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Abstract The scarcity of suitable high-throughput screening technology for hydrogen sulfide (H2S) donors has hampered the discovery of H2S donors. In this study, a long-lived cyclometalated iridium complex was rationally designed as a mitochondria-targeted H2S probe to monitor the real-time dynamic change of H2S. By using the time-resolved emission spectroscopy (TRES) technique, an anti-interference high-throughput screening system was developed to monitor H2S in living cells with decreased false negative results. As a proof-of-concept, three natural products were identified as potential H2S donors from a natural product library using the developed TRES probe. Notably, the discovery of allicin and diallyl trisulfide demonstrated the feasibility of this screening platform, while garlic-derived allyl methyl sulfide was explored as a H2S donor candidate. The results were further validated by a commercial assay. We anticipate this high-throughput platform could facilitate the discovery of H2S donors by discriminating the endogenous interfering fluorescence from biological systems.

Abstract The efficacy and safety of venetoclax in newly diagnosed pediatric acute myeloid leukemia (AML) are not well-established as they are in adults. Children newly diagnosed with AML were recommended for induction therapy with venetoclax and chemotherapy or hypomethylating agents (HMAs) as per for the ChiCTR1900027146 trial. Venetoclax was administered at a consistent dose of 200 mg/m2/day for 28 days, with adjustments when used concurrently with azoles. The study measured both the remission rates and the safety assessments of venetoclax. We enrolled 45 newly diagnosed pediatric patients with AML. The complete remission rates were 94.7% in the low/middle-risk group and 80.8% in the high-risk group; MRD-negative rates were 52.6% and 38.5% in the low/middle-risk group and high-risk group, respectively. Venetoclax based combination therapy was well tolerated by the majority of patients. The median duration of venetoclax dosing was 18 days (range 9–28), with hematological toxicity and infection being the most common adverse events. Venetoclax-based induction regimens demonstrated a high response rate and safety profile in newly diagnosed pediatric AML cases. This underscores the significance of venetoclax as a viable treatment option for untreated AML, extending beyond its role as salvage therapy for refractory/relapsed AML.

Abstract Background To investigate the association between low transthyretin (prealbumin) concentration and mortality or readmission for all causes in elderly inpatients. Methods This analysis is based on a prospective cohort study conducted from September 2018 to April 2019 in ten wards of three tertiary referral hospitals in Beijing. Patients aged 65 years or older were enrolled, and their clinical data, laboratory test results, and auxiliary test results for patients were collected. A three-year follow-up was conducted with patients. Based on the 5th and 95th percentiles of transthyretin concentration, patients were split into three groups. The correlation between transthyretin concentration and the outcome of elderly hospitalized patients was investigated. The primary outcome of the research was death or readmission from all causes within three years. Results Among the 636 individuals in the study, 335 (52.7%) were males, with a median age of 74.7 years (interquartile range [IQR]: 69.3–80.1). During a median follow-up period of 1,099.0 days (IQR: 1,016.3-1,135.0), 363 individuals (57.0%) experienced all-cause mortality or readmission events. Patients with transthyretin concentrations at or below the 5th percentile had a significantly increased risk of all-cause mortality or readmission compared to those with concentrations between the 5th and 95th percentiles (hazard ratio [HR]: 2.25; 95% confidence interval [CI]: 1.55–3.26). Even after adjusting for potential confounders, low transthyretin concentration remained an independent risk factor for poor prognosis in elderly inpatients (HR: 1.84; 95% CI: 1.03–3.28). Since women have consistently lower baseline transthyretin levels than men, we performed gender-specific analysis. We found that low transthyretin concentration is an independent risk factor for adverse prognosis in elderly male inpatients (HR: 2.99; 95% CI: 1.35–6.62) but not in females. Conclusions Low transthyretin concentrations are associated with increased all-cause mortality or readmission in elderly inpatients, particularly among male patients. Graphical Abstract

Abstract Background Homocysteine (HCY) is a sulfur-containing amino acid that is an independent or important risk factor for the occurrence of many chronic diseases and is one of the most important indicators for determining health risks. However, existing HCY detection methods do not meet the requirements of clinical diagnosis. Therefore, there is an urgent need to establish new detection methods to meet the needs of clinical detection. Results In this study, we used the principle of competitive method to establish a new method for the determination of HCY in human serum using a chemiluminescent enzyme immunoassay in conjunction with a chemiluminescent assay instrument that uses magnetic microparticles as the solid phase of the immunoreaction. The established method achieved satisfactory results in terms of minimum detection limit, specificity, accuracy, and clinical application. The limit of detection was 0.03 ng/mL. The intra-assay coefficient of variation (CV) was 1.94–5.05%, the inter-assay CV was 2.29–6.88%, and the recovery rate was 88.60–93.27%. Cross-reactivity with L-cysteine ranged from 0.0100 to 0.0200 μmol/L, and cross-reactivity with glutathione ranged from 0.0100 to 0.200 μmol/L, all of which were less than the limit of detection (LoD) of this method. The linear factor R of this method was greater than 0.99. Conclusions In summary, the developed method showed a good correlation with the product from Abbott. A total of 996 clinical patients with cardiovascular diseases were evaluated using the method developed in this study.

Objective Distal tibial deformities can significantly impact patients if left uncorrected, often leading to pain, alterations in gait, and the eventual development of post‐traumatic arthritis. The criteria for surgical correction in these patients continues to be a subject of debate, while supramalleolar osteotomy (SMO) is an effective method for correcting distal tibial deformities. The purpose of this study was to evaluate and compare the clinical results of SMO using internal fixation or using computer‐assisted hexapod external fixator in the treatment of distal tibial deformity. Methods A retrospective study was conducted on 290 patients who underwent SMO between June 2015 and January 2023. Forty‐four patients met the inclusion and exclusion criteria. Among the participants, 19 underwent SMO combined with a computer‐assisted hexapod external fixator, while 25 received SMO with plate and screw internal fixation. The tibial anterior surface (TAS) angle, tibial lateral surface (TLS) angle, the tibiotalar (TT) angle and the talocrural (TC) angle were assessed on weight‐bearing X‐ray films. Functional assessments were performed according to the American Orthopedic Foot and Ankle Society (AOFAS) ankle‐hindfoot score. Results The study followed patients for an average duration of 31.7 ± 15.3 months, with a range from 12 to 67 months. Successful bone union was achieved in all cases. For patients treated with the computer‐assisted hexapod external fixator, significant improvements were observed: the mean deviation in sagittal plane deformity parameters decreased from 14.3 ± 10.4 degrees preoperatively to 2.8 ± 3.8 degrees postoperatively (p

Objective Surgical technique in distraction osteogenesis for the treatment of brachymetatarsia can influence the final prognosis. However, there are currently no standardized guidelines for surgical procedures and complication management. The aim of this study is to investigate the effect of bone lengthening with external fixation by minimally invasive osteotomy based on Ilizarov technique in the treatment of congenital brachymetatarsia. Methods A retrospective study was conducted on patients with congenital brachymetatarsia treated by metatarsal lengthening, from June 2017 to December 2020. There were 11 patients with 17 shorted fourth metatarsals, including 10 females and 1 male, with age of 24.6 ± 4.5 years (16–31 years). Six patients were bilaterally involved. Orthofix external fixator mini track was installed through dorsal approach and the fourth MTP joints were temporarily fixed by Kirschner wire. Bone lengthening was performed after a minimally invasive osteotomy at the proximal metatarsals. American Orthopedic Foot and Ankle Society (AOFAS) lesser metatarsophalangeal‐interphalangeal (MTP‐IP) scores, metatarsal length, complications were recorded. Statistical comparison was performed using the paired t‐student test for pre‐ and postoperative AOFAS MTP‐IP scores. Results Patients were followed up for 55 ± 10.8 months. The mean length of the fourth metatarsal bone was 49.9 ± 2.9 mm preoperatively. The mean metatarsal shortage was 18.8 ± 3.1 mm. The mean lengthening achieved was 19.8 ± 3.3 mm, with a lengthening ratio of 39.7% ± 6.6%. The lengthened callus ossified completely at 3–4 months after operation. All patients were satisfied with the results of lengthening. The AOFAS scores were improved significantly from 83.7 ± 4.2 preoperatively to 93.2 ± 2.7 postoperatively (t = −10.27, p

Cross-media operating robots are versatile machines that can move and perform tasks in various environments such as air, water, and land. These robots are highly adaptable and flexible, making them useful in a wide range of applications, including exploration, marine research, environmental monitoring, military reconnaissance, industrial and infrastructure maintenance, and emergency response. Cross-media operating robots need to switch corresponding movement modes in different environments, such as using buoys or propellers in water and wheels or legs on land. However, existing amphibious robots often have complex structures and high maintenance costs because they rely on multiple sets of actuated systems, which leads to increased difficulty in control and longer operating times. To address these challenges, this study presents a novel wave-inspired actuated ray-inspired amphibious robot (WARAR). The WARAR design includes a wave-inspired actuated mechanism that transforms motor rotation into sinusoidal waves by passing a spiral rod through movable hinges arranged side by side, resulting in better mobility and obstacle-crossing capability. Two of these mechanisms are arranged side by side, enabling WARARs to adopt the differential principle for steering control. Based on this principle, a flexible ray-inspired fin is designed to transform the actuated force of the wave-inspired mechanisms into a propulsion force for swimming in the water by connecting the supporting bone to one end of the movable hinge and covering it with flexible silicone rubber. Moreover, by utilizing the two structures, a new type of WARAR that only requires control of the wave-inspired mechanism for operation on land, in water, and during transitions between the two is designed. Furthermore, a suitable electronic control room is designed to make the electronic control system of WARAR waterproof that can also be sealed to provide buoyancy. Specifically, WARARs are mainly fabricated through three-dimensional printing, which effectively reduces weight. The simple actuated system structure and lightweight overall machine are the keys to the high flexibility of WARARs. Moreover, the kinematic models of WARARs are established, and the swimming mode hydrodynamic characteristics of WARARs are analyzed using simulation methods. Given the complex operating environments of water and land media, a trajectory planning method is proposed using the A* planning method that considers safe areas. Finally, an experimental platform is constructed with land and water environments to test the performance of WARARs during moving, climbing, turning, and swimming. The effectiveness of the proposed trajectory planning methods for crossing water and land media is verified. Overall, the development of WARARs provides a more efficient and cost-effective solution for cross-media operating robots with applications in various fields.

Abstract Glioblastoma (GBM), a primary brain tumor, exhibits remarkable invasiveness and is characterized by its intricate location, infiltrative behavior, the presence of both the blood–brain barrier (BBB) and the blood–brain tumor barrier (BBTB), phenotypic diversity, an immunosuppressive microenvironment with limited development yet rich vascularity, as well as the resistant nature of glioblastoma stem cells (GSCs) towards traditional chemotherapy and radiotherapy. These formidable factors present substantial obstacles in the quest for effective GBM treatments. Following extensive research spanning three decades, the hepatocellular receptor A2 (EphA2) receptor tyrosine kinase has emerged as a promising molecular target with translational potential in the realm of cancer therapy. Numerous compounds aimed at targeting EphA2 have undergone rigorous evaluation and clinical investigation. This article provides a comprehensive account of the distinctive roles played by canonical and non-canonical EphA2 signaling in various contexts, while also exploring the involvement of the EphA2-ephrin A1 signaling axis in GBM pathogenesis. Additionally, the review offers an overview of completed clinical trials targeting EphA2 for GBM treatment, shedding light on both the prospects and challenges associated with EphA2-directed interventions in the domain of cancer therapeutics.

Abstract Background Retroperitoneal liposarcoma (RPLPS) is a relatively rare disease. Liposarcomas vary in size, but sizeable RPLPS larger than 30 cm in diameter are very rare, and their diagnosis and treatment present significant challenges. Case presentation We report a 58-year-old male patient who was admitted to the hospital with an increased abdominal circumference and was later diagnosed with a giant RPLPS. The liposarcoma was found to adhere to the right kidney and the entire ureter, invading the ascending colon. The patient underwent complete combined surgical resection. The tumor was removed intact, measured 55.0 cm × 30.0 cm × 18.0 cm, and weighed 19.8 kg. Histopathologic analysis revealed well-differentiated liposarcoma (WDLPS). The patient was successfully discharged from the hospital and followed up for 6 months with no signs of recurrence. Conclusion RPLPS is a rare tumor with atypical clinical presentation. Surgery remains the most effective method of treatment for retroperitoneal sarcomas, with complete removal if there is local invasion. Preoperative examination, including three-dimensional (3D) reconstruction, is essential for surgical success. The role of adjuvant radiotherapy or chemotherapy remains controversial. However, clinicians should not rule them out as viable options.

Abstract Non-human primates remain the most useful and reliable pre-clinical model for many human diseases. Primate breath profiles have previously distinguished healthy animals from diseased, including non-human primates. Breath collection is relatively non-invasive, so this motivated us to define a healthy baseline breath profile that could be used in studies evaluating disease, therapies, and vaccines in non-human primates. A pilot study, which enrolled 30 healthy macaques, was conducted. Macaque breath molecules were sampled into a Tedlar bag, concentrated onto a thermal desorption tube, then desorbed and analyzed by comprehensive two-dimensional gas chromatography-time of flight mass spectrometry. These breath samples contained 2,017 features, of which 113 molecules were present in all breath samples. The core breathprint was dominated by aliphatic hydrocarbons, aromatic compounds, and carbonyl compounds. The data were internally validated with additional breath samples from a subset of 19 of these non-human primates. A critical core consisting of 23 highly abundant and invariant molecules was identified as a pragmatic breathprint set, useful for future validation studies in healthy primates.

Abstract The prognoses of patients who undergo open spinal endoscopy (OSE) decompression significantly differ by scoliosis type and symptom despite the use of uniform standards and procedures for the decompression surgery. These differences may be directly related to the selection and formulation of surgical strategies but their cause remains unclear. The aim of this study was to verify and evaluate the efficacy of the "Symptom, Stenosis and Segment classification (SSS classification)" in determining an appropriate surgical strategy and to analyze the differences in the outcomes of different patients after receiving the selected surgical strategy. The results of this study ultimately provide a theoretical basis for the specific optimization of surgical strategies guided by the "SSS classification". This work was a retrospective study. We reviewed 55 patients with scoliosis and spinal stenosis who underwent "pear-shaped" decompression under OSE from May 2021 to June 2023 treated by our surgical team. To classify different types of patients, we defined the "SSS classification" system. The permutation and combination of subtypes in Symptom (including three subtypes: Convex = v, Concave = c and Bilateral = b), Stenosis (including three subtypes: Convex = v, Concave = c and Bilateral = b), and Segment (including two subtypes: Edge = e and Inside = i) yields 18 possible types (details in Table 1) in this classification system. To classify different types of surgeries, we also defined the operation system. The VAS Back and VAS Leg scores after surgical treatment were significantly lower in all patients 3 months after surgery than before surgery. (**P

Abstract Background Viral hepatitis imposes a heavy disease burden worldwide and is also one of the most serious public health problems in China. We aimed to describe the epidemiological characteristics of hepatitis in China and to investigate the influencing factors. Methods We first used the JoinPoint model to analyze the percentage change (APC) and average annual percentage change (AAPC) of hepatitis in Chinese provinces from 2002 to 2021. We then explored the influencing factors by using the time-series global principal component analysis (GPCA) and the panel fixed-effects model. Results The disease burden varied across different provinces from 2002 to 2021. The AAPC of the total HAV incidence decreased by 10.39% (95% CI: [-12.70%, -8.02%]) from 2002 to 2021. Yet the AAPC of HBV, HCV, and HEV increased by 1.50% (95% CI: [0.23%, 2.79%]), 13.99% (95% CI: [11.28%, 16.77%]), and 7.10% (95% CI: [0.90%, 13.69%]), respectively. The hotspots of HAV, HBV, HCV, and HEV moved from the west to the center, from the northwest to the southeast, from the northeast to the whole country, and from the northeast to the southeast, respectively. Different types of viral hepatitis infections were associated with hygiene, pollutant, and meteorological factors. Their roles in spatial-temporal incidence were expressed by panel regression functions. Conclusions Viral hepatitis infection in China showed spatiotemporal heterogeneity. Interventions should be tailored to its epidemiological characteristics and determinants of viral hepatitis.

BackgroundFollowing the Chinese guidelines’ recommendation to completely cancel routine cephalosporin skin tests, the choice of cephalosporin as surgical prophylactic medication was affected. This was due to the limited cognition of the predictive value of cephalosporin skin test or the desire to avoid medical disputes. The aim of this retrospective study was to evaluate whether the pharmacist-led perioperative antibiotic prophylaxis model could improve clinicians’ medical behavior in choosing cephalosporin antibiotics for surgical prophylaxis.MethodsFrom July 2021 to May 2022, a retrospective analysis was conducted on the selection of surgical preventive medication, skin test, postoperative infection and adverse drug reactions in foot and ankle surgery. The study was divided into three period: the rountine cephalosporin skin test period (Period I: Skin Test), the period when the routine cephalosporin skin test was cancelled but the pharmacist did not intervene (Period II: Cancel Skin Test), and the period when the pharmacist-led perioperative antibiotic prophylaxis was implemented after the cancellation of the cephalosporin skin test (Period III: Pharmacist Intervention).ResultsA total of 1,583 patients were enrolled in this study. There was no significant difference in the utilization rate of cefuroxime between the routine skin test stage and the skin test cancelled stage [74.92% (Period I) vs. 74.54% (Period II), P > 0.05]. However, in the pharmacist intervention stage, the usage rate of cefuroxime significantly increased compared to the initial stage when the skin test was cancelled [87.07% (Period III) vs. 74.54% (Period II), P < 0.05]. The use of cephalosporins also increased in patients with self-reported beta-lactam allergies between these stages [41.94% (Period III) vs. 3.22% (Period II), P < 0.05)]. There was no significant difference in the incidence of postoperative infection and adverse drug reactions among the three periods.ConclusionThe pharmacist-led perioperative antibiotic prophylaxis model can significantly improve the medical behavior of clinicians in choosing cephalosporin antibiotics as surgical prophylactic medication and optimize the perioperative medication plan.

Abstract An efficient and facile water dissociation process plays a crucial role in enhancing the activity of alkaline hydrogen evolution reaction (HER). Considering the intricate influence between interfacial water and intermediates in typical catalytic systems, meticulously engineered catalysts should be developed by modulating electron configurations and optimizing surface chemical bonds. Here, a high‐entropy double perovskite (HEDP) electrocatalyst La2(Co1/6Ni1/6Mg1/6Zn1/6Na1/6Li1/6)RuO6, achieving a reduced overpotential of 40.7 mV at 10 mA cm−2 and maintaining exemplary stability over 82 h in a 1 m KOH electrolyte is reported. Advanced spectral characterization and first‐principles calculations elucidate the electron transfer from Ru to Co and Ni positions, facilitated by alkali metal‐induced super‐exchange interaction in high‐entropy crystals. This significantly optimizes hydrogen adsorption energy and lowers the water decomposition barrier. Concurrently, the super‐exchange interaction enhances orbital hybridization and narrows the bandgap, thus improving catalytic efficiency and adsorption capacity while mitigating hysteresis‐driven proton transfer. The high‐entropy framework also ensures structural stability and longevity in alkaline environments. The work provides further insights into the formation mechanisms of HEDP and offers guidelines for discovering advanced, efficient hydrogen evolution catalysts through super‐exchange interaction.

BackgroundIntrinsic capacity (IC), as a comprehensive measure of an individual’s functional ability, has gained prominence in the framework for healthy aging introduced by the World Health Organization (WHO). As internet usage continues to integrate into daily life, it is imperative to scrutinize the association between internet use and IC to effectively promote healthy aging among the middle-aged and older population. ObjectiveThis study aimed to investigate whether daily internet use in middle-aged and older adults delays or accelerates the decline in IC. MethodsParticipants included in the China Health and Retirement Longitudinal Study (CHARLS) comprised individuals aged ≥45 years residing in China. We analyzed 4 years of CHARLS data from the first wave (May 2011-March 2012) to the third wave (July 2015-January 2016). Data from the first and third waves were used for longitudinal studies. Self-reported data encompassed internet use, frequency of use, and demographic baseline characteristics. In addition, the IC evaluation involved physical examination and blood test data. Initially, linear regression was used to assess the relationship between daily internet use and IC, followed by regression splines to explore potential nonlinear associations. Subgroup and sensitivity analyses were used to investigate the heterogeneity of IC in specific conditions and the robustness of our results. Mediation effect analysis was conducted to identify the factors that mediate the relationship between daily internet use and IC, focusing on social participation, physical activity, and health status. ResultsAmong the 12,826 participants included in the longitudinal analyses, 12,305 (95.9%) did not use the internet, while 521 (4.1%) reported daily internet use with a mean age of 52.62 (SD 7.67) years. After adjusting for demographic variables, socioeconomic factors, lifestyle behaviors, and health conditions and examining the impact of daily internet use and frequency on changes in IC, our findings indicated important associations. Specifically, daily internet use is significantly linked to a slower decline in IC over time (marginal effect 1.58, 95% CI 1.03-2.12; P

Objectives: Intrinsic capacity (IC), a multidimensional construct encompassing mental and physical capacities, has been established in the aging framework by the World Health Organization. However, the detailed relationship between IC and Chinese sleep patterns (nighttime sleep and post-lunch naps) remains inadequately elucidated. Methods: Participants in this study were individuals aged ≥45 years residing in China, included in the China Health and Retirement Longitudinal Study (CHARLS). We analyzed 4 years of CHARLS data from the first wave (May 2011–March 2012) to the second wave (July 2015–January 2016). Data from these waves were utilized for longitudinal analysis. Self-reported data included nighttime sleep and nap duration, along with other baseline characteristics. The IC evaluation involved physical examinations and blood tests. Initially, linear regression was used to assess the relationship between total sleep duration, nighttime sleep duration, nap duration, and IC change between the two waves that were determined by marginal effects (ME) and their corresponding 95% confidence intervals (CIs). Regression splines were employed to explore potential nonlinear associations. Subgroup and sensitivity analyses were conducted to investigate the heterogeneity of IC change under specific conditions and the robustness of our results. Mediation analysis was performed to identify potential factors mediating the relationship between sleep patterns and IC change. Results: Both excessive (>10 h) (total, ME: −1.12; 95% CI: −1.61, −0.64; nighttime, ME: −1.44; 95% CI: −2.29, −0.59) and insufficient (

Abstract The Ili River Valley, located in the northwest of China, serves as a vital repository for fish genetic resources. Its extensive water network and diverse climate have given rise to a unique fish composition and endemic species. In this study, we collected the cytochrome c oxidase subunit I (COI) sequences from 660 fish specimens in the Ili River Valley. The effectiveness of DNA barcoding in identifying fish species in the area was assessed by examining genetic distances, constructing phylogenetic trees, and performing ABGD (Automatic Barcode Gap Discovery) analyses, among other methods. In total, 20 species were identified, including one unidentified species (Silurus sp.). Except for Silurus asotus and Hypophthalmichthys molitrix (only one sample), the maximum intraspecific genetic distance among the remaining species was smaller than the minimum interspecific distance, which proves that the species exhibit obvious barcode gaps. In the Neighbor‐Joining trees, 20 species formed separate monophyletic branches. According to ABGD analysis, 660 sequences were categorized into 19 Operational Taxonomic Units, with Silurus sp. and S. asotus grouped into a single OTU. The Silurus in this study exhibits shared haplotypes and significant genetic divergence, suggesting the potential presence of cryptic species. Furthermore, the nucleotide diversity across all species fell below the threshold level, indicating that the local fish population is gradually declining. In conclusion, this study has demonstrated the effectiveness of DNA barcoding in identifying fish species in the Ili River Valley, providing valuable data to support the conservation of local fish resources.

Aim The aim of this study was to assess the clinical significance and prognostic value of the preoperative fibrinogen (FBG) level in patients with native valve infective endocarditis (NVIE) who underwent valve surgery. Methods This retrospective study included a total of 163 consecutive patients who were diagnosed with NVIE and underwent valve surgery from January 2019 to January 2022 in our hospital. The primary endpoint was all-cause mortality. Results All-cause mortality was observed in 9.2% of the patients (n = 15). Body mass index (BMI) was lower in the survival group (p = 0.025), whereas FBG (p = 0.008) and platelet count (p = 0.044) were significantly greater in the survival group than in the death group. Multivariate Cox proportional hazards analysis revealed that FBG (HR, 0.55; 95% CI, [0.32–0.94]; p = 0.029) was an independent prognostic factor for all-cause mortality. Furthermore, Kaplan‒Meier survival curve analysis revealed that patients with low FBG levels (3.99 g/L). In the trend analysis, the FBG tertiles were significantly related to all-cause mortality in all three adjusted models, and the p values for trend were 0.017, 0.016, and 0.028, respectively. Conclusion Preoperative FBG may serve as a prognostic factor for all-cause mortality, and an FBG concentration less than 3.28 g/L was associated with a greater risk of all-cause mortality in NVIE patients undergoing valve surgery.

Pullulan is a kind of natural polymer, which is widely used in medicine and food because of its solubility, plasticity, edible, non-toxicity and good biocompatibility. It is of great significance to improve the yield of pullulan by genetic modification of microorganisms. It was previously reported that Aureobasidium melanogenum TN3-1 isolated from honey-comb could produce high-yield of pullulan, but the molecular mechanisms of its production of pullulan had not been completely solved. In this study, the reported strains of Aureobasidium spp. were further compared and analyzed at genome level. It was found that genome duplication and genome genetic variations might be the crucial factors for the high yield of pullulan and stress resistance. This particular phenotype may be the result of adaptive evolution, which can adapt to its environment through genetic variation and adaptive selection. In addition, the TN3-1 strain has a large genome, and the special regulatory sequences of its specific genes and promoters may ensure a unique characteristics. This study is a supplement of the previous studies, and provides basic data for the research of microbial genome modification in food and healthcare applications.

BackgroundAcupuncture is a promising non-pharmaceutical complementary therapy in treating prolonged Disorders of consciousness (pDOC), but solid evidence to support its effectiveness and safety is still lacking. Thus, the purpose of this study is to investigate the efficacy and safety of acupuncture-assisted therapy for pDOC patients.MethodsA single-center, prospective, randomized, conventional-controlled, assessor-and-statistician-blinded trial has been designed and is being conducted at West China Hospital of Sichuan University. A total of 110 participants will be randomly assigned to the experimental group and the control group in a 1:1 allocation ratio and evaluated using Coma Recovery Scale-Revised (CRS-R) at 8 a.m., 12 p.m., and 4 p.m. on 2 consecutive days before enrollment to determine the consciousness level. The experimental group will receive acupuncture combined with conventional treatment, while the control group will receive only conventional treatment during the trial observation period. The treatment duration of both groups will be 20 days. Among them, the frequency of acupuncture-assisted therapy is once a day, with 10 consecutive sessions followed by a day’s rest for a total of 24 days. Data will be collected separately during baseline and after the final treatment. For data analysis, both Full Analysis Set (FAS) and Per Protocol Set (PPS) principles will be performed together by applying SPSS 27.0 software. The primary outcome measures are the changes of CRS-R before and after treatment, while the secondary outcome measures are the changes of Full Outline of Unresponsiveness Scale (FOUR), the changes of Nociception Coma Scale-Revised (NCS-R), the changes of Disability Rating Scale (DRS), the changes of Mismatch Negativity (MMN) and P300 before and after treatment, respectively.DiscussionThis trial aims to rationally assess the consciousness level from multiple 2 perspectives through subjective evaluation and objective detection by selecting several standardized clinical scales combined with Event-Related Potential (ERP) detection technology. In this way, we will be able to reduce the subjectivity of consciousness assessment and objectively evaluate the clinical efficacy of acupuncture-assisted therapy for pDOC. The study, if proven to be effective and safe enough, will provide a favorable evidence to guide medical decision-making choices and future researches.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2300076180.

This article discusses a case study of a 68-year-old male patient with lung squamous cell carcinoma (LUSC) who developed solitary renal metastasis. The importance of routine imaging for detecting asymptomatic renal metastasis is highlighted. The efficacy of various treatment options, including nephrectomy, stereotactic body radiation therapy, and cryoablation, is explored. The study underscores the need for a multidisciplinary team approach in managing LUSC with renal metastasis, due to the lack of clear treatment guidelines.

Fluoride exposure is widespread worldwide and poses a significant threat to organisms, particularly to their gastrointestinal tracts. However, due to limited knowledge of the mechanism of fluoride induced intestinal injury, it has been challenging to develop an effective treatment. To address this issue, we used a series of molecular biology in vitro and in vivo experiments. NaF triggered m6A mediated ferroptosis to cause intestinal damage. Mechanistically, NaF exposure increased the m6A level of SLC7A11 mRNA, promoted YTHDF2 binding to m6A-modified SLC7A11 mRNA, drove the degradation of SLC7A11 mRNA, and led to a decrease in its protein expression, which eventually triggers ferroptosis. Moreover, NaF aggravated ferroptosis of the colon after antibiotics destroyed the composition of gut microbiota. 16 S rRNA sequencing and SPEC-OCCU plots, Zi-Pi relationships, and Spearman correlation coefficients verified that Lactobacillus murinus (ASV54, ASV58, and ASV82) plays a key role in the response to NaF-induced ferroptosis. Collectively, NaF-induced gut microbiota alteration mediates severe intestinal cell injury by inducing m6A modification-mediated ferroptosis. Our results highlight a key mechanism of the gut in response to NaF exposure and suggest a valuable theoretical basis for its prevention and treatment.

Abstract The quantum computation of molecular response properties on near-term quantum hardware is a topic of substantial interest. Computing these properties directly in the frequency domain is desirable, but the circuits require large depth if the typical hardware gate set consisting of single- and two-qubit gates is used. While high-fidelity multipartite gates have been reported recently, their integration into quantum simulation and the demonstration of improved accuracy of the observable properties remains to be shown. Here, we report the application of a high-fidelity multipartite gate, the iToffoli gate, to the computation of frequency-domain response properties of diatomic molecules. The iToffoli gate enables a ~50% reduction in circuit depth and ~40% reduction in circuit execution time compared to the traditional gate set. We show that the molecular properties obtained with the iToffoli gate exhibit comparable or better agreement with theory than those obtained with the native CZ gates. Our work is among the first demonstrations of the practical usage of a native multi-qubit gate in quantum simulation, with diverse potential applications to near-term quantum computation.

Abstract Background This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores. Methods 46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman’s correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia. Results 1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P

Background Venous thromboembolism (VTE) has become the third most common cardiovascular disease after ischemic heart disease and stroke. Since the official launch of the National Programme for Prevention and Management of Pulmonary Embolism and Deep Vein Thrombosis in 2018, medical personnel have paid more attention to VTE, and the screening rate of VTE has also increased significantly. However, epidemiological investigations related to VTE are mostly limited to single center studies. There is still a lack of large-scale survey data on the prevalence of VTE involving different levels and properties of medical institutions. Objective To understand the prevalence and epidemiological characteristics of VTE in Jiaxing, and provide a basis for further prevention and treatment of VTE in this region. Methods A total of 731 755 discharged patients diagnosed with VTE from all secondary and above medical institutions in Jiaxing City in 2021 were included as the study subjects. General patient data and disease diagnosis-related grouping indicators reflecting the number of patients admitted to the hospital and the difficulty of diagnosis and treatment techniques were collected. Multiple linear regression analysis was used to explore influencing factors of the number of VTE patients in hospitals. Results According to inclusion and exclusion criteria, a total of 10 758 VTE patients were diagnosed. The median age of patients was 71 (62, 79) years. The number of VTE patients in general hospital was the highest, which amounting to 9 732 cases (90.46%), while the number of VTE patients in psychiatric hospital was the lowest at 53 cases (0.49%). The number of VTE patients in tertiary hospitals was higher than that in secondary hospitals [7 929 (73.70%) vs. 2 829 (26.30%) ]. The proportion of VTE patients in general hospital was the highest at 1.85%, and the lowest in maternal and child health hospital at 0.10%. The proportion of VTE patients in tertiary hospitals was higher than that in secondary hospitals, at 1.80% and 0.97%, respectively. The prevalence of VTE in different age groups was statistically significant (χ2=32 383.098, P

Abstract Background and purpose In recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression. Method C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR. Results This study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression. Conclusion Exercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice.

Abstract Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higher Bacteroides and lower Clostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors. Clostridium butyricum administration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.

Abstract Background Activation of VDR pathway was a promising anti-tumor therapy strategy. However, numerous clinical studies have demonstrated the effect of activating VDR is limited, which indicates that VDR plays a complex role in vivos. Methods We analyzed the TCGA database to examine the association between VDR expression and immune cell infiltration in pancreatic adenocarcinoma (PAAD). Western blot, ELISA, ChIP, and dual-luciferase reporter assays were performed to determine the mechanism of VDR regulating CCL20. Migration assay and immunofluorescence were used to investigate the role of CCL20 in M2 macrophage polarization and recruitment. We employed multiplexed immunohistochemical staining and mouse models to validate the correlation of VDR on macrophages infiltration in PAAD. Flow cytometry analysis of M2/M1 ratio in subcutaneous graft tumors. Results VDR is extensively expressed in PAAD, and patients with elevated VDR levels exhibited a significantly reduced overall survival. VDR expression in PAAD tissues was associated with increased M2 macrophages infiltration. PAAD cells overexpressing VDR promote macrophages polarization towards M2 phenotype and recruitment in vitro and vivo. Mechanistically, VDR binds to the CCL20 promoter and up-regulates its transcription. The effects of polarization and recruitment on macrophages can be rescued by blocking CCL20. Finally, the relationship between VDR and M2 macrophages infiltration was evaluated using clinical cohort and subcutaneous graft tumors. A positive correlation was demonstrated between VDR/CCL20/CD163 in PAAD tissues and mouse models. Conclusion High expression of VDR in PAAD promotes M2 macrophage polarization and recruitment through the secretion of CCL20, which activates tumor progression. This finding suggests that the combination of anti-macrophage therapy may improve the efficacy of VDR activation therapy in PAAD.

Abstract Over the past decade, learning engagement has received increasing attention from researchers. As a critical factor in college students’ academic achievement, learning engagement is significant in students’ long-term future development and social creativity. Present studies show that the overall level of college students’ learning engagement is low, which is highly unfavourable to educational quality and long-term development. There is no doubt about the position of the university library in academic circles. However, the influence of the university library environment on college students’ learning engagement has not been fully explored. The data in this study came from a survey of 45 Chinese universities. This paper investigates the relationship between the university library environment, students’ interaction, and students’ learning engagement. The results showed differences in Chinese college students’ learning engagement in liberal arts and sciences majors. The learning engagement of liberal arts majors is much lower than that of science students. We found that the library environment has an important influence on college students’ learning engagement. And the library environment can affect college students’ learning engagement through the intermediary role of interactive participation among students. In addition, for liberal arts students, the direct effect of the library environment on their learning engagement is more significant. However, for science students, the influence of the library environment on their learning engagement is more strongly intermediated by the students’ interaction. Therefore, future construction and renovation of library environments should cater not only to the diverse needs of different academic disciplines, especially liberal arts students who need special attention but also guide more students to interact friendly through the spatial characteristics of the library so as to improve the overall learning engagement of college students.

According to the infrared patch image (IPI) model theory, the infrared image background has a low rank and the target is sparse. The low-rank model can be used to separate the background and identify the target. However, in a noisy environment, the recognition effect will be affected. The higher the noise, the harder it would be to detect a small target. The residual strong fault and background edges could reduce the detection rate and increase false alarms. The traditional IPI model is adaptable to the background with the lower noise. This paper combines weighted nuclear norm minimization (WNNM) optimization with sparse representation based on the local IPI model. The background details are described more prominently by improving the nuclear norm weighting factor. The target is much easier to detect under the specific bright clouds and ground buildings background with high noise. At the same time, post-processing with image local contrast analysis is performed to compare traditional spatial filtering and local infrared patch image model algorithms. Our method has a good suppression effect on complex noise backgrounds and achieves a higher signal to clutter ratio gain (SCRG). It could also improve the target detection rate and reduce false alarms.

Lycophytes and ferns represent one of the earliest-diverging lineages of vascular plants, with the Lycopodiaceae family constituting the basal clade among lycophytes. In this research, we successfully assembled and annotated the complete Lycopodium japonicum Thunb. (L. japonicum) mitochondrial genome (mitogenome) utilizing PacBio HiFi sequencing data, resulting in a single circular molecule with a size of 454,458 bp. 64 unique genes were annotated altogether, including 34 protein-coding genes, 27 tRNAs and 3 rRNAs. It also contains 32 group II introns, all of which undergo cis-splicing. We identified 195 simple sequence repeats, 1,948 dispersed repeats, and 92 tandem repeats in the L. japonicum mitogenome. Collinear analysis indicated that the mitogenomes of Lycopodiaceae are remarkably conserved compared to those of other vascular plants. We totally identified 326 RNA editing sites in 31 unique protein-coding genes with 299 sites converting cytosine to uracil and 27 sites the reverse. Notably, the L. japonicum mitogenome has small amounts foreign DNA from plastid or nuclear origin, accounting for only 2.81% of the mitogenome. The maximum likelihood phylogenetic analysis based on 23 diverse land plant mitogenomes and plastid genomes supports the basal position of lycophytes within vascular plants and they form a sister clade to all other vascular lineages, which is consistent with the PPG I classification system. As the first reported mitogenome of Lycopodioideae subfamily, this study enriches our understanding of Lycopodium mitogenomes, and sets the stage for future research on mitochondrial diversity and evolution within the lycophytes and ferns.

BackgroundDepression is a chronic psychiatric condition that places significant burdens on individuals, families, and societies. The rapid evolution of non-invasive brain stimulation techniques has facilitated the extensive clinical use of Transcranial Magnetic Stimulation (TMS) for depression treatment. In light of the substantial recent increase in related research, this study aims to employ bibliometric methods to systematically review the global research status and trends of TMS in depression, providing a reference and guiding future studies in this field.MethodsWe retrieved literature on TMS and depression published between 1999 and 2023 from the Science Citation Index Expanded (SCIE) and Social Science Citation Index (SSCI) databases within the Web of Science Core Collection (WoSCC). Bibliometric analysis was performed using VOSviewer and CiteSpace software to analyze data on countries, institutions, authors, journals, keywords, citations, and to generate visual maps.ResultsA total of 5,046 publications were extracted covering the period from 1999 to 2023 in the field of TMS and depression. The publication output exhibited an overall exponential growth trend. These articles were published across 804 different journals, BRAIN STIMULATION is the platform that receives the most articles in this area. The literature involved contributions from over 16,000 authors affiliated with 4,573 institutions across 77 countries. The United States contributed the largest number of publications, with the University of Toronto and Daskalakis ZJ leading as the most prolific institution and author, respectively. Keywords such as “Default Mode Network,” “Functional Connectivity,” and “Theta Burst” have recently garnered significant attention. Research in this field primarily focuses on TMS stimulation patterns, their therapeutic efficacy and safety, brain region and network mechanisms under combined brain imaging technologies, and the modulation effects of TMS on brain-derived neurotrophic factor (BDNF) and neurotransmitter levels.ConclusionIn recent years, TMS therapy has demonstrated extensive potential applications and significant implications for the treatment of depression. Research in the field of TMS for depression has achieved notable progress. Particularly, the development of novel TMS stimulation patterns and the integration of TMS therapy with multimodal techniques and machine learning algorithms for precision treatment and investigation of brain network mechanisms have emerged as current research hotspots.

Digital soil mapping (DSM) relies on machine-learning and geostatistics to represent soil property observations across space. DSM techniques are powerful but often empirical, being limited to the quality and density of point samples. Water dynamics are closely related to soil variability, and the physics that govern water movement are well known. Hydrological properties can hence be simulated by physical models through space and time, unveiling key characteristics about soils. We propose the use of hydrologic models to map soils across the surface (2D), depth (1D), and time (1D)–which provides a 4D approach to digital soil mapping (4DSM). The Distributed Hydrology Soil Vegetation Model (DHSVM) was applied to a watershed currently under pasture. Moisture sensors and wells were installed at different depths in the watershed on summit, sideslope and toeslope positions to validate the model. DHSVM simulations of soil moisture distribution and depth to saturation were performed during the hydrological year (October 2008-September 2009). Clusters of similar pixels based on soil moisture values were determined using Dynamic Time Warping (DTW) to align temporal data and K-means. Clustering was performed both seasonally and for the entire year. Temporal patterns simulated by DHSVM matched measurements given by moisture sensors and wells. Seasonal clusters differed from the annual cluster. Distinct clusters were observed for each season and with depth, showing that spatiotemporal soil variability is lost when statically assessing soils. Spatiotemporal clusters corroborated field observations of fragipan occurrence not explicitly spatially mapped by Soil Survey Geographic Database (SSURGO). If a connection can be made between water and soils, static and dynamic soil variability can be predicted using physically based hydrologic models. Hydrologic models can benefit soil mapping by enabling reliable 4D simulation of water dynamics, which are fundamental to soil variability and soil classification and directly relate to biological, physical and chemical soil processes not captured by typical soil sampling protocols.

Multidrug resistant bacteria have been a global health threat currently and frontline clinical treatments for these infections are very limited. To develop potent antibacterial agents with new bactericidal mechanisms is thus needed urgently to address this critical antibiotic resistance challenge. Natural products are a treasure of small molecules with high bioactive and low toxicity. In the present study, we demonstrated that a natural compound, honokiol, showed potent antibacterial activity against a number of Gram-positive bacteria including MRSA and VRE. Moreover, honokiol in combination with clinically used β-lactam antibiotics exhibits strong synergistic antimicrobial effects against drug-resistant S. aureus strains. Biochemical studies further reveal that honokiol may disrupt the GTPase activity, FtsZ polymerization, cell division. These biological impacts induced by honokiol may ultimately cause bacterial cell death. The in vivo antibacterial activity of honokiol against S. aureus infection was also verified with a biological model of G. mellonella larvae. The in vivo results support that honokiol is low toxic against the larvae and effectively increases the survival rate of the larvae infected with S. aureus. These findings demonstrate the potential of honokiol for further structural advancement as a new class of antibacterial agents with high potency against multidrug-resistant bacteria.

The study examined the impact of adding cattle manure to the composting process of Agaricus bisporus mushroom substrate on compost humification. A control group CK comprised entirely of Agaricus bisporus mushroom substrate, while the experimental group CD (70 percent Agaricus bisporus mushroom substrate and 30 percent cattle manure) comprised the two composting treatments that were established. The study determined that the addition of cow dung has promoted the formation of humus components. Particularly, humic substance (HS-C) and humic acid (HA) increased by 41.3 and 74.7%, respectively, and the ratio of humic acid to fulvic acid (HA/FA) also increased by 2.78. It showed that the addition of cow dung accelerated the synthesis and decomposition of precursors, such as polysaccharides, polyphenols, and reducing sugars. Thereby promoting the formation of humic acid. Network analysis revealed that adding cow dung promoted microbial interactions increased the complexity and stability of the bacterial and fungal symbiotic network, enhanced cooperation and reciprocity among microbes, and assisted in transforming fulvic acid (FA) components. Structural equation modeling (SEM) is a multivariate data analysis method for analyzing complex relationships among constructs and core indicators. SEM illustrated that introducing cattle manure into the composting process resulted in alterations to the correlation between physicochemical parameters and the microbial community, in addition to humus formation. Polysaccharides are the primary precursors for polymerization to form HA, which is an essential prerequisite for the conversion of fulvic acid to humic acid. Additionally, microbes affected the formation of humus, with bacteria substantially more influential than fungi. These findings provide new ideas for regulating the degree of humification in the composting process and have important practical implications for optimizing mushroom cultivation and composting techniques today.

Aims: Vascular calcification is strongly linked to the development of major adverse cardiovascular events, but effective treatments are lacking. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an emerging category of oral hypoglycemic drugs that have displayed marked effects on metabolic and cardiovascular diseases, including recently reported vascular medial calcification. However, the roles and underlying mechanisms of SGLT2 inhibitors in vascular calcification have not been fully elucidated. Thus, we aimed to further determine whether SGLT2 inhibitors protect against vascular calcification and to investigate the mechanisms involved. Methods and results: A computed tomography angiography investigation of coronary arteries from 1554 patients with type 2 diabetes revealed that SGLT2 inhibitor use was correlated with a lower Agatston calcification score. In the vitamin D3 overdose, 5/6 nephrectomy chronic kidney disease-induced medial calcification and Western diet-induced atherosclerotic intimal calcification models, dapagliflozin (DAPA) substantially alleviated vascular calcification in the aorta. Furthermore, we showed that DAPA reduced vascular calcification via Runx2-dependent osteogenic transdifferentiation in vascular smooth muscle cells (VSMCs). Transcriptome profiling revealed that thioredoxin domain containing 5 (TXNDC5) was involved in the attenuation of vascular calcification by DAPA. Rescue experiments showed that DAPA-induced TXNDC5 downregulation in VSMCs blocked the protective effect on vascular calcification. Furthermore, TXNDC5 downregulation disrupted protein folding-dependent Runx2 stability and promoted subsequent proteasomal degradation. Moreover, DAPA downregulated TXNDC5 expression via amelioration of oxidative stress and ATF6-dependent endoplasmic reticulum stress. Consistently, the class effects of SGLT2 inhibitors on vascular calcification were validated with empagliflozin in intimal and medial calcification models. Conclusions: SGLT2 inhibitors ameliorate vascular calcification through blocking endoplasmic reticulum stress-dependent TXNDC5 upregulation and promoting subsequent Runx2 proteasomal degradation, suggesting that SGLT2 inhibitors are potentially beneficial for vascular calcification treatment and prevention.

Objective: A retrospective analysis was performed to explore the clinical effect of the Posterior Nasal Nerve (PNN) resection combined with hormone transnasal nebulization on Difficult-to-Treat Rhinosinusitis (DTRS). Methods: A total of 120 DTRS patients were selected and divided into a control group (n = 60) and a study group (n = 60) according to different treatments. The control group patients were treated via PNN resection, followed by normal saline transnasal nebulization; the study group patients were given PNN resection and then treated with budesonide suspension transnasal nebulization. Subsequently, the comparison was performed between the two groups in terms of (1) Clinical baseline characteristics; (2) Sino-nasal Outcome Test (SNOT)-22 scores before treatment and after 3-months, 6-months and 12-months of treatment; (3) Lund-MacKay scores before treatment and after 10, 30, 90, and 180 days of treatment; (4) Incidence of adverse reactions during treatment. Results: There was no significant difference in SNOT-22 or Lund-Kennedy scores between the two groups before treatment (p > 0.05). After treatment, the SNOT-22 and Lund-Kennedy scores of the control and the study groups were decreased, and compared with the control group, the SNOT-22 and Lund-Kennedy scores in the study group improved more significantly (p

The optimization dispatching problem of the regional distribution network (DN) interconnection with the microgrid (MG) is studied in this paper. By installing flexible interconnection devices based on the soft open point (SOP) at the boundaries of DNs, the flexible interconnection can be achieved between distribution networks, and the distribution zoning model is established. A multiobjective DN–MG system optimization dispatching model for multi-area DNs considering distributed resources is established based on the distribution zoning model. By introducing intermediate coupling variables, the optimization dispatching problem of the DN–MG system is decomposed into MG sub-area optimization problems and DN sub-area optimization problems. On the basis of the above, a method based on the alternating direction method of multipliers (ADMM) is proposed to solve the optimization dispatching model. Finally, simulation verification shows that by application of the proposed method, the economic efficiency of the DN–MG system is improved effectively.

Multiple microgrids interconnect to form a microgrid cluster. To fully exploit the comprehensive benefits of the microgrid cluster, it is imperative to optimize dispatch based on the matching degree between the sources and loads of each microgrid. The power of distributed energy sources such as wind and photovoltaic systems and the sensitive loads in microgrids is related to the regional weather characteristics. Given the relatively small geographical scope of microgrid areas and the fact that distributed energy sources and loads within the grid share the same weather characteristics, simultaneous ultra-short-term forecasting of power for both sources and loads is essential in the same environmental context. Firstly, the introduction of the multi-variable uniform information coefficient (MV-UIC) is proposed for extracting the correlation between weather characteristics and the sequences of source and load power. Subsequently, the application of factor analysis (FA) is introduced to reduce the dimensionality of input feature variables. Drawing inspiration from the concept of combination forecasting models, a combined forecasting model based on Error Back Propagation Training (BP), Long Short-Term Memory (LSTM), and Bidirectional Long Short-Term Memory Neural Network (BiLSTM) is constructed. This model is established on the MV-UIC-FA foundation for the joint ultra-short-term forecasting of source and load power in microgrids. Simulation is conducted using the DTU 7K 47-bus system as an example to analyze the accuracy, applicability, and effectiveness of the proposed joint forecasting method for sources and loads.

Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50 mg·kg−1·d−1, ig) or the positive control sulfasalazine (500 mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1β. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1β, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment.

Abstract Background Cholangiocarcinoma (CCA) is a biliary epithelial malignant tumor with an increasing incidence worldwide. Therefore, further understanding of the molecular mechanisms of CCA progression is required to identify new therapeutic targets. Methods The expression of RPL35A in CCA and para-carcinoma tissues was detected by immunohistochemical staining. IP-MS combined with Co-IP identified downstream proteins regulated by RPL35A. Western blot and Co-IP of CHX or MG-132 treated CCA cells were used to verify the regulation of HSPA8 protein by RPL35A. Cell experiments and subcutaneous tumorigenesis experiments in nude mice were performed to evaluate the effects of RPL35A and HSPA8 on the proliferation, apoptosis, cell cycle, migration of CCA cells and tumor growth in vivo. Results RPL35A was significantly upregulated in CCA tissues and cells. RPL35A knockdown inhibited the proliferation and migration of HCCC-9810 and HUCCT1 cells, induced apoptosis, and arrested the cell cycle in G1 phase. HSPA8 was a downstream protein of RPL35A and overexpressed in CCA. RPL35A knockdown impaired HSPA8 protein stability and increased HSPA8 protein ubiquitination levels. RPL35A overexpression promoted CCA cell proliferation and migration. HSPA8 knockdown inhibited CCA cell proliferation and migration, and reversed the promoting effect of RPL35A. Furthermore, RPL35A promoted tumor growth in vivo. In contrast, HSPA8 knockdown suppressed tumor growth, while was able to restore the effects of RPL35A overexpression. Conclusion RPL35A was upregulated in CCA tissues and promoted the progression of CCA by mediating HSPA8 ubiquitination.

Abstract The copper (Cu)-catalyzed electrochemical CO2 reduction provides a route for the synthesis of multicarbon (C2+) products. However, the thermodynamically favorable Cu surface (i.e. Cu(111)) energetically favors single-carbon production, leading to low energy efficiency and low production rates for C2+ products. Here we introduce in situ copper faceting from electrochemical reduction to enable preferential exposure of Cu(100) facets. During the precatalyst evolution, a phosphate ligand slows the reduction of Cu and assists the generation and co-adsorption of CO and hydroxide ions, steering the surface reconstruction to Cu (100). The resulting Cu catalyst enables current densities of > 500 mA cm−2 and Faradaic efficiencies of >83% towards C2+ products from both CO2 reduction and CO reduction. When run at 500 mA cm−2 for 150 hours, the catalyst maintains a 37% full-cell energy efficiency and a 95% single-pass carbon efficiency throughout.

Abstract Background Phosphatase and tensin homolog deleted on chromosome ten (PTEN) serves as a powerful tumor suppressor, and has been found to be downregulated in human bladder cancer (BC) tissues. Despite this observation, the mechanisms contributing to PTEN’s downregulation have remained elusive. Methods We established targeted genes’ knockdown or overexpressed cell lines to explore the mechanism how it drove the malignant transformation of urothelial cells or promoted anchorageindependent growth of human basal muscle invasive BC (BMIBC) cells. The mice model was used to validate the conclusion in vivo. The important findings were also extended to human studies. Results In this study, we discovered that mice exposed to N-butyl-N-(4-hydroxybu-tyl)nitrosamine (BBN), a specific bladder chemical carcinogen, exhibited primary BMIBC accompanied by a pronounced reduction in PTEN protein expression in vivo. Utilizing a lncRNA deep sequencing high-throughput platform, along with gain- and loss-of-function analyses, we identified small nucleolar RNA host gene 1 (SNHG1) as a critical lncRNA that might drive the formation of primary BMIBCs in BBN-treated mice. Cell culture results further demonstrated that BBN exposure significantly induced SNHG1 in normal human bladder urothelial cell UROtsa. Notably, the ectopic expression of SNHG1 alone was sufficient to induce malignant transformation in human urothelial cells, while SNHG1 knockdown effectively inhibited anchorage-independent growth of human BMIBCs. Our detailed investigation revealed that SNHG1 overexpression led to PTEN protein degradation through its direct interaction with HUR. This interaction reduced HUR binding to ubiquitin-specific peptidase 8 (USP8) mRNA, causing degradation of USP8 mRNA and a subsequent decrease in USP8 protein expression. The downregulation of USP8, in turn, increased PTEN polyubiquitination and degradation, culminating in cell malignant transformation and BMIBC anchorageindependent growth. In vivo studies confirmed the downregulation of PTEN and USP8, as well as their positive correlations in both BBN-treated mouse bladder urothelium and tumor tissues of bladder cancer in nude mice. Conclusions Our findings, for the first time, demonstrate that overexpressed SNHG1 competes with USP8 for binding to HUR. This competition attenuates USP8 mRNA stability and protein expression, leading to PTEN protein degradation, consequently, this process drives urothelial cell malignant transformation and fosters BMIBC growth and primary BMIBC formation.

Abstract Preeclampsia is a multifactorial and heterogeneous complication of pregnancy. Here, we utilize single-cell RNA sequencing to dissect the involvement of circulating immune cells in preeclampsia. Our findings reveal downregulation of immune response in lymphocyte subsets in preeclampsia, such as reduction in natural killer cells and cytotoxic genes expression, and expansion of regulatory T cells. But the activation of naïve T cell and monocyte subsets, as well as increased MHC-II-mediated pathway in antigen-presenting cells were still observed in preeclampsia. Notably, we identified key monocyte subsets in preeclampsia, with significantly increased expression of angiogenesis pathways and pro-inflammatory S100 family genes in VCAN+ monocytes and IFN+ non-classical monocytes. Furthermore, four cell-type-specific machine-learning models have been developed to identify potential diagnostic indicators of preeclampsia. Collectively, our study demonstrates transcriptomic alternations of circulating immune cells and identifies immune components that could be involved in pathophysiology of preeclampsia.

Although deep learning methods based on single sensors are widely applied in fault diagnosis, leveraging multi-sensor data to learn useful information remains a challenge. To fully utilize multi-sensor information, this paper proposes a lightweight improvement of the EfficientNetV2 architecture, combined with sensor fusion technology and transfer learning techniques, to develop an efficient and reliable new method specifically for motor fault diagnosis. First, the continuous wavelet transform is utilized to convert the signals from various sensors into time-frequency images, and the Mallat algorithm is employed to decompose each image into sub-band coefficients at different levels. Secondly, a fusion reconstruction method is constructed using coefficient absolute maximum and weighted average fusion rules to integrate the sub-band coefficients of multi-sensor time-frequency images at different levels. Subsequently, EfficientNetV2 is improved to enhance the model’s feature extraction capabilities, computational efficiency, and achieve lightweight effects. The EfficientNetV2-M0 network modifies the model’s depth and width multiplicity factors, reducing parameters and computational complexity. Furthermore, this network incorporates Diverse Branch Block (DBB) and Multidimensional Collaborative Attention (MCA) to enhance feature extraction under complex backgrounds, and the maximum cross-entropy loss function is improved by using label smoothing and focal loss to dynamically adjust the classification weights for improved accuracy. The network leverages pre-trained models obtained through transfer learning techniques for deployment, combining multi-sensor information fusion and the improved lightweight model for fault diagnosis applications. Finally, a fault diagnosis experiment is conducted using a motor state dataset. The experimental results demonstrate that the proposed method outperforms the control method in terms of diagnostic performance and robustness, with an accuracy of 100%, and it exhibits excellent performance even under conditions of small sample data, with an accuracy of 98.81%.