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Objective To investigate the efficacy and safety of ofatumumab in the treatment of neuromyelitis optica spectrum disorders (NMOSDs). Methods The clinical data of 25 patients with NMOSDs hospitalized in The First Affiliated Hospital of Zhengzhou University from April 2022 to March 2023 and treated with ofatumumab were retrospectively analyzed. They were divided into 2 groups, Group A with 12 cases receiving regular medication, and Group B with 13 cases receiving medication based on the percentage of CD19+B lymphocytes. Annual relapse rate (ARR), the number of relapses, the frequency and time of relapses, and the symptoms of relapses were calculated before and at one year of medication. The neurological function was assessed by Expanded Disability Status Scale (EDSS) before and at one year of medication. The adverse drug reactions were recorded during medication. Results After one year treatment with ofatumumab, 3 patients (12%) experienced recurrence. One patient in Group A experienced recurrence twice, one month and 5 months after treatment, respectively. At the second recurrence, the percentage of CD19+B lymphocytes was 2.80%. Two patients in Group B experienced recurrence, one patient relapsed twice at 2 and 6 months after medication. The percentage of CD19+B lymphocytes was 0.80% and 0.21%, respectively; another patient relapsed once at 2 months after medication. At the time of recurrence, the percentage of CD19+B lymphocytes was 0.70%. There was a statistically significant difference in ARR before and after one year treatment (F = 29.061, P = 0.000). After one year's treatment, the ARR of Group A (t = 13.215, P = 0.001) and Group B (t = 19.259, P = 0.000) was decreased than before. There were 8 cases of the injection site pain, 3 cases of fever after injection, and one case of headache after injection. There were no serious adverse reactions such as disability and death, and EDSS scores were not increased. Conclusions Continuous administration of ofatumumab every 3 months or based on the percentage of CD19+B lymphocyte can reduce recurrence. Combination with corticosteroids should be alert to the risk of infection.

Abstract The DC multi‐port converter's applications are increasing owing to its favourable features, including variable control mode, high power density, and bi‐directional power supply. On the other hand, the impedance interaction between each port of the electrolytic capacitor‐less DC multi‐port converter may generate an instability. To address the above mentioned problem, a method is proposed in this paper for reshaping the impedances of the energy storage converter by constructing a virtual impedance connected in parallel with the output impedance of the electrolytic capacitor‐less DC multi‐port converter. Furthermore, this paper introduces the stability criterion based on the unified impedance theory, which classifies a converter as either the bus current‐controlled converter or the bus voltage‐controlled converter. The proposed control approaches raise the magnitude of the output impedance of the electrolytic capacitor‐less DC multi‐port converter to satisfy the unified impedance theory criterion without modifying each port. The simulation results show that the proposed method is better than the traditional methods, and comprehensive experimental results are provided to validate the proposed methods.

In this study, a comprehensive analysis is presented on the complete mitochondrial genome and phylogenetic relationships of Devario shanensis, an endemic species to the Irrawaddy drainage in southwestern China. The complete mitogenome sequence of D. shanensis was sequenced to be 16,860 bp long and encompassed 13 protein-coding genes, 22 tRNA genes, two rRNA genes and a non-coding control region. The overall AT content (61.1%) was much higher than GC content (38.9%). Phylogenetic analyses employing maximum-likelihood and Bayesian inference methods on the complete mitogenomes, including D. shanensis and 13 other species, unveiled a close genomic relationship between D. shanensis and Devario interruptus. This work will contribute to the genetic resource enrichment and phylogenetic researches on genus Devario.

Abstract Recent research in computational imaging largely focuses on developing machine learning (ML) techniques for image recognition in the medical field, which requires large-scale and high-quality training datasets consisting of raw images and annotated images. However, suitable experimental datasets for cervical spine X-ray are scarce. We fill the gap by providing an open-access Cervical Spine X-ray Atlas (CSXA), which includes 4963 raw PNG images and 4963 annotated images with JSON format (JavaScript Object Notation). Every image in the CSXA is enriched with gender, age, pixel equivalent, asymptomatic and symptomatic classifications, cervical curvature categorization and 118 quantitative parameters. Subsequently, an efficient algorithm has developed to transform 23 keypoints in images into 77 quantitative parameters for cervical spine disease diagnosis and treatment. The algorithm’s development is intended to assist future researchers in repurposing annotated images for the advancement of machine learning techniques across various image recognition tasks. The CSXA and algorithm are open-access with the intention of aiding the research communities in experiment replication and advancing the field of medical imaging in cervical spine.

Abstract Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.

Background Gastrointestinal dysfunction is a very common complication in peritoneal dialysis patients, which not only seriously affects the appetite and mood of patients, but also induces malnutrition, dehydration, electrolyte disorders, or systemic inflammatory reactions, and even leads to a decrease in the effectiveness of peritoneal dialysis, thus increasing the difficulty of medical treatment and lowering the patients' standard of living. Objective To analyse the clinical characteristics and influencing factors of patients with peritoneal dialysis-associated gastrointestinal dysfunction, and provide reference for the clinical diagnosis and treatment of peritoneal dialysis-associated gastrointestinal dysfunction. Methods A retrospective study was conducted to select 304 uremic patients who underwent continuous ambulatory peritoneal dialysis in the Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from 2019-09-01 to 2021-09-01. The patients were divided into the gastrointestinal dysfunction group and non-gastrointestinal dysfunction according to the combination of gastrointestinal dysfunction. General data, comorbidities, laboratory test indexes, and dialysis adequacy-related indexes of the two groups of patients were collected and compared. SPSS 23.0 software was used to statistically analyze the clinical data, the clinical characteristics of peritoneal dialysis-associated gastrointestinal dysfunction, and multivariate Logistic regression analysis was used to explore the factors influencing the occurrence of peritoneal dialysis-associated gastrointestinal dysfunction in patients with uremia. Results A total of 304 peritoneal dialysis patients were included, of which 189 (62.2%) were in the gastrointestinal dysfunction group, with the median age of 62 (52, 67) years. The differences in age, proportions of primary diabetic nephropathy and combined hypertension and coronary artery disease between the two groups were statistically significant (P

Abstract Background To the best of our knowledge, no study has investigated the potential joint effect of large for gestational age (LGA) and assisted reproductive technology (ART) on the long-term health of children. Methods This was a prospective cohort study that recruited children whose parents had received ART treatment in the Center for Reproductive Medicine, Shandong Provincial Hospital, affiliated to Shandong University, between January 2006 and December 2017. Linear mixed model was used to compare the main outcomes. The mediation model was used to evaluate the intermediary effect of body mass index (BMI). Results 4138 (29.5%) children born LGA and 9910 (70.5%) children born appropriate for gestational age (AGA) were included in the present study. The offspring ranged from 0.4 to 9.9 years. LGAs conceived through ART were shown to have higher BMI, blood pressure, fasting blood glucose, fasting insulin, and homeostatic model assessment of insulin resistance values, even after controlling for all covariates. The odds of overweight and insulin resistance are also higher in LGA subjects. After adjusting for all covariates, LGAs conceived through ART had BMI and BMI z-scores that were 0.48 kg/m2 and 0.34 units greater than those of AGAs, respectively. The effect of LGA on BMI was identified as early as infancy and remained consistently significant throughout pre-puberty. Conclusions Compared to AGA, LGA children conceived from ART were associated with increased cardiovascular-metabolic events, which appeared as early as infancy and with no recovery by pre-puberty.

Traumatic central nervous system injury, including traumatic brain injury and spinal cord injury, has extremely high disability and mortality rates. The huge medical expenses and sequelae further aggravate the economic and psychological burden of patients and their families. Current treatments for traumatic central nervous system injury include surgical therapy, physical therapy, medication and post-rehabilitation treatment, but none of them can achieve ideal efficacy, and more effective treatment is urgently needed. Ferroptosis, as one of the newly discovered modes of programmed cell death, has been shown to play a crucial role in secondary injury to the traumatic central nervous system, but its clinical transformation is limited. This article summarizes the research results of ferroptosis inhibitors, points out the types and effects of them, to provide new ideas for clinical treatment of traumatic central nervous system injury and drug development.

Abstract Although messenger RNA translation is tightly regulated to preserve protein synthesis and cellular homeostasis, chronic exposure to interferon‐γ (IFN‐γ) in several cancers can lead to tryptophan (Trp) shortage via the indoleamine‐2,3‐dioxygenase (IDO)‐ kynurenine pathway and therefore promotes the production of aberrant peptides by ribosomal frameshifting and tryptophan‐to‐phenylalanine (W>F) codon reassignment events (substitutants) specifically at Trp codons. However, the effect of Trp depletion on the generation of aberrant peptides by ribosomal mistranslation in gastric cancer (GC) is still obscure. Here, it is shows that the abundant infiltrating lymphocytes in EBV‐positive GC continuously secreted IFN‐γ, upregulated IDO1 expression, leading to Trp shortage and the induction of W>F substitutants. Intriguingly, the production of W>F substitutants in EBV‐positive GC is linked to antigen presentation and the activation of the mTOR/eIF4E signaling pathway. Inhibiting either the mTOR/eIF4E pathway or EIF4E expression counteracted the production and antigen presentation of W>F substitutants. Thus, the mTOR/eIF4E pathway exposed the vulnerability of gastric cancer by accelerating the production of aberrant peptides and boosting immune activation through W>F substitutant events. This work proposes that EBV‐positive GC patients with mTOR/eIF4E hyperactivation may benefit from anti‐tumor immunotherapy.

Transmembrane channel-like (TMC) proteins are a highly conserved ion channel family consisting of eight members (TMC1–TMC8) in mammals. TMC1/2 are components of the mechanotransduction channel in hair cells, and mutations of TMC1/2 cause deafness in humans and mice. However, the physiological roles of other TMC proteins remain largely unknown. Here, we show that Tmc7 is specifically expressed in the testis and that it is required for acrosome biogenesis during spermatogenesis. Tmc7−/− mice exhibited abnormal sperm head, disorganized mitochondrial sheaths, and reduced number of elongating spermatids, similar to human oligo-astheno-teratozoospermia. We further demonstrate that TMC7 is colocalized with GM130 at the cis-Golgi region in round spermatids. TMC7 deficiency leads to aberrant Golgi morphology and impaired fusion of Golgi-derived vesicles to the developing acrosome. Moreover, upon loss of TMC7 intracellular ion homeostasis is impaired and ROS levels are increased, which in turn causes Golgi and endoplasmic reticulum stress. Taken together, these results suggest that TMC7 is required to maintain pH and ion homeostasis, which is needed for acrosome biogenesis. Our findings unveil a novel role for TMC7 in acrosome biogenesis during spermiogenesis.

To address the challenges of multiple design variables, long evaluation times, and poor global search capability of traditional surrogate-assisted algorithms that rely on the complete substitution of accurate function evaluations in the turbine aerodynamic optimization process, a pre-screening surrogate-assisted elitist preservation genetic algorithm (pre-SAEGA) optimizer is proposed. Pre-screening strategy in the pre-SAEGA can screen samples instead of directly estimating them, thereby reducing expensive evaluations in each generation. The directly manipulated free-form deformation (DFFD) method is applied to parameterized multi-stage axial turbines, and multi-degree-of-freedom flexible control is realized. Combining the pre-SAEGA with the DFFD method, a data-driven multi-stage axial turbine optimization platform is established. A two-stage axial turbine is the research object, and 44 design variables are selected for the combined optimization design of flow path and blade rows. The results show that the isentropic efficiency and flow rate improve by 1.33 % and 1.81 % respectively, and the pressure ratio decreases by 0.47 % at the turbine design point. The presented optimization platform not only improves the aerodynamic optimization effect but also significantly reduces the number of design variables and real evaluation samples, making it suitable for solving multi-stage turbine optimization problems with multiple degrees of freedom.

Abstract The progression of spermatogenesis along specific developmental trajectories depends on the coordinated regulation of pre‐mRNA alternative splicing (AS) at the post‐transcriptional level. However, the fundamental mechanism of AS in spermatogenesis remains to be investigated. Here, it is demonstrated that CWF19L2 plays a pivotal role in spermatogenesis and male fertility. In germline conditional Cwf19l2 knockout mice exhibiting male sterility, impaired spermatogenesis characterized by increased apoptosis and decreased differentiated spermatogonia and spermatocytes is observed. That CWF19L2 interacted with several spliceosome proteins to participate in the proper assembly and stability of the spliceosome is discovered. By integrating RNA‐seq and LACE‐seq data, it is further confirmed CWF19L2 directly bound and regulated the splicing of genes related to spermatogenesis (Znhit1, Btrc, and Fbxw7) and RNA splicing (Rbfox1, Celf1, and Rbm10). Additionally, CWF19L2 can indirectly amplify its effect on splicing regulation through modulating RBFOX1. Collectively, this research establishes that CWF19L2 orchestrates a splicing factor network to ensure accurate pre‐mRNA splicing during the early steps of spermatogenesis.

BackgroundConstipation is affected by a number of risk variables, including cardiovascular disease and growth factors. However, the impacts of gut flora on constipation incidence has not been shown. This work, Single-Variable Mendelian Randomization (SVMR) was utilized to estimate the causal relationship between the Eubacterium genus or Rumphococcus, and constipation.MethodsData for constipation, Eubacterium genus and Rumphococcus were taken from the Integrated Epidemiology Unit (IEU) open GWAS database. Including 218,792 constipation samples, and there were 16,380,466 Single Nucleotide Polymorphisms (SNPs) for constipation. The ids of Eubacterium genus and Rumphococcus were sourced from MiBioGen database. The sample count for the Eubacterium genus was 17,380, with 656 SNPs. In addition, the sample size for Rumphococcus was 15,339, with 545 SNPs. The SVMR was performed to assess the risk of Eubacterium genus and Rumphococcus in constipation using weighted median, MR Egger, simple mode, inverse variance weighted (IVW), and weighted mode. Finally, we did a sensitivity analysis that included a heterogeneity, horizontal pleiotropy, and Leave-One-Out (LOO) test to examine the viability of the MR data.ResultsThe SVMR revealed that the Eubacterium genus and Rumphococcus were causally connected to constipation, with Rumphococcus (P = 0.042, OR = 1.074) as a hazardous factor and Eubacterium genus (P = 0.004, OR = 0.909) as a safety factor. Sensitivity tests then revealed the absence of variability between the constipation and the exposure factors (Eubacterium genus and Rumphococcus). Additionally, there were no other confounding factors and the examined SNPs could only influence constipation through the aforementioned exposure factors, respectively. As a result, the MR results were fairly robust.ConclusionOur investigation verified the causal links between the Eubacterium genus or Rumphococcus, and constipation, with greater Rumphococcus expression increasing the likelihood of constipation and the opposite being true for the Eubacterium genus.

Major depression is a complex psychiatric disorder that includes genetic, neurological, and cognitive factors. Early detection and intervention can prevent progression, and help select the best treatment. Traditional clinical diagnosis tends to be subjective and misdiagnosed. Based on this, this study leverages clinical scale assessments and sequencing data to construct disease prediction models. Firstly, data undergoes preprocessing involving normalization and other requisite procedures. Feature engineering is then applied to curate subsets of features, culminating in the construction of a model through the implementation of machine learning and deep learning algorithms. In this study, 18 features with significant differences between patients and healthy controls were selected. The depression recognition model was constructed by deep learning with an accuracy of 87.26 % and an AUC of 91.56 %, which can effectively distinguish patients with depression from healthy controls. In addition, 33 features selected by recursive feature elimination method were used to construct a prognostic effect model of patients after 2 weeks of treatment, with an accuracy of 75.94 % and an AUC of 83.33 %. The results show that the deep learning algorithm based on clinical and sequencing data has good accuracy and provides an objective and accurate method for the diagnosis and pharmacodynamic prediction of depression. Furthermore, the selected differential features can serve as candidate biomarkers to provide valuable clues for diagnosis and efficacy prediction.

The crystalline agents can be used to improve the concrete frost resistance by its densification effect on the microstructure of concrete, while the effect of which depends on the type and penetration process of the crystalline agents. This study, therefore, aimed to investigate the effect of two types of crystalline materials, in terms of organic and inorganic one, and two kinds of penetration methods including surface coating and soaking, in concrete. In addition to freeze-thaw test and electric flux test, the thermal gravity analysis, mercury intrusion porosimetry and scanning electron microscope were carried out. The results showed that after vacuum drying and soaking treatment, the material’s penetration depth has reached 7 mm. Deeper penetration depth shifted the freeze-thaw failure mode sudden to gradual, significantly enhancing frost resistance as a result. Among them, organic crystalline agent increased frost resistance by 2.5 times and decreased electrical flux by approximately 90 %, while inorganic crystalline agent only enhanced frost resistance by 1.5 times and reduced electrical flux by only about 37 %. From a reaction mechanism perspective, the hydrophobic layer within the pores formed by organic crystalline material has the most contribution, in which the needle-like substances generated by inorganic one filled the pores with limited effect to barrier water.

Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.

Abstract Surrogate models play a vital role in overcoming the computational challenge in designing and analyzing nonlinear dynamic systems, especially in the presence of uncertainty. This paper presents a comparative study of different surrogate modeling techniques for nonlinear dynamic systems. Four surrogate modeling methods, namely, Gaussian process (GP) regression, a long short-term memory (LSTM) network, a convolutional neural network (CNN) with LSTM (CNN-LSTM), and a CNN with bidirectional LSTM (CNN-BLSTM), are studied and compared. All these model types can predict the future behavior of dynamic systems over long periods based on training data from relatively short periods. The multi-dimensional inputs of surrogate models are organized in a nonlinear autoregressive exogenous model (NARX) scheme to enable recursive prediction over long periods, where current predictions replace inputs from the previous time window. Three numerical examples, including one mathematical example and two nonlinear engineering analysis models, are used to compare the performance of the four surrogate modeling techniques. The results show that the GP-NARX surrogate model tends to have more stable performance than the other three deep learning (DL)-based methods for the three particular examples studied. The tuning effort of GP-NARX is also much lower than its deep learning-based counterparts.

The traditional method for analyzing the mechanism of stator winding inter turn short-circuit faults of synchronous condensers usually assumes that the stator current of the motor is close to three-phase symmetry, and based on this, a mathematical representation of the fault current of synchronous condensers is established. However, once a stator winding inter turn short-circuit fault occurs, the symmetry of the three-phase stator current of the synchronous condenser will be disrupted, making the mathematical representation established by traditional fault mechanism analysis methods unable to accurately reflect the changes in the internal electrical quantities of the motor. A mathematical model is established for the instantaneous active and reactive power of a synchronous condenser after a fault by introducing the symmetrical component method. Using the second harmonic in the instantaneous active and reactive power for stator winding inter turn short-circuit fault diagnosis is proposed. The simulation and experimental results indicate that compared to the traditional method of diagnosing faults using the ratio of the third harmonic of stator current to the amplitude of the fundamental wave, the proposed method can improve the diagnostic sensitivity by at least seven times under mild fault conditions, making it easy to complete early fault diagnosis. At the same time, the fault feature quantities in the proposed method are not affected by the synchronous condenser operating conditions and fault locations, and also have strong robustness.

Abstract Background The Citrus reticulata Blanco peels have been widely adopted as functional food or nutraceuticals for thousands of years. In our study, two polysaccharides from the C. reticulata Blanco peels were obtained and named as CRP-WA and CRP-02A, respectively. After characterization by monosaccharide composition, methylation and NMR, chemical structures of CRP-WA and CRP-02A were elucidated. Results As a result, CRP-WA with Mw of 32.8 kDa was an arabinogalactan polysaccharide composed of (β1 → 3) (β1 → 3,6)-D-Galp, (β1 → 4)-D-Manp and (β1 → 4)-D-Glcp units in the backbone. The CRP-02A with Mw of 70.5 kDa was an arabinogalacturonan type pectin formed by (α1 → 4) (α1 → 3,4)-D-GalpA units in the backbone. Moreover, the surface morphologies and rheological properties of CRP-WA and CRP-02A were quite different from each other. Both of these two polysaccharides possessed good antioxidant activities and immunoregulatory effects on RAW 264.7 cells, in which CRP-02A behaved remarkable antioxidant feature, whereas CRP-WA showed relatively high immunoregulatory activity. Conclusion Our study will provide fundamental information for C. reticulata Blanco-based nutritional foods development. Graphical Abstract

Abstract Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine metabolic disorders. The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) reportedly can regulate the reproductive system. Despite studies, the alteration of MALAT1 expression in granulosa cells (GCs) from PCOS patients was inconsistent. To evaluate MALAT1 expression in GCs in different PCOS subgroups and its association with PCOS phenotypes, we collected GCs from 110 PCOS cases and 71 controls, and examined MALAT1 expression by quantitative PCR. The results showed MALAT1 expression was upregulated in PCOS cases, especially in insulin resistant (IR) PCOS subgroup, obese PCOS subgroup and non-hyperandrogenic (NHA) PCOS subgroup. MALAT1 expression was positively correlated with BMI and several metabolic parameters in controls. Interestingly, MALAT1 expression was notably associated with some critical endocrine indexes for PCOS, including E2, FSH, LH and LH/FSH ratio. In different PCOS subgroups, we found significant positive correlations with LH/FSH ratio in IR-PCOS and PCOS with normal weight, and with serum T and LH level in NHA-PCOS subgroup. Integrated analysis with lncRNA target databases and PCOS-related databases revealed MALAT1 could participate in PCOS by influencing immune response and lipids metabolism in GCs. In conclusion, MALAT1 was differently expressed in GCs in PCOS, especially in IR, obese and NHA PCOS subgroups. MALAT1 was likely involved in metabolism and immune response in GCs in PCOS. However, more studies are necessary to establish this concept.

Abstract Currently, the classification of bone mineral density (BMD) in many research studies remains rather broad, often neglecting localized changes in BMD. This study aims to explore the correlation between peri-implant BMD and primary implant stability using a new artificial intelligence (AI)-based BMD grading system. 49 patients who received dental implant treatment at the Affiliated Hospital of Stomatology of Fujian Medical University were included. Recorded the implant stability quotient (ISQ) after implantation and the insertion torque value (ITV). A new AI-based BMD grading system was used to obtain the distribution of BMD in implant site, and the bone mineral density coefficients (BMDC) of the coronal, middle, apical, and total of the 1 mm site outside the implant were calculated by model overlap and image overlap technology. Our objective was to investigate the relationship between primary implant stability and BMDC values obtained from the new AI-based BMD grading system. There was a significant positive correlation between BMDC and ISQ value in the coronal, middle, and total of the implant (P 0.05). Furthermore, BMDC was notably higher at implant sites with greater ITV (P