore, prevention and control suggestions including slope reinforcement in the upstream, regulation in the middle reach, and drainage in the downstream are proposed.

The liquefied natural gas (LNG) fuel tank in a large container ship is loaded with liquid LNG at an ultra-low temperature (-163°C), there is a significant temperature difference in the cargo hold area where the entire fuel tank is located, which will have an important impact on the steel grade design and structural safety of the cargo tank in container ship. This paper develops two heat transfer models using Computational Fluid Dynamics method (CFD method) and an analytical method to analyze the temperature distribution in a large container ship equipped with Type-B LNG fuel tank. These models incorporate the arrangement and heat transfer characteristics of LNG fuel tanks. The temperature field analysis is conducted under typical the environmental conditions specified in the Code for the Construction and Equipment of Ships Transporting Liquefied Gas in Bulk (IGC Code) and the United States Coast Guard Code (USCG Code), based on the CFD method and the analytical method, and the results of temperature field distribution are compared. Additionally, a parametric analysis of the hull temperature field is further carried out, the results show that the thermal conductivity of the insulation layer in LNG storage tanks and the types of the loaded liquid cargo have a limited impact on the final temperature field distribution in hull structure. However, the selection of steel grade in the local structure of the cargo hold, especially in the inner hull part, may lead to significant changes.

Abstract Simultaneously generating various motion modes with high strains in piezoelectric devices is highly desired for high-technology fields to achieve multi-functionalities. However, traditional approach for designing multi-degrees-of-freedom systems is to bond together several multilayer piezoelectric stacks, which generally leads to cumbersome and complicated structures. Here, we proposed a transparent piezo metasurface to achieve various types of strains in a wide frequency range. As an example, we designed a ten-unit piezo metasurface, which can produce high strains (ε 3 = 0.76%), and generate linear motions along X-, Y- and Z-axis, rotary motions around X-, Y- and Z-axis as well as coupled modes. An adaptive lens based on the proposed piezo metasurface was demonstrated. It can realize a wide range of focal length (35.82 cm ~ ∞) and effective image stabilization with relatively large displacements (5.05 μm along Y-axis) and tilt angles (44.02′ around Y-axis). This research may benefit the miniaturization and integration of multi-degrees-of-freedom systems.

Background & Aims: The function of cholinergic anti-inflammatory pathway (CAP) in acute liver failure (ALF) with inflammatory storm remains indefinite. The liver-gut axis has been proved to be crucial for liver homeostasis. Investigation about CAP regulation on liver-gut axis would enrich our understanding over cholinergic anti-inflammatory mechanism. Methods: Co-injection of lipopolysaccharide and D-galactosamine was used to establish the model of ALF. PNU-282987 was used to activate the CAP. Histological staining, real-time polymerase chain reaction, Western blotting, RNA sequencing, and flow cytometry were conducted. Liver biopsy specimens and patients’ serum from patients with liver failure were also analyzed. Results: We confirmed that activating the CAP alleviated hepatocyte destruction, accompanied by a significant decrease in hepatocyte apoptosis, pro-inflammatory cytokines, and NLRP3 inflammasome activation. Moreover, hepatic MAdCAM1 and serum MAdCAM1 levels were induced in ALF, and MAdCAM1 levels were positively correlated with the extent of liver damage and the expression of pro-inflammatory markers. Furthermore, activating the CAP mainly downregulated ectopic expression of MAdCAM1 on endothelial cells, and inhibition of NF-κB p65 nuclear translocation was partly attributed to the decreased MAdCAM1. Notably, in ALF, the aberrant hepatic expression of MAdCAM1 subsequently recruited gut-derived α4β7+ CD4+T cells to the liver, which exhibited an augmented IFN-γ-secreting and IL-17-producing phenotype. Finally, we revealed that the levels of serum and hepatic MAdCAM1 were elevated in patients with liver failure and closely correlated with clinical course. Increasing hepatic infiltration of β7+ cells were also confirmed in patients. Conclusions: Activating the CAP attenuated liver injury by inhibiting MAdCAM1/α4β7 -mediated gut-derived proinflammatory lymphocytes infiltration, which provides a potential therapeutic target for ALF.

Abstract Objectives To assess cigarette smoking’s effects on efficacy of the preferential Janus kinase (JAK) 1 inhibitor filgotinib and drug persistence in patients with rheumatoid arthritis (RA). Methods Efficacy in non-smokers, former smokers, and current smokers from phase 3 filgotinib trials was analyzed, including patients with inadequate response (IR) to methotrexate (MTX) or biologic disease-modifying antirheumatic drugs (bDMARDs) or who were MTX-naïve. Proportions achieving Disease Activity Score in 28 joints with C-reactive protein (DAS28[CRP]) ≤ 3.2 were compared using logistic regression. Retrospective claims-based switching data were reviewed. Results Week 12 (W12) DAS28(CRP) ≤ 3.2 was achieved by 50, 61, and 62% of MTX-IR non-smokers, former smokers, and current smokers taking filgotinib 200 mg (FIL200) + MTX vs. 23, 16, and 32% taking placebo + MTX (p

AbstractContext Levodopa combined with traditional Chinese medicine has a synergistic effect on Parkinson’s disease (PD). Recently, we demonstrated that Nardostachys jatamansi (D. Don) DC. [syn. Patrinia jatamansi D.Don, N. grandiflora DC.] (Valerianaceae) (NJ) can alleviate PD.Objective To explore the synergistic effect of NJ combined with levodopa against PD.Materials and methods The PD model was established by injecting rotenone. Eighty-four Sprague-Dawley rats were randomly divided into seven groups: sham, model, different doses of NJ (0.31, 0.62, or 1.24 g/kg) combined with levodopa (25 mg/kg), and levodopa alone (25 and 50 mg/kg) groups. The synergistic effect of the combination was investigated by pharmacodynamic investigation and detection of expression of nuclear factor erythro2-related factor 2 (Nrf2) and NLR family proteins containing Pyrin-related domain 3 (NLRP3) pathways.Results Compared with the model group, NJ + levodopa (1.24 g/kg + 25 mg/kg) increased the moving distance of PD rats in the open field (2395.34 ± 668.73 vs. 1501.41 ± 870.23, p

We assessed the flowering Chinese cabbage (Brassica rapa var. parachinensis), a specialty vegetable found in southern China. The sugar content of the stem tip is closely related to bolting and flowering. Sugar Will Eventually be Exported Transporters (SWEETs) are bidirectional sugar transporter proteins involved in numerous plant growth and development processes. The expression of BraSWEET12 is positively correlated with sugar content. However, it is unclear whether BraSWEET12 is involved in bolting and flowering. In this study, we identified and characterized BraSWEET12. BraSWEET12 in flowering Chinese cabbage contains 288 amino acids and is located on the cell membrane as a sucrose transporter protein. BraSWEET12 is highly expressed in the petals and stem tips of flowering Chinese cabbage and is upregulated by gibberellin and low temperatures. Overexpression of BraSWEET12 in Arabidopsis can increase sucrose content at the stem tip, upregulate the expression of AtAP1 and AtLFY, and advance the flowering time. Subsequently, our results indicate that BraSWEET12 is involved in sucrose accumulation at the stem tip of flowering Chinese cabbage and plays a crucial role in flowering regulation. These results provide a reference for elucidating the regulatory mechanisms underlying flowering Chinese cabbage bolting and flowering.

BackgroundTo investigate the knowledge, attitude, and practice (KAP) of atrial fibrillation (AF) among the general population in high-altitude areas.MethodologyA web-based cross-sectional study was conducted among the general population in high-altitude areas.ResultsA total of 786 valid questionnaires were enrolled, with a mean age of 34.75 ± 14.16 years. The mean score of knowledge, attitude and practice were 8.22 ± 6.50 (possible range: 0–10), 28.90 ± 5.63 (possible range: 8–40), 34.34 ± 6.44 (possible range: 9–45), respectively. The multivariate analysis showed that knowledge scores (OR = 1.108, 95% CI = 1.075–1.142, p

Papillary thyroid carcinoma (PTC), the predominant pathological type among thyroid malignancies, is responsible for the sharp increase in thyroid cancer. Although PTC is an indolent tumor with good prognosis, 60–70% of patients still have early cervical lymph node metastasis, typically in the central compartment. Whether there is central lymph node metastasis (CLNM) or not directly affects the formulation of preoperative surgical procedures, given that such metastases have been tied to compromised overall survival and local recurrence. However, detecting CLNM before operation can be challenging due to the limited sensitivity of preoperative approaches. Prophylactic central lymph node dissection (PCLND) in the absence of clinical evidence of CLNM poses additional surgical risks. This study aims to provide a comprehensive review of the risk factors related to CLNM in PTC patients. A key focus is on utilizing multimodal ultrasound (US) for accurate prognosis of preoperative CLNM and to highlight the distinctive role of US-based characteristics for predicting CLNM.

Abstract Background IL-33 is a multifunctional cytokine with dual functions. However, the clinicopathological and prognostic significance of IL-33 in cancer patients, especially in patients with hepatocellular carcinoma (HCC), remains controversial. Therefore, we conducted a study of 565 patients with HCC and 561 healthy controls and performed a meta-analysis to quantitatively evaluate the above problems. Methods We collected blood from 565 patients with HCC and 561 healthy controls. ELISA was used to detect the concentrations of IL-33 and ST2 in the serum, and RT‒PCR was used to detect the levels of IL-33 and ST2 mRNA. Meanwhile, we collected comprehensive literature on IL-33 and the clinical characteristics of cancer patients retrieved from the PubMed, Web of Science and CNKI databases as of December 2022. An odds ratio (OR) with a 95% confidence interval (CI) was used to estimate the impact through overall and stratified analyses. Results Compared with the healthy control group, the levels of ST2 mRNA and serum in the peripheral blood of HCC patients increased (p 0.05). In the meta-analysis section, at the tissue level, the overall analysis showed that the expression of IL-33 was positively correlated with tumor stage, histological grade, distant metastasis, and tumor size. Compared with patients with low IL-33 expression, the 3-year overall survival (OS) rate (OR = 3.467, p

Given that probiotics always have host-homologous and strain-specific effects on the hosts, lactic acid bacteria extracted and identified from porcine specimens can be potentially developed as probiotics for pig production. We aimed to identify lactic acid bacteria that are potentially probiotic, have good capacity of inhibiting pathogenic bacteria in intestine and are promising to be used as substitutes for antibiotics in pig production. Potential probiotic strains were extracted from 15 fecal specimens collected from 15 apparently healthy pigs, and were identified via 16S rDNA sequencing. The antimicrobial activity, tolerance to acid and bile salts, Caco-2 cell adhesiveness and susceptibility to antibiotics of the isolates were evaluated in vitro, and oral toxicity of the isolates were evaluated in mice. One Lactiplantibacillus plantarum (BJR2), two Lacticaseibacillus casei (HJD and TH2), one Lacticaseibacillus rhamnosus (MRS1), and two Enterococcus faecium (S-3 and S-4-H) were extracted from healthy pigs and underwent 16S rDNA sequencing identification. L. plantarum BJR2 and L. casei HJD exhibited broad-spectrum and higher antimicrobial activity against indicator enteric pathogens, including Salmonella choleraesuis CVCC 2139, Escherichia coli (O147:K89) CVCC 199, Escherichia coli (O141:K99) CVCC 223 and Escherichia coli (O139) CVCC 1496, among 6 tested strains. In addition, both L. plantarum BJR2 and L. casei HJD exhibited good tolerance to low pH (pH 2.5 and pH 3.5) and 0.30% bile salts, had relatively strong Caco-2 adhesiveness and carried no transferable resistant genes against antibiotics encoded by plasmid. In safety trials, these two isolates had no α or β-hemolysis activity, and were proved safe through oral toxicity tests in mice. It is concluded that L. plantarum BJR2 and L. casei HJD are potential probiotic candidate strains and their probiotic effects need to be further studied in pigs.

Abstract Diatom is a common single‐cell microalgae with large species and huge biomass. Diatom biosilica (DB), the shell of diatom, is a natural inorganic material with a micro‐nanoporous structure. Its unique hierarchical porous structure gives it great application potential in drug delivery, hemostat materials, and biosensors, etc. However, the structural diversity of DB determines its different biological functions. Screening hundreds of thousands of diatom species for structural features of DB that meet application requirements is like looking for a needle in a seaway. And the chemical modification methods lack effective means to control the micro‐nanoporous structure of DB. The formation of DB is a typical biomineralization process, and its structural characteristics are affected by external environmental conditions, genes, and other factors. This allows to manipulate the micro‐nanostructure of DB through biological regulation method, thereby transforming the screening mode of the structure function of DB from a needle in a seaway to biofabrication mode. This review focuses on the formation, biological modification, functional activity of DB structure, and its application in biomaterials field, providing regulatory strategies and research idea of DB from the perspective of biofabrication. It will also maximize the possibility of using DB as biological materials.

The FASER experiment at the LHC is designed to search for light, weakly-interacting particles produced in proton-proton collisions at the ATLAS interaction point that travel in the far-forward direction. The first results from a search for dark photons decaying to an electron-positron pair, using a dataset corresponding to an integrated luminosity of 27.0 fb−1 collected at centre-of-mass energy s=13.6 TeV in 2022 in LHC Run 3, are presented. No events are seen in an almost background-free analysis, yielding world-leading constraints on dark photons with couplings ϵ∼2×10−5−1×10−4 and masses ∼17 MeV−70 MeV. The analysis is also used to probe the parameter space of a massive gauge boson from a U(1)B−L model, with couplings gB−L∼5×10−6−2×10−5 and masses ∼15 MeV−40 MeV excluded for the first time.

Abstract Background Vogt‒Koyanagi‒Harada (VKH) disease is a multifactorial systemic autoimmune disorder against melanocytes that is characterized by panuveitis. Familial occurrence of VKH disease is rare. Here, we report two cases of a father and his son with characteristic manifestations of VKH disease. Case presentation A 53-year-old male with typical clinical symptoms of VKH disease was referred to Tangshan Eye Hospital. Examination showed the presence of ciliochoroidal effusion and exudative retinal detachment in both eyes. The patient was given intravenous methylprednisolone 120 mg for 2 days and intravenous methylprednisolone 80 mg for 1 day followed by 48 mg (1 mg/kg/day) oral methylprednisolone daily, accompanied by oral azathioprine 50 mg daily. Cycloplegic agent (0.5% tropicamide three times daily [TID]) was added. The patient was free of symptoms and recurrence within more than 1-year-follow-up period, the best corrected visual acuity (BVCA) was increased and maintained in both eyes with complete resolution of subretinal fluid. One year and nine months later, case 2 (his son) also presented with the typical clinical symptoms of VKH disease at 29 years of age. The son also recovered from VKH disease after routine and standard treatment. Conclusions To the best of our knowledge, this is the first VKH disease case report of a father-son relationship. Although genetic factors have been demonstrated to be involved in the pathogenesis of VKH disease, the different inheritance modes of VKH patients need to be further explored and studied.

Key points 1. ULD-CT qualified the requirements for diagnosis of non-displaced fractures. 2. ULD-CT for limb joint fractures is a useful alternative to digital radiography. 3. ULD-CT protocol for limb joint imaging effectively reduces the dose of radiation.

Controlling the morphology of Pt-based nanostructures can provide a great opportunity to boost their catalytic activity and durability. Here the authors report anisotropic mesoporous Pt@Pt-skin Pt3Ni core-shell framework nanowires for oxygen reduction reaction with enhanced mass activity and stability.

Abstract Plant-derived nanovesicles (PDNVs) have been proposed as a major mechanism for the inter-kingdom interaction and communication, but the effector components enclosed in the vesicles and the mechanisms involved are largely unknown. The plant Artemisia annua is known as an anti-malaria agent that also exhibits a wide range of biological activities including the immunoregulatory and anti-tumor properties with the mechanisms to be further addressed. Here, we isolated and purified the exosome-like particles from A. annua, which were characterized by nano-scaled and membrane-bound shape and hence termed artemisia-derived nanovesicles (ADNVs). Remarkably, the vesicles demonstrated to inhibit tumor growth and boost anti-tumor immunity in a mouse model of lung cancer, primarily through remolding the tumor microenvironment and reprogramming tumor-associated macrophages (TAMs). We identified plant-derived mitochondrial DNA (mtDNA), upon internalized into TAMs via the vesicles, as a major effector molecule to induce the cGAS-STING pathway driving the shift of pro-tumor macrophages to anti-tumor phenotype. Furthermore, our data showed that administration of ADNVs greatly improved the efficacy of PD-L1 inhibitor, a prototypic immune checkpoint inhibitor, in tumor-bearing mice. Together, the present study, for the first time, to our knowledge, unravels an inter-kingdom interaction wherein the medical plant-derived mtDNA, via the nanovesicles, induces the immunostimulatory signaling in mammalian immune cells for resetting anti-tumor immunity and promoting tumor eradication. Graphical Abstract

Amidst the rapid advancements in the fields of photovoltaics and optoelectronic devices, CsPbBr3 nanosheets (NSs) have emerged as a focal point of research due to their exceptional optical and electronic properties. This work explores the application potential of CsPbBr3 NSs in photonic and catalytic domains. Utilizing an optimized hot-injection method and a ZnBr2-assisted in situ passivation strategy, we successfully synthesized CsPbBr3 NSs with controlled dimensions and optical characteristics. Comprehensive characterization revealed that the nucleation environment and thickness significantly influenced the structure and optical performance of the materials. The results indicate that the optimized synthesis method enables control over the lateral dimensions of the nanoparticles, ranging from 9.1 ± 0.06 nm to 334.5 ± 4.40 nm, facilitating the tuning of the excitation wavelength from 460 nm (blue) to 510 nm (green). Further analyses involving photoresponse and electrochemical impedance spectroscopy demonstrated the substantial potential of these NSs in applications such as photocatalysis and energy conversion.

Metal halide perovskite semiconductors have emerged as promising materials for various optoelectronic applications due to their unique crystal structure and outstanding properties. Among different forms, perovskite nanowires (NWs) offer distinct advantages, including a high aspect ratio, superior crystallinity, excellent light absorption, and carrier transport properties, as well as unique anisotropic luminescence properties. Understanding the formation mechanism and structure–property relationship of perovskite NWs is crucial for exploring their potential in optoelectronic devices. In this study, we successfully synthesized all-inorganic halide perovskite NWs with high aspect ratios and an orthorhombic crystal phase using the hot-injection method with controlled reaction conditions and surface ligands. These NWs exhibit excellent optical and electrical properties. Moreover, precise control over the halogen composition through a simple anion exchange process enables the tuning of the bandgap, leading to fluorescence emission, covering a wide range of colors across the visible spectrum. Consequently, these perovskite NWs hold great potential for efficient energy conversion and catalytic applications in photoelectrocatalysis.

Transition metal dichalcogenides (TMDs), particularly monolayer TMDs with direct bandgap properties, are key to advancing optoelectronic device technology. WSe2 stands out due to its adjustable carrier transport, making it a prime candidate for optoelectronic applications. This study explores monolayer WSe2 synthesis via H2-assisted CVD, focusing on how carrier gas flow rate affects WSe2 quality. A comprehensive characterization of monolayer WSe2 was conducted using OM (optical microscope), Raman spectroscopy, PL spectroscopy, AFM, SEM, XPS, HRTEM, and XRD. It was found that H2 incorporation and flow rate critically influence WSe2’s growth and structural integrity, with low flow rates favoring precursor concentration for product formation and high rates causing disintegration of existing structures. This research accentuates the significance of fine-tuning the carrier gas flow rate for optimizing monolayer WSe2 synthesis, offering insights for fabricating monolayer TMDs like WS2, MoSe2, and MoS2, and facilitating their broader integration into optoelectronic devices.

As a direct band gap semiconductor, perovskite has the advantages of high carrier mobility, long charge diffusion distance, high defect tolerance and low-cost solution preparation technology. Compared with traditional metal halide perovskites, which regulate energy band and luminescence by changing halogen, perovskite quantum dots (QDs) have a surface effect and quantum confinement effect. Based on the LaMer nucleation growth theory, we have synthesized CsPbBr3 QDs with high dimensional homogeneity by creating an environment rich in Br− ions based on the general thermal injection method. Moreover, the size of the quantum dots can be adjusted by simply changing the reaction temperature and the concentration of Br− ions in the system, and the blue emission of strongly confined pure CsPbBr3 perovskite is realized. Finally, optical and electrochemical tests suggested that the synthesized quantum dots have the potential to be used in the field of photocatalysis.

Objectives The goal of this study was to identify protein and transcriptional biomarkers and pathways associated with baseline disease state, the effect of filgotinib (FIL) treatment on these biomarkers, and to investigate the mechanism of action of FIL on clinical improvement in patients with active psoriatic arthritis (PsA).Methods The phase II EQUATOR (NCT03101670) trial evaluated the efficacy of FIL, a Janus kinase 1-preferential inhibitor, in patients with PsA. Peripheral protein and gene expression levels in association with clinical state at baseline and post-treatment were assessed in 121 patients using linear mixed effects models for repeated measures analyses. Mediation analysis and structural equation modelling (SEM) were performed to investigate the mechanism of action of FIL at week 4 on downstream clinical improvement at week 16.Results Baseline analyses showed that markers of inflammation were significantly associated with multiple PsA clinical metrics, except for Psoriasis Area and Severity Index (PASI), which corresponded to Th17 markers. FIL treatment resulted in sustained transcriptional inhibition of immune genes and pathways, a sustained increase in B-cell fraction and mature B-cells in circulation, and a transient effect on other cell fractions. Mediation analysis revealed that changes in B cells, systemic inflammatory cytokines and neutrophils at week 4 were associated with changes in clinical metrics at week 16. SEM suggested that FIL improved PASI through reduction of IL-23 p19 and IL-12 p40 proteins.Conclusions Our results revealed that FIL treatment rapidly downregulates inflammatory and immune pathways associated with PsA disease activity corresponding to clinical improvement in PsA.Trial registration number NCT03101670.

Abstract The development of environmentally friendly and sustainable processes for the production of high‐performance organic solar cells (OSCs) has become a critical research area. Currently, Y‐series electron acceptors are widely used in high‐performance OSCs, achieving power conversion efficiencies above 19%. However, these acceptors have large fused conjugated backbones that are well‐soluble in halogenated solvents, such as chloroform and chlorobenzene, but have poor solubility in non‐halogenated green solvents. To overcome this challenge, recent studies have focused on developing green‐processed OSCs that use non‐chlorinated and non‐aromatic solvents to dissolve bulk‐heterojunction photoactive layers based on Y‐series electron acceptors, enabling environmentally friendly fabrication. In this comprehensive review, an overview of recent progress in green‐processed OSCs based on Y‐series acceptors is provided, covering the determination of Hansen solubility parameters, the use of non‐chlorinated solvents, and the dispersion of conjugated nanoparticles in water/alcohol. It is hoped that the timely review will inspire researchers to develop new ideas and approaches in this important field, ultimately leading to the practical application of OSCs.

On July 5, 2021, debris flow disasters broke out in the seven branch ditches of Xiangjiao gully under the condition of consecutive days of rain. Due to the efficient operation of the mass prediction and disaster prevention system, 20 households with 118 casualties and 14.21 million yuan of economic losses were avoided. Huangniba gully was one of the tributaries of debris flow outbreaks, with a drainage are of 14.47 km2. The scale of the debris flow flushed out objects was 12×104 m3, and several houses were damaged. During the "3·28" forest fire in 2020, the surface vegetation in Huangniba gully was severely burned, which led to dramatic changes in its debris flow disaster-pregnant environment. In the background of few debris flow activities in Huangniba gully, debris flow disasters broke out several times in 2020 and 2021. Through field investigation, it was concluded that the contradiction between the drastically changed disaster-pregnancy environment of the debris flow and the old layout of the villages was the key reason for the serious disaster in Xiapingzi Village. The entire disaster process is as follows: after the debris flow blocked the internal ditches of the village, the outflowing mountain torrents were not able to be discharged smoothly, causing a large area of flooding, which caused doubled the losses to the village. The primary treatment measures were to build a drainage channel connecting the ditch mouth and the main river and re-plan the layout of the village, so that the debris flow can be smoothly discharged into the main river and the village buildings were kept away from the direct range of the debris flow. Finally, the successful practice of the mass people monitoring and prevention system was analyzed, and the experience was summarized for reference.

Abstract Background An increasing number of studies have shown that microRNAs play an important role in the occurrence and development of small cell lung cancer, which mainly manifest as oncogenic and tumor inhibition. Therefore, microRNAs may affect the survival of patients with small cell lung cancer. In this meta-analysis, we will evaluate the role of microRNAs in the overall survival of patients with small cell lung cancer, which may provide valuable information for the treatment of small cell lung cancer. Methods We searched the PubMed, Embase, and Web of Science online databases to determine the effect of microRNAs on the prognosis of patients with small cell lung cancer. The data and characteristics of each study were extracted, and the hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to estimate the effect. Results A total of 7 articles, involving 427 subjects and 15 studies, were included in this meta-analysis. The pooled HR of the relationship between the microRNA expression level and the overall survival rate of small cell lung cancer patients was 1.25 (95% CI: 1.06–1.47). There was a significant difference in the prognostic value of oncogenic and tumor inhibition microRNAs among patients with small cell lung cancer, with pooled HRs of 1.60 (95% CI: 1.35–1.90) and 0.42 (95% CI: 0.30–0.57), respectively. Conclusions MicroRNAs have a significant impact on the overall survival of small cell lung cancer patients, suggesting that microRNAs can be used as potential prognostic markers and may provide treatment strategies for small cell lung cancer patients. Trial registration The protocol was registered on PROSPERO website with the registration number of CRD42022334363. The relevant registration information can be obtained from the website https://www.crd.york.ac.uk/prospero/#searchadvanced .

Context Ginsenoside Rb1 (Rb1) is a biologically active component of ginseng [Panax ginseng C.A. Meyer (Araliaceae)].Objective This study determined the underlying mechanisms of Rb1 treatment that acted on diabetes-injured lungs in diabetic rats.Materials and methods Streptozotocin (STZ)-induced diabetic rat model was used. Male Sprague-Dawley (SD) rats were divided into four groups (n = 10): control, Rb1 (20 mg/kg), insulin (15 U/kg to attain the euglycaemic state) and diabetic (untreated). After treatment for six weeks, oxidative stress assay; histological and ultrastructure analyses; TNF-α, TGF-β, IL-1 and IL-6 protein expression analyses; and the detection of apoptosis were performed.Results There was decreased activity of SOD (3.53-fold), CAT (2.55-fold) and GSH (1.63-fold) and increased levels of NO (4.47-fold) and MDA (3.86-fold) in the diabetic group from control. Rb1 treatment increased SOD (2.4-fold), CAT (1.9-fold) and GSH (1.29-fold) and decreased the levels of NO (1.76-fold) and MDA (1.51-fold) as compared with diabetic rats. The expression of IL-6 (5.13-fold), IL-1α (2.35-fold), TNF-α (2.35-fold) and TGF-β (2.39-fold) was increased in diabetic rats from control. IL-6 (2.43-fold), IL-1α (2.27-fold), TNF-α (1.68-fold) and TGF-β (2.3-fold) were decreased in the Rb1 treatment group. Diabetes increased the apoptosis rate (2.23-fold vs. control), and Rb1 treatment decreased the apoptosis rate (1.73-fold vs. the diabetic rats). Rb1 and insulin ameliorated lung tissue injury.Discussion and conclusions These findings indicate that Rb1 could be useful for mitigating oxidative damage and inflammatory infiltration in the diabetic lung.

Most piezoelectric coefficients in piezoelectric ceramics are zero, resulting in many piezoelectric vibration modes cannot be excited. Here, the authors propose an orderly stacked structure to achieve all nonzero piezoelectric coefficients.

Background: Methylphenidate, atomoxetine, and Amphetamine are the three most commonly used medications approved by the United States Food and Drug Administration (FDA) for the treatment of attention deficit/hyperactivity disorder (ADHD). However, a comprehensive analysis of their safety profiles across various age groups and genders in real-world contexts has yet to be conducted. In this study, a pharmacovigilance analysis was performed using the FDA Adverse Event Reporting System (FAERS) database to examine differences in adverse events between methylphenidate, atomoxetine, and Amphetamine.Methods: From January 2014 to September 2022, FAERS reports listing “Methylphenidate,” “Dexmethylphenidate,” “Atomoxetine,” “Amphetamine,” “Lisdexamfetamine,” “Dextroamphetamine,” and “Methamphetamine” as primary suspects were analyzed after removing duplicate reports. We used the standardized Medical Dictionary for Regulatory Activities (MedDRA) query generalized search for adverse events at the preferred term level based on case reports. After filtering duplicate reports, disproportionality analysis was used to detect safety signals according to the proportional reporting ratio (PRR). In order to delve into potential safety concerns, we undertook a two-step analysis of the data. Initially, the data was segmented based on age cohorts: 0–5 years, 6–12 years, 13–18 years, and individuals aged ≥19 years. Following this, after partitioning the data into males and females within the 0–18 years age group, and similarly for those aged ≥19 years, further analysis was conducted.Results: The pharmacovigilance analysis uncovered substantial safety signals in the standardized MedDRA queries. Methylphenidate was associated with dyskinesia (PRR = 21.15), myocardial infarction (PRR = 12.32), and hypertension (PRR = 8.95) in children aged 0–5, 6–12, and 13–18 years, respectively, as well as neonatal exposures via breast milk (PRR = 14.10) in adults aged ≥19 years. Atomoxetine was linked to hostility/aggression (PRR = 15.77), taste and smell disorders (PRR = 6.75), and hostility/aggression (PRR = 6.74) in children aged 0–5, 6–12, and 13–18 years, respectively, as well as hostility/aggression (PRR = 14.00) in adults aged ≥19 years. Amphetamine was associated with psychosis and psychotic disorders (PRR = 16.78), hostility/aggression (PRR = 4.39), and Other ischaemic heart disease (PRR = 10.77) in children aged 0–5 years, 6–12 years, and 13–18 years, respectively, and hostility/aggression in adults aged ≥19 years (PRR = 9.16). Significant and noteworthy adverse event signals were also identified at the preferred term level. Specifically, methylphenidate was associated with myocardial infarction, acute myocardial infarction, coronary artery dissection, electrocardiogram QT prolonged, growth retardation, self-destructive behavior, suicidal ideation, and completed suicide. Atomoxetine was linked to electrocardiogram QT prolonged, growth retardation, and tic. Amphetamine was recorded for coronary artery dissection, suicidal ideation, and completed suicide. It was observed that male patients, including both children and adults, showed a more significant and frequent occurrence of adverse events compared to females, particularly in terms of cardiac disorders. The intensity and quantity of adverse event signals were distinctly different between the two genders, with males having a higher number of signals. All detected safety signals were confirmed using signals obtained from the disproportionality analysis.Conclusion: This pharmacovigilance analysis demonstrated significant variations in the safety profiles of methylphenidate, atomoxetine, and Amphetamine across different age groups and between different genders. Following an in-depth analysis of the FAERS database, we discerned prominent safety signals. Notably, the strength of the signals associated with coronary artery dissection induced by methylphenidate and amphetamine, as well as those related to suicide, demand particular attention. Consequently, it remains imperative to persist in monitoring these medications, assessing the associated risks, and carrying out comparative studies particularly geared towards ADHD drugs.

Summary: Background: Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP. Methods: A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398. Findings: Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were −2.1 (95% CI −2.9, −1.4; p

Background and aimSepsis is a syndromic response to infection and is associated with high mortality, thus imposing a significant global burden of disease. Although low-molecular-weight heparin (LMWH) has been recommended to prevent venous thromboembolism, its anticoagulant and anti-inflammatory effects in sepsis remain controversial. Owing to the modification of the Sepsis-3 definition and diagnostic criteria, further evaluation of the efficacy and benefit population of LMWH is required.MethodsWe performed a retrospective cohort study to assess whether LMWH improved the inflammation, coagulopathy, and clinical outcomes against Sepsis-3 and to identify the target patients. All patients diagnosed with sepsis at the First Affiliated Hospital of Xi'an Jiaotong University (the largest general hospital in northwest China) from January 2016 to December 2020 were recruited and re-evaluated using Sepsis-3 criteria.ResultsAfter 1:1 propensity score matching, 88 pairs of patients were categorized into the treatment and control groups based on subcutaneous LMWH administration. Compared with the control group, a significantly lower 28-day mortality was observed in the LMWH group (26.1 vs. 42.0%, p = 0.026) with a comparable incidence of major bleeding events (6.8 vs. 8.0%, p = 0.773). Cox regression analysis showed that LMWH administration was the independent protective factor for septic patients (aHR, 0.48; 95% CI, 0.29–0.81; p = 0.006). Correspondingly, the LMWH treatment group showed a significant improvement in inflammation and coagulopathy. Further subgroup analysis showed that LMWH therapy was associated with favorable outcomes in patients younger than 60 years and diagnosed with sepsis-induced coagulopathy (SIC), ISTH overt DIC, non-septic shock, or non-diabetics and in patients included in the moderate-risk group (APACHE II score 20–35 or SOFA score 8–12).ConclusionOur study results showed that LMWH improves 28-day mortality by improving inflammatory response and coagulopathy in patients meeting Sepsis-3 criteria. The SIC and ISTH overt DIC scoring systems can better identify septic patients who are likely to benefit more from LMWH administration.

The major histocompatibility complex (MHC) can recognize and bind to external peptides to generate effective immune responses by presenting the peptides to T cells. Therefore, understanding the binding modes of peptide–MHC complexes (pMHC) and predicting the binding affinity of pMHCs play a crucial role in the rational design of peptide vaccines. In this study, we employed molecular dynamics (MD) simulations and free energy calculations with an Alanine Scanning with Generalized Born and Interaction Entropy (ASGBIE) method to investigate the protein–peptide interaction between HLA-A*02:01 and the G9209 peptide derived from the melanoma antigen gp100. The energy contribution of individual residue was calculated using alanine scanning, and hotspots on both the MHC and the peptides were identified. Our study shows that the pMHC binding is dominated by the van der Waals interactions. Furthermore, we optimized the ASGBIE method, achieving a Pearson correlation coefficient of 0.91 between predicted and experimental binding affinity for mutated antigens. This represents a significant improvement over the conventional MM/GBSA method, which yields a Pearson correlation coefficient of 0.22. The computational protocol developed in this study can be applied to the computational screening of antigens for the MHC1 as well as other protein–peptide binding systems.

Geotechnical control engineering is widely used in the treatment of debris flow disasters, and the damage degree of the engineering will have a certain impact on the functionality of the engineering. It affects the continuous exertion of benefits. This paper selects geotechnical control engineering of 18 debris flow gullies in Wenchuan area as the research objects, combined with field investigation, the damage degree of control engineering was evaluated. The system of evaluation index is generally divided into two factors: check dam factor and drainage channel factor. The secondary evaluation indexes are refined, including the damage degree of dam foundation, the damage degree of dam abutment, the damage degree of dam body, scouring degree of foundation, structural impact degree and slope thrust degree. The fuzzy comprehensive evaluation method is used to construct the judgment matrix and membership function, and the damage degree is divided into four grades: excellent, good, medium and poor. The evaluation results show that except for Banzi gully and Dengxi gully, the damage grades of other debris flow control engineering are good or excellent, and the evaluation results are consistent with the field investigation.

Multidrug resistance (MDR) promotes tumor recurrence and metastasis and heavily reduces anticancer efficiency, which has become a primary reason for the failure of clinical chemotherapy. The mechanisms of MDR are so complex that conventional chemotherapy usually fails to achieve an ideal therapeutic effect and even accelerates the occurrence of MDR. In contrast, the combination of chemotherapy with dual-drug has significant advantages in tumor therapy. A novel dual-drug codelivery nanosystem, which combines dual-drug administration with nanotechnology, can overcome the application limitation of free drugs. Both the characteristics of nanoparticles and the synergistic effect of dual drugs contribute to circumventing various drug-resistant mechanisms in tumor cells. Therefore, developing dual-drug codelivery nanosystems with different multidrug-resistant mechanisms has an important reference value for reversing MDR and enhancing the clinical antitumor effect. In this review, the advantages, principles, and common codelivery nanocarriers in the application of dual-drug codelivery systems are summarized. The molecular mechanisms of MDR and the dual-drug codelivery nanosystems designed based on different mechanisms are mainly introduced. Meanwhile, the development prospects and challenges of codelivery nanosystems are also discussed, which provide guidelines to exploit optimized combined chemotherapy strategies in the future.