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Interoception, the sense of the physiological condition of our body, is impaired in individuals with autism spectrum disorders. Evidence suggests that subclinical autistic traits are mild manifestations of autistic symptoms, present in the general population. We examined the resting-state functional connectivity (rsFC) associating with interoception and autistic traits in 62 healthy young adults. Autistic traits correlated negatively with the rsFC between the lateral ventral anterior insula and anterior cingulate cortex. Interoceptive accuracy and sensibility correlated positively with the rsFC between interoceptive brain networks and the cerebellum, supplementary motor area, and visual regions. The results suggest that a negative relationship between interoception and autistic traits is largely accounted for by both self-report measures and decreased rsFC amongst the interoceptive brain network.

Background: Investigating emotion sequence patterns in the posts of discussion forums in massive open online courses (MOOCs) holds a vital role in shaping online interactions and impacting learning achievement. While the majority of research focuses on the relationship between emotions and interactions in MOOC forum discussions, research on identifying the crucial difference in emotion sequence patterns among different interaction groups remains in its infancy. Objectives: This research utilizes deep learning and sequential pattern mining to investigate whether there are differences in emotion sequence patterns across different groups of learners who exhibit various types of interactions in online discussion forums. Methods: Data from a comprehensive array of sources, including log files, discussion texts and scores from 498 learners in online discussion forums, were collected for this study. The agglomerative hierarchical algorithm is used to classify learners into groups with different levels of interactions. Additionally, we implement and evaluate multiple deep learning models for detecting different emotions from online discussions. Relevant emotion sequence patterns were identified using sequence pattern analysis and the identified emotion sequence patterns were compared across different groups with different levels of interactions. Results and Conclusions: Using an agglomerative hierarchical algorithm, we classified learners into three distinct groups characterized by different levels of interactions: high, average and low level. Leveraging the bi-directional long short-term memory model for emotion detection yielded the highest predictive performance, with an impressive F-measure of 94.01%, a recall rate of 93.83% and an accuracy score of 95.01%. The results also revealed that learners in the low-level interaction group experienced more emotion transition from boredom to frustration than the other two groups. Therefore, the aggregation of students into groups and the utilization of their MOOC log data offer educators the capability to provide adaptive emotional feedback, customize assessments and offer more personalized attention as needed.

In present study, the mitogenome of Rosa laevigata was assembled and characterized, with a total length of 281,693 bp and a GC content of 45.4%. The genome encompasses 53 genes, including 32 protein-coding genes, 3 rRNA genes and 18 tRNA genes. Furthermore, 19 MTPTs were identified, ranging from 48 to 1585 bp, covering 3.1% (8764 bp) of the mitogenome. Phylogenetic analysis of 34 Rosaceae species based on 21 common conserved protein-coding genes detected the monophyly of Rosa, with R. laevigata and R. chinensis forming a sister clade to R. rugosa. The mitogenome provides valuable genetic resources for R. laevigata utilization and for further phylogeny reconstruction of Rosa and Rosaceae.

Semen Lepidii is the dried and mature seeds of the cruciferous plant of Descurainia Sophia or Lepidium Apetalum, being a widely-used traditional Chinese medicine for various pharmacological effects, such as antibacterial, antitumor, diuretic and improving immune function. However, the chemical components of Semen Ledidii from different regions have not been clear, limiting the further application of this herb medicine in clinic. Therefore, in this study, a method of ultra-performance liquid chromatography-electrostatic Orbital ion trap tandem mass spectrometry (UPLC-Orbitrap-MS/MS) was developed to identify the chemical components of the three Semen Lepidii, namely Descurainia Sophia 1 (DS1), Descurainia Sophia 2 (DS2) and Lepidium Apetalum (LA) from different regions, and to study the fragmentation pathways of the identified components. The methanol-water (70:30, V/V) extract of the three mashed powder samples was separated on an ACQUITY UPLC BEH C18 column (100 mm×2.1 mm×1.7 μm), and infused into high mass resolution Orbitrap mass spectrometer for analyzing under positive and negative ion modes. MS/MS data were acquired with a Full MS/dd-MS2 mode, and the chromatographic peaks were aligned and extracted by using Compound Discoverer (CD) software. Then, the accurate mass informations of the precursor and fragment ions were matched to the databases in the CD platform for identification of components in the samples, and studied the fragmentation pathways of identified compounds. A total of 39 compounds are identified in DS1, including alkaloids, flavonoids, cardiac glycosides, amides, organic acids, amino acids, and others. This method was used to analyze methanol-water extract of DS2 and LA, 37 compounds are identified in DS2, including 10 compounds which are not identified in DS1, and 42 compounds are identified in LA, including 7 compounds which are not identified in both DS1 and DS2. The results indicated that the chemical components of Semen Lepidii originated from different regions are remarkably different and may act as medicine in various ways. This study provides a fundamental for further studying the molecular mechanism of pharmacological effects of Semen Lepdii, which can promote its clinical application.

Abstract Conventional methods for identifying voltage sag sources are difficult to categorize accurately due to the complexity of transmission lines and the influence of noise. In order to solve the problem of difficulty in recognizing voltage sag sources of transmission lines under different locations, this paper proposes a new method for transmission line fault diagnosis based on modified wavelet denoising and multi‐location information convolution transformer. The improved wavelet denoising method proposed in this paper solves the problems of discontinuity and bias of the traditional wavelet denoising method, and is able to better reconstruct the original voltage signal in a strong noise environment. In addition, multi‐location information convolution transformer adopts a new model combining multi‐location information convolution and multi‐scale convolution transformer, which realizes the combination of global information and local context information capturing ability under multi‐location faults. This paper validates the method through simulation experiments and practical situations, and the results show that the method can well classify and identify the type and location of voltage sag sources in transmission lines.

A novel genus, Paradingleyomyces was introduced to accommodate Pa. lepidopterorum sp. nov., based on a multigene phylogenetic analysis and its distinct morphological characteristics. Maximum likelihood (ML) and Bayesian inference analyses (BI) of ITS, SSU, LSU, tef-1α, rpb1, and rpb2 sequence data shown that Pa. lepidopterorum formed an independent lineage nested between Perennicordyceps and Dingleyomyces. Morphologically, Paradingleyomyces is distinguished from Perennicordyceps by the presence of a white subiculum on the stromata of Ophiocordyceps cf. cochlidiicola. Perithecia are produced sporadically from the base to the apex of the stromata, and the secondary ascospores exhibit a notable length-to-width ratio. These characteristics distinguish Paradingleyomyces from Perennicordyceps which exhibits tortuous, branched, clavate to cylindrical stromata with rhizomorphs, parasitism of coleopteran and hemipteran larvae, and colonizes a broader range of fungal hosts. Additionally, perithecia in Perennicordyceps typically arise from the middle to the upper regions of the stromata, with secondary ascospores displaying a comparatively lower length-to-width ratio. Paradingleyomyces is morphologically identical to Dingleyomyces in its direct production of superficial perithecia on the stromata of Ophiocordyceps species. However, the phylogenetic analysis indicates that Paradingleyomyces and Dingleyomyces are not congeneric. Moreover, this study introduces another novel species, Polycephalomyces tengchongensis, and a novel sexual morph of Pleurocordyceps yunnanensis. Dimorphic phialides and conidia of Pleurocordyceps parvicapitata were observed and described for the first time based on a fresh collection from Tengchong County, Yunnan Province, China.

Abstract The fundamental leucine zipper (bZIP) genes play a crucial role as transcriptional coactivators in plants. Pseudoroegneria libanotica served as the maternal contributor to several species within the tribe Triticeae (Poaceae), exhibiting commendable resilience to various stressors. Consequently, bZIP genes of Pseudoroegneria libanotica response to abiotic stresses was important for further understanding of stress tolerance studies in Triticeae. A total of 108 PsebZIPs were identified in this study, and they were divided into 10 subgroups. PsebZIPs were found to be extensively involved in the biological activities within P. libanotica. The RNA-seq results revealed differential responses of PsebZIPs to drought stress in both aerial and root tissues. PsebZIP44 and PsebZIP46 were regarded as potential genes capable of responding to abiotic stress, and their varying degrees of responsiveness to drought, salinity, heavy metals, heat, and oxidative stress have been demonstrated in yeast. Homologous proteins with intact bZIP gene structures of PsebZIP44 or PsebZIP46 have not been identified in wheat. The current investigation not only provides a fundamental basis for further probing into the biological functions of PsebZIPs within P. libanotica but also reveals previously undiscovered potential genes with the ability to respond to abiotic stress. They could contribute to improving the genetic constitution of Triticeae crops, including wheat.

Abstract Transthoracic echocardiography (TTE) is widely recognized as one of the principal modalities for diagnosing tricuspid regurgitation (TR). The diagnostic procedures associated with conventional methods are intricate and labor-intensive, with human errors leading to measurement variability, with outcomes critically dependent on the operators’ diagnostic expertise. In this study, we present an innovative assessment methodology for evaluating TR severity utilizing an end-to-end deep learning system. This deep learning system comprises a segmentation model of single cardiac cycle TR continuous wave (CW) Doppler spectra and a classification model of the spectra, trained on the TR CW Doppler spectra from a cohort of 11,654 patients. The efficacy of this intelligent assessment methodology was validated on 1500 internal cases and 573 external cases. The receiver operating characteristic (ROC) curves of the internal validation results indicate that the deep learning system achieved the areas under curve (AUCs) of 0.88, 0.84, and 0.89 for mild, moderate, and severe TR, respectively. The ROC curves of the external validation results demonstrate that the system attained the AUCs of 0.86, 0.79, and 0.87 for mild, moderate, and severe TR, respectively. Our study results confirm the feasibility and efficacy of this novel intelligent assessment method for TR severity.

Abstract Background Endometriosis (EMS) and chronic endometritis (CE) frequently coexist. This study aimed to examine the impact of CE on reproductive outcomes in patients with EMS. Methods We enrolled 685 patients with endometriosis-associated infertility from January 2018 to December 2020. The patients were divided into CE (318) and non-CE (367) groups. A subset of 123 clinically pregnant women from the CE group and 369 from the non-CE group was selected for detailed comparison. Pregnancy and delivery data were meticulously collected from hospital records and through telephone interviews. Results CE was diagnosed in 46.42% of EMS patients. Higher pregnancy rates were observed in patients with Endometriosis Fertility Index (EFI) scores of 7–10. EMS patients with CE had increased risks of placenta previa (13.01%), gestational hypertension (5.69%), and cesarean sections (59.34%). Conclusions CE, which is prevalent among EMS patients, is linked to increased risks of pregnancy complications, including placenta previa, gestational hypertension, and cesarean delivery. Although combined hysteroscopy and laparoscopy improve pregnancy rates, they demand careful management of these complications.

Abstract Objectives This study aimed to develop and validate a deep-learning radiomics model using CT, T2, and DWI images for predicting pathological complete response (pCR) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT). Materials and methods Patients with ESCC undergoing nCRT followed by surgery were retrospectively enrolled from three institutions and divided into training and testing cohorts. Both traditional and deep-learning radiomics features were extracted from pre-treatment CT, T2, and DWI. Multiple radiomics models were developed, both single modality and integrated, using machine learning algorithms. The models’ performance was assessed using receiver operating characteristic curve analysis, with the area under the curve (AUC) as a primary metric, alongside sensitivity and specificity from the cut-off analysis. Results The study involved 151 patients, among whom 63 achieved pCR. The training cohort consisted of 89 patients from Institution 1 (median age 62, 73 males) and the testing cohort included 52 patients from Institution 2 (median age 62, 41 males), and 10 in a clinical trial from Institution 3 (median age 69, 9 males). The integrated model, combining traditional and deep learning radiomics features from CT, T2, and DWI, demonstrated the best performance with an AUC of 0.868 (95% CI: 0.766–0.959), sensitivity of 88% (95% CI: 73.9–100), and specificity of 78.4% (95% CI: 63.6–90.2) in the testing cohort. This model outperformed single-modality models and the clinical model. Conclusion A multimodality deep learning radiomics model, utilizing CT, T2, and DWI images, was developed and validated for accurately predicting pCR of ESCC following nCRT. Critical relevance statement Our research demonstrates the satisfactory predictive value of multimodality deep learning radiomics for the response of nCRT in ESCC and provides a potentially helpful tool for personalized treatment including organ preservation strategy. Key Points After neoadjuvant chemoradiotherapy, patients with ESCC have pCR rates of about 40%. The multimodality deep learning radiomics model, could predict pCR after nCRT with high accuracy. The multimodality radiomics can be helpful in personalized treatment of esophageal cancer. Graphical Abstract

Abstract The locomotive action involves diverse coordination, necessitating the integration of multiple motor neural circuits. However, the precise circuitry mechanism governing emotion-driven accelerated locomotion remains predominantly elusive. Here we dissect projections from the tuberomammillary nucleus (TMN) to subiculum (SUB) which promote alert-driven accelerated locomotion. We find that TMN histaminergic neurons respond to high-speed locomotion in both natural and alert acceleration. The TMN-SUB circuit is sufficient but not essential for amplifying accelerated locomotion from low to high-speed movement in basal condition, but it is both sufficient and necessary in alert condition for modulating accelerated locomotion during high-speed escape behavior. TMN histaminergic neuron activates SUB glutamatergic “fast locomotor cell” that projects to retrosplenial granular cortex (RSG) mainly through histamine H2 receptor (H2R). This study reveals the critical role of the histamine-tuned SUB circuit in alert-driven accelerated locomotion in mice, providing a theoretical foundation for comprehending neural circuit mechanisms of instinctive behaviors under alert.

Abstract In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge in interest can be largely attributed to the demonstration of distinct advantages offered by various mRNA molecules, alongside the rapid advancements in nucleic acid delivery systems. It is noteworthy that the immunogenicity of mRNA drugs presents a double-edged sword. In the context of immunotherapy, extra supplementation of adjuvant is generally required for induction of robust immune responses. Conversely, in non-immunotherapeutic scenarios, immune activation is unwanted considering the host tolerability and high expression demand for mRNA-encoded functional proteins. Herein, mainly focused on the linear non-replicating mRNA, we overview the preclinical and clinical progress and prospects of mRNA medicines encompassing vaccines and other therapeutics. We also highlight the importance of focusing on the host-specific variations, including age, gender, pathological condition, and concurrent medication of individual patient, for maximized efficacy and safety upon mRNA administration. Furthermore, we deliberate on the potential challenges that mRNA drugs may encounter in the realm of disease treatment, the current endeavors of improvement, as well as the application prospects for future advancements. Overall, this review aims to present a comprehensive understanding of mRNA-based therapies while illuminating the prospective development and clinical application of mRNA drugs.

Abstract Using e + e − collision data collected by the BESIII detector at BEPCII corresponding to an integrated luminosity of 30 fb −1, we measure Born cross sections and effective form factors for the process e + e − → Ξ 0 Ξ ¯ 0 $$ {e}^{+}{e}^{-}\to {\Xi}^0{\overline{\Xi}}^0 $$ at forty-five center-of-mass energies between 3.51 and 4.95 GeV. The dressed cross section is fitted, assuming a power-law function plus a charmonium(-like) state, i.e., ψ(3770), ψ(4040), ψ(4160), ψ(4230), ψ(4360), ψ(4415) or ψ(4660). No significant charmonium(-like) state decaying into Ξ 0 Ξ ¯ 0 $$ {\Xi}^0{\overline{\Xi}}^0 $$ is observed. Upper limits at the 90% confidence level on the product of the branching fraction and the electronic partial width are provided for each decay. In addition, ratios of the Born cross sections and the effective form factors for e + e − → Ξ 0 Ξ ¯ 0 $$ {e}^{+}{e}^{-}\to {\Xi}^0{\overline{\Xi}}^0 $$ and e + e − → Ξ − Ξ ¯ + $$ {e}^{+}{e}^{-}\to {\Xi}^{-}{\overline{\Xi}}^{+} $$ are also presented to test isospin symmetry and the vector meson dominance model.

Abstract Objectives Viral hepatitis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain a major global public health challenge, particularly in low- and middle-income countries. It is crucial to utilize a pointof-care (POC) testing platform that is sensitive, specific, rapid, and user-friendly for screening and diagnosis of the two infections. Here, a novel molecular diagnostic assay, integrating multiplex loop-mediated isothermal amplification with a gold nanoparticle-based lateral flow biosensor (mLAMP-AuNPs-LFB) was developed and applied for one-step, visual, rapid, sensitive, and specific identification of HBV and HCV. Methods The AuNPs-based LFB was devised and constructed for the simultaneous detection of HBV and HCV. The HBV-LAMP and HCV-LAMP primers were designed against the S and 5′-untranslated region (5′-UTR) genes from the major HBV genotypes (B, C, D, B/C recombinant, and C/D recombinant) and HCV subtypes (1b, 2a, 3a, 3b, and 6a) in China, respectively. Our assay conditions, both multiplex-LAMP amplification temperature and time were optimized. The sensitivity and specificity of our assay were tested, and the feasibility of our assay was verified through clinical samples. Results The AuNPs-based LFB used here was successfully manufactured according to our devise manual. The two unique independent primer pairs were successfully designed based on the S and 5′-UTR genes, respectively. The optimal mLAMP-AuNPs-LFB detection process, involving rapid nucleic acid isolation (10 min), mLAMP (63 °C for 35 min), and visual AuNPs-LFB interpretation (less than 2 min), could be completed within 50 min. The HBV&HCV-mLAMP-AuNPs-LFB assay can detect the target genes (HBV-S and HCV-5′-UTR) with as low as 20 copies of plasmid template per test, and the specificity was 100% for the experimental pathogens. Conclusions The preliminary results manifested that our mLAMP-AuNPs-LFB assay is a valuable tool and has tremendous potential as a POC testing approach for HBV and HCV identification, especially in undeveloped regions.

Abstract This study aimed to observe the characteristics of foot posture asymmetry and abnormal gait in patients with unilateral and bilateral knee osteoarthritis (KOA) and to explore the association between foot posture asymmetry, abnormal gait and the clinical symptoms and severity of KOA. Sixty patients with KOA were allocated as follows: unilateral group (UG; n = 30) and bilateral group (BG; n = 30). We accessed foot posture, foot posture asymmetry, gait and plantar pressure parameters and symmetry index, clinical symptom-related scores and disease severity, and investigated the relationship between these variables. The results showed that the overall percentage of asymmetry and severe asymmetry in foot posture were lower in BG than in UG. There was substantial asymmetry in many gait indicators within the two groups, but no significant differences were observed between the two groups. Moreover, foot posture asymmetry, multiple gait and plantar pressure parameters and symmetry indices were closely related to clinical symptoms and disease severity. In conclusion, both unilateral and bilateral KOA patients have foot posture asymmetry and gait asymmetry, but the foot posture asymmetry of the former is more severe than that of the latter. Intervention for this population should treat simultaneously both knee joints. The evaluation and monitoring of foot posture asymmetry, gait and plantar pressure parameters and symmetry indices can provide a more comprehensive and scientific basis for the prevention and treatment of KOA.

Osteoporosis is a chronic metabolic disease that increases bone fragility and, leads to severe osteoporotic fractures. In recent years, the use of high-throughput omics to explore physiological and pathological biomarkers related to bone metabolism has gained popularity. In this review, we first briefly review the technical approaches of proteomics. Additionally, we summarize the relevant literature in the last decade to provide a comprehensive overview of advances in human proteomics related to osteoporosis. We describe the specific roles of various proteins related to human bone metabolism, highlighting their potential as biomarkers for risk assessment, early diagnosis and disease course monitoring in osteoporosis. Finally, we outline the main challenges currently faced by human proteomics in the field of osteoporosis and offer suggestions to address these challenges, to inspire the search for novel osteoporosis biomarkers and a foundation for their clinical translation. In conclusion, proteomics is a powerful tool for discovering osteoporosis-related biomarkers, which can not only provide risk assessment, early diagnosis and disease course monitoring, but also reveal the underlying mechanisms of disease and provide key information for personalized treatment. The translational potential of this article: This review provides an insightful summary of recent human-based studies on osteoporosis-associated proteomics, which can aid the search for novel osteoporosis biomarkers based on human proteomics and the clinical translation of research results.

This study introduces a pioneering design concept termed the “dual-feedback healing mechanism”, which investigates the relationship between oxidation products and protective coatings. Specifically, it focuses on channeling oxidation products generated at exposed cracks in the substrate to interact with the antioxidant coatings, enabling a self-repair mechanism for cracks. BNf/SiBN was chosen as the ceramic matrix, while the Si‒O‒Al system served as the antioxidant coating. The dynamic process of obtaining Si–O–Al (SOAC) coating involving the pyrolysis of organic precursors and the dual-feedback healing mechanism were systematically investigated. These findings indicate that when the temperature surpasses 1150 °C, the exposed BN fibers at the cracks are oxidized, transforming into B2O3(g). Subsequently, B2O3(g) reacts with SiO2, forming a SiBO mixture. The mixture effectively diminishes the viscosity of the coating, enabling it to flow and form a fresh protective layer that effectively blocks O2 infiltration. Consequently, after oxidation at 1500 °C, the coated samples experience a mere 3% weight loss. This technology emphasizes the interconnectivity during material transformation, utilizing matrix oxidation products as a driving force for self-healing of the coating. This approach achieves intelligent-like, targeted closure of oxygen pathways, thereby pioneering a novel concept and direction for the advancement of antioxidant coatings. Consequently, this approach not only enhances our understanding of the fundamental nature of “self-healing” but also holds significant potential in the development of reparable antioxidant coatings.

Abstract The branching fraction of D + → K S 0 π 0 e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^0{e}^{+}{\nu}_e $$ is measured for the first time using 7.93 fb −1 of e + e − annihilation data collected at the center-of-mass energy s $$ \sqrt{s} $$ = 3.773 GeV with the BESIII detector operating at the BEPCII collider, and is determined to be B D + → K S 0 π 0 e + ν e = 0.881 ± 0.017 stat . ± 0.016 syst . % $$ \mathcal{B}\left({D}^{+}\to {K}_S^0{\pi}^0{e}^{+}{\nu}_e\right)=\left(0.881\pm {0.017}_{\textrm{stat}.}\pm {0.016}_{\textrm{syst}.}\right)\% $$ . Based on an analysis of the D + → K S 0 π 0 e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^0{e}^{+}{\nu}_e $$ decay dynamics, we observe the S-wave and P-wave components with fractions of f S-wave = (6.13 ± 0.27stat. ± 0.30syst. )% and f K ¯ ∗ 892 0 = 93.88 ± 0.27 stat . ± 0.29 syst . % $$ {f}_{{\overline{K}}^{\ast }{(892)}^0}=\left(93.88\pm {0.27}_{\textrm{stat}.}\pm {0.29}_{\textrm{syst}.}\right)\% $$ , respectively. From these results, we obtain the branching fractions B D + → K S 0 π 0 S − wave e + ν e = 5.41 ± 0.35 stat . ± 0.37 syst . × 10 − 4 $$ \mathcal{B}\left({D}^{+}\to {\left({K}_S^0{\pi}^0\right)}_{S-\textrm{wave}}{e}^{+}{\nu}_e\right)=\left(5.41\pm {0.35}_{\textrm{stat}.}\pm {0.37}_{\textrm{syst}.}\right)\times {10}^{-4} $$ and B D + → K ¯ ∗ 892 0 e + ν e = 4.97 ± 0.11 stat . ± 0.12 syst . % $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}^{\ast }{(892)}^0{e}^{+}{\nu}_e\right)=\left(4.97\pm {0.11}_{\textrm{stat}.}\pm {0.12}_{\textrm{syst}.}\right)\% $$ . In addition, the hadronic form-factor ratios of D + → K ¯ ∗ 892 0 e + ν e $$ {D}^{+}\to {\overline{K}}^{\ast }{(892)}^0{e}^{+}{\nu}_e $$ at q 2 = 0, assuming a single-pole dominance parameterization, are determined to be r V = V 0 A 1 0 = 1.43 ± 0.07 stat . ± 0.03 syst . $$ {r}_V=\frac{V(0)}{A_1(0)}=1.43\pm {0.07}_{\textrm{stat}.}\pm {0.03}_{\textrm{syst}.} $$ and r 2 = A 2 0 A 1 0 = 0.72 ± 0.06 stat . ± 0.02 syst . $$ {r}_2=\frac{A_2(0)}{A_1(0)}=0.72\pm {0.06}_{\textrm{stat}.}\pm {0.02}_{\textrm{syst}.} $$ .

Abstract Chimeric Antigen Receptor T (CAR-T) cell therapy has significantly advanced in treating B-cell acute lymphoblastic leukemia (B-ALL) and has shown efficacy in managing relapsed B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor-derived CAR-T cell offer both high efficacy and rapid response. Although promising results exist, current research lacks definitive evidence of long-term survival benefits for patients treated with donor-derived CAR-T therapy. We report the long-term survival of 32 patients with post-transplant relapsed B-ALL treated with donor-derived CD19 CAR-T cell, achieving either complete Remission (CR) or CR with incomplete peripheral blood recovery (CRi). The median follow-up was 42 months, with 2-year overall survival (OS) and event-free survival (EFS) rates of 56.25% and 50.0%, respectively. The 5-year OS and EFS rates were 53.13% and 46.88%, with no new long-term adverse events observed. These findings demonstrate good long-term safety, supporting donor-derived CAR-T cell as a recommended treatment option for relapsed B-ALL patients post-transplantation. Trial registration: https://www.chictr.org.cn/showproj.html?proj=14315 . Registration number: ChiCTR-OOC-16008447.

Abstract Atherosclerosis (AS) poses a significant threat to human life and health. However, conventional antiatherogenic medications exhibit insufficient targeting precision and restricted therapeutic effectiveness. Moreover, during the progression of AS, macrophages undergo polarization toward the proinflammatory M1 phenotype and generate reactive oxygen species (ROS) to accelerate the occurrence of inflammatory storms, and ingest excess lipids to form foam cells by inhibiting cholesterol efflux. In our study, we developed a macrophage membrane-functionalized hollow mesoporous manganese dioxide nanomedicine (Col@HMnO2-MM). This nanomedicine has the ability to evade immune cell phagocytosis, enables prolonged circulation within the body, targets the inflammatory site of AS for effective drug release, and alleviates the inflammatory storm at the AS site by eliminating ROS. Furthermore, Col@HMnO2-MM has the ability to generate oxygen autonomously by breaking down surplus hydrogen peroxide generated at the inflammatory AS site, thereby reducing the hypoxic microenvironment of the plaque by downregulating hypoxia-inducible factor (HIF-1α), which in turn enhances cholesterol efflux to inhibit foam cell formation. In an APOE−/− mouse model, Col@HMnO2-MM significantly reduced inflammatory factor levels, lipid storage, and plaque formation without significant long-term toxicity. In summary, this synergistic treatment significantly improved the effectiveness of nanomedicine and may offer a novel strategy for precise AS therapy.

With the increase in the proportion of renewable energy connected to the grid, a large number of N-1 security constraints should be considered in the security-constrained economic dispatch (SCED) to ensure the reliable operation of the power system, which causes a great computational burden. However, only a small number of constraints in the N-1 security constraints are contributing factors. Therefore, the elimination of redundant constraints can significantly improve the solution efficiency of the SCED model. First, a new SCED model considering wind power and photovoltaic is established, and a low-rank approximation (LRA) surrogate model is constructed based on the historical operation information of the SCED model. Then, the active constraints are identified based on the estimation results of the LRA surrogate model and the active constraint set is constructed. Next, an iterative solution process of the SCED model based on LRA surrogate model is proposed. Finally, the simulations are conducted on an IEEE 39-bus system. The simulation results show that the error between the solution results of the LRA surrogate and the SCED models is less than 10%, the active constraint identification accuracy is raised, and the average iterative solution time of the proposed solution process is reduced by more than 50%, which indicates the improvement of the solution efficiency of the SCED model.

Abstract In this study, nonaxisymmetric endwall contouring technology is employed as a passive control strategy to enhance the stable operating range of a centrifugal compressor with an asymmetric volute. The endwall contouring method is applied to the hub‐side wall of the vaned diffuser within a centrifugal compressor stage. Instead of utilizing a flat hub as the baseline diffuser, various diffuser configurations featuring hub‐side contoured endwalls are explored, with adjustments in the peak radial position and peak height of the convex and concave profiles. Numerical simulations are conducted to evaluate the performance of the centrifugal compressor stage with both the baseline and contoured vaned diffusers. The investigation explores the underlying flow control mechanisms and establishes the effective endwall contouring guidelines. The findings highlight the effectiveness of endwall contouring in enhancing the stable operating range of centrifugal compressors. Notably, a substantial enhancement of 15.1% in the stable operating range is achieved by employing the contoured diffuser with the peak radial position near the vane leading edge (LE) and the peak height at 20% of the vane height. The endwall contoured diffusers reduce the positive LE incidence angles to direct the fluid toward the suction side (SS), and increase the radial velocity near the SS to suppress the hub‐suction corner separations in the diffuser passages near the volute tongue. These improvements collectively contribute to the enhancement of diffuser flow characteristics. Finally, a set of effective endwall contouring guidelines is proposed to guide the endwall contouring design for enhancing the stable operating range of centrifugal compressors.

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic lung disease with limited treatment options and efficacy. Evidence suggests that IPF arises from genetic, environmental, and aging-related factors. The pathogenic mechanisms of IPF primarily involve dysregulated repeated microinjuries to epithelial cells, abnormal fibroblast/myofibroblast activation, and extracellular matrix (ECM) deposition, but thus far, the exact etiology remains unclear. Noncoding RNAs (ncRNAs) play regulatory roles in various biological processes and have been implicated in the pathophysiology of multiple fibrotic diseases, including IPF. This review summarizes the roles of ncRNAs in the pathogenesis of IPF and their potential as diagnostic and therapeutic targets.

Abstract Background Fusarium head blight (FHB), a devastating disease of wheat production, is predominantly elicited by Fusarium graminearum (Fg). The tetraploid Thinopyrum elongatum is a tertiary gene resource of common wheat that possesses high affinity and displays high resistance traits against multiple biotic and abiotic stress. We aim to employ and utilize the novel FHB resistance resources from the wild germplasm of common wheat for breeding. Results Durum wheat-tetraploid Th. elongatum amphiploid 8801 was hybridized with common wheat cultivars SM482 and SM51, and the F5 generation was generated. We conducted cytogenetically in situ hybridization (ISH) technologies to select and confirm a genetically stable 7E(7D) substitution line K17-1069-5, which showed FHB expansion resistance in both field and greenhouse infection experiments and displayed no significant disadvantage in agronomic traits compared to their common wheat parents in the field. The F2 segregation populations (K17-1069-5 × SM830) showed that the 7E chromosome conferred dominant FHB resistance with dosage effect. We developed 19 SSR molecular markers specific to chromosome 7E, which could be conducted for genetic mapping and large breeding populations marker-assisted selection (MAS) during selection procedures in the future. We isolated a novel Fhb7 allele from the tetraploid Th. elongatum chromosome 7E (Chr7E) using homology-based cloning, which was designated as TTE7E-Fhb7. Conclusions In summary, our study developed a novel wheat-tetraploid Thinopyrum elongatum 7E(7D) K17-1069-5 substitution line which contains stable FHB resistance.

Abstract Expiratory CO2 concentrations can directly reflect human physiological conditions, and their detection is highly important in the treatment and rehabilitation of critically ill patients. Existing respiratory gas analyzers suffer from large sizes and high power consumption due to the limitations of the internal CO2 sensors, which prevent them from being wearable to track active people. The internal and external interference and sensitivity limitations must be overcome to realize wearable respiratory monitoring applications for CO2 sensors. In this work, an ultra-compact CO2 sensor was developed by integrating a microelectromechanical system emitter and thermopile detectors with an optical gas chamber; the power consumption of the light source and ambient temperature of the thermally sensitive devices were reduced by heat transfer control; the time to reach stabilization of the sensor was shortened; the humidity resistance of the sensor was improved by a dual-channel design; the light loss of the sensor was compensated by improving the optical coupling efficiency, which was combined with the amplitude trimming network to equivalently improve the sensitivity of the sensor. The minimum size of the developed sensor was 12 mm × 6 mm × 4 mm, and the reading error was

The direct one-step separation of polymer-grade C2H4 from complex light hydrocarbon mixtures has high industrial significance but is very challenging. Herein, an ethylene-adsorption-weakening strategy is applied for precise regulation of the pore geometry of four tailor-made metal–organic frameworks (MOFs) with pillar-layered structures, dubbed TYUT-10/11/12/13. Based on its pore geometry design and functional group regulation, TYUT-12 exhibits exceptional selective adsorption selectivity toward C3H8, C3H6, C2H6, C2H2, and CO2 over C2H4; its C2H6/C2H4 adsorption selectivity reaches 4.56, surpassing the record value of 4.4 by Fe2(O2)(dobdc) (dobdc4− = 2,5-dioxido-1,4-benzenedicarboxylate). The weak π–π stacking binding affinity toward C2H4 in TYUT-12 is clearly demonstrated through a combination of neutron powder diffraction measurements and theoretical calculations. Breakthrough experiments demonstrate that C2H4 can be directly obtained from binary, ternary, quaternary, and six-component light hydrocarbon mixtures with over 99.95% purity.

Abstract Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs), possess immunomodulatory properties and have shown promising outcomes when combined with anti-PD-1 antibodies. The OASIS phase II trial (NCT04503967) is designed to determine the clinical activity and safety of nivolumab (anti-PD-1) and anlotinib hydrochloride (a multi-targets TKI) as second-line or above therapy in patients with advanced gastric adenocarcinoma (GAC) and esophageal squamous cell carcinoma (ESCC). From December 2020 to September 2022, 45 patients with GAC and 3 with ESCC were enrolled in this study. The pre-specified endpoints were reached, with the primary endpoint of overall response rate achieving 29.2%. For secondary objectives, disease control rate was 64.6%; median progression-free survival was 4.0 months; and median overall survival was 11.1 months with a manageable toxicity profile. The exploratory analyses unveiled that the balance of gut bacteria and the presence of a pre-existing immune signature characterized by a high percentage of CD68+PD-L1+ PD-1+ macrophages and low pretreatment variant allele frequencies (VAF), as well as low expression of certain cytokines were significantly associated with improved clinical outcomes in patients with GAC.

Abstract The ubiquitous smart meters are expected to be a central feature of future smart grids because they enable the collection of massive amounts of fine-grained consumption data to support demand-side flexibility. However, current smart meters are not smart enough. They can only perform basic data collection and communication functions and cannot carry out on-device intelligent data analytics due to hardware constraints in terms of memory, computation, and communication capacity. Moreover, privacy concerns have hindered the utilization of data from distributed smart meters. Here, we present an end-edge-cloud federated split learning framework to enable collaborative model training on resource-constrained smart meters with the assistance of edge and cloud servers in a resource-efficient and privacy-enhancing manner. The proposed method is validated on a hardware platform to conduct building and household load forecasting on smart meters that only have 192 KB of static random-access memory (SRAM). We show that the proposed method can reduce the memory footprint by 95.5%, the training time by 94.8%, and the communication burden by 50% under the distributed learning framework and can achieve comparable or superior forecasting accuracy to that of conventional methods trained on high-capacity servers.

Abstract The Riemerella anatipestifer bacterium is known to cause infectious serositis in ducklings. Moreover, its adherence to the host’s respiratory mucosa is a critical step in pathogenesis. Membrane cofactor protein (MCP; CD46) is a complement regulatory factor on the surface of eukaryotic cell membranes. Bacteria have been found to bind to this protein on host cells. Outer membrane proteins (OMPs) are necessary for adhesion, colonisation, and pathogenicity of Gram-negative bacteria; however, the mechanism by which R. anatipestifer adheres to duck cells remains unclear. In this study, pull-down assays and LC–MS/MS identified eleven OMPs interacting with duck CD46 (dCD46), with OMP71 exhibiting the strongest binding. The ability of an omp71 gene deletion strain to bind dCD46 is weaker than that of the wild-type strain, suggesting that this interaction is important. Further evidence of this interaction was obtained by synthesising OMP71 using an Escherichia coli recombinant protein expression system. Adhesion and invasion assays and protein and antibody blocking assays confirmed that OMP71 promoted the R. anatipestifer YM strain (RA-YM) adhesion to duck embryo fibroblasts (DEFs) by binding to CD46. Tests of the pathogenicity of a Δomp71 mutant strain of RA-YM on ducks compared to the wild-type parent supported the hypothesis that OMP71 was a key virulence factor of RA-YM. In summary, the finding that R. anatipestifer exploits CD46 to bind to host cells via OMP71 increases our understanding of the molecular mechanism of R. anatipestifer invasion. The finding suggests potential targets for preventing and treating diseases related to R. anatipestifer infection.

Abstract Excessive alarmins S100A8/A9 escalate the inflammation and even exacerbate immune-driven thrombosis and multi-organ damage. However, the regulatory mechanisms of S100A8/A9 expression in infectious diseases remain unclear. In this study, high-dimensional transcriptomic data analyses revealed a high proportion of CD14+FCN1hi macrophages within the pulmonary niche post-severe SARS-CoV-2 infection. By constructing the S100-coexpression gene list and supervised module scoring, we found that CD14+FCN1hi macrophages presented the highest scores of alarmin S100, and possibly served as the trigger and amplifier of inflammation in severe COVID-19. These CD14+FCN1hi cells lacked the positive regulatory activity of transcription factor PPARγ, and lost their differentiation ability towards mature macrophages. Ex vivo experiments further validated that the epithelial cells with high ORF-3a expression promoted the expression and secretion of S100A8/A9 through ANXA1/SAA1-FPR1 signaling. S100A8/A9 heterodimers, as well as the co-localization of S100A8/A9 with microtubules, were both diminished by the FPR1 inhibitor. Phospho-kinase protein array indicated that STAT3 promoted transcription, and PLC-γ and ERK1/2 pathways were involved in the hetero-dimerization and unconventional secretion of S100A8/A9. Our study highlights the pivotal role of FPR1 signaling in the excessive production of S100A8/A9 and provides a promising target for the prevention and control of severe COVID-19 and post-acute COVID-19 sequelae.

Abstract Background The prevalence of chronic conditions increases rapidly among older population. However, it is unclear how different chronic conditions progression contributes to the health care utilization, and whether intergenerational support modified this relationship. This study aimed to explore the longitudinal link between chronic condition progression and health care utilization, and examine whether intergenerational financial support is a moderator in this relationship among Chinese rural older people. Methods Data was derived from the Shandong Rural Elderly Health Cohort (SREHC), which was conducted from 2019 to 2020. A total of 2,785 participants were included in this study. Kruskal-Wallis rank tests and generalized estimating equation (GEE) models were employed to analyze the association between chronic condition progression and health care utilization. Moderating effect analysis was performed using GEE model and margins plot. Results Older people with progressive chronic conditions used more outpatient (no chronic condition to emerging multimorbidity: OR = 1.83; p = 0.028; one chronic condition to emerging multimorbidity: OR = 2.17; p

Abstract Background Among heart failure patients with obesity, the prognosis is better than those with normal weight, a phenomenon known as the obesity paradox. However, it is unclear whether lipoprotein levels play a mediating role in the machine of the obesity paradox. Methods The study included 1663 heart failure patients hospitalized from January, 2019 through August, 2022. Kaplan-Meier survival analysis and Log-rank tests were performed for three endpoints in order to determine cumulative event-free survival. We investigated the correlation between Body Max Index (BMI) and outcomes by multifactorial Cox models. Mediation analysis was applied to study the presence and magnitude of mediation effects of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B, with the association between BMI and endpoints. Results In MACCEs, the median follow-up period was 679 days. In Cox model, compared with the underweight group, a high BMI level was significantly associated with lower all-cause mortality (HR=0.47, 95%CI 0.31~0.69, p

Abstract Background Wheat is one of major sources of human cadmium (Cd) intake. Reducing the grain Cd concentrations in wheat is urgently required to ensure food security and human health. In this study, we performed a field experiment at Wenjiang experimental field of Sichuan Agricultural University (Chengdu, China) to reveal the effects of FeCl3 and Fe2(SO4)3 on reducing grain Cd concentrations in dwarf Polish wheat (Triticum polonicum L., 2n = 4x = 28, AABB). Results Soil application of FeCl3 and Fe2(SO4)3 (0.04 M Fe3+/m2) significantly reduced grain Cd concentration in DPW at maturity by 19.04% and 33.33%, respectively. They did not reduce Cd uptake or root-to-shoot Cd translocation, but increased Cd distribution in lower leaves, lower internodes, and glumes. Meanwhile, application of FeCl3 and Fe2(SO4)3 up-regulated the expression of TpNRAMP5, TpNRAMP2 and TpYSL15 in roots, and TpYSL15 and TpZIP3 in shoots; they also downregulated the expression of TpZIP1 and TpZIP3 in roots, and TpIRT1 and TpNRAMP5 in shoots. Conclusions The reduction in grain Cd concentration caused by application of FeCl3 and Fe2(SO4)3 was resulted from changes in shoot Cd distribution via regulating the expression of some metal transporter genes. Overall, this study reports the physiological pathways of soil applied Fe fertilizer on grain Cd concentration in wheat, suggests a strategy for reducing grain Cd concentration by altering shoot Cd distribution.

Abstract Background Adverse pregnancy outcomes have reached epidemic proportions in recent years with serious health ramifications, especially for diverse cancers risk. Therefore, we carried out an umbrella review to systematically evaluate the validity and strength of the data and the extent of potential biases of the established association between adverse pregnancy outcomes and cancers risk in both mother and offspring. Methods PubMed, Embase, and Web of Science databases were searched from inception until 18 January 2024. Meta-analyses of observational studies investigating the relationship between adverse pregnancy outcomes and multiple cancers risk in both mother and offspring were included. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. The protocol for this umbrella review was prospectively registered in PROSPERO (CRD42023470544). Results The search identified 129 meta-analyses of observational studies and 42 types of cancer. Moderate certainty of evidence, exhibiting statistical significance, has been observed linking per kilogram increase in birth weight to a heightened risk of breast cancer (OR = 1.07, 95% CI = 1.02–1.12), prostate cancer (OR = 1.02, 95% CI = 1.00–1.05), leukemia (OR = 1.18, 95% CI = 1.13–1.23), and acute lymphoblastic leukemia in offspring (OR = 1.18, 95% CI = 1.12–1.23); rubella infection during pregnancy to an increased risk of leukemia in offspring (OR = 2.79, 95% CI = 1.16–6.71); and a linear dose–response association between an increase in the proportion of optimal birth weight and an elevated risk of acute lymphoblastic leukemia in offspring (OR = 1.16, 95% CI = 1.09–1.24), respectively. Conclusions Although some adverse pregnancy outcomes have clinically promising associations with risk of several cancers in both mother and offspring, it is essential to conduct additional research to solidify the evidence, evaluate causality, and ascertain clinical utility.

Abstract Background Observational studies have demonstrated the alterations of gut microbiota composition in diabetic nephropathy (DN), however, the correlation between gut microbiota and DN remains unclear. Methods A two-sample Mendelian randomization (MR) analysis was designed to estimate the association between gut microbiota and DN. The summary statistics of gut microbiota from phylum level to genus level were obtained from a large-scale, genome-wide association study involving 18,340 individuals, and the data at the species level was derived from the study of TwinsUK Registry, including 1126 twin pairs. The summary statistics of DN were originated from the latest release data of FinnGen (R7, 299623 participants). The MR estimation was calculated using inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was assessed using Cochrane’s Q test. Results Inverse variance weighted results indicated that the order Bacteroidetes and its corresponding class and phylum [odds ratio (OR), 1.58; 95% confidence interval (CI), 1.15–2.17], the family Verrucomicrobiaceae and its corresponding class and order (OR, 1.46; 95% CI, 1.14–1.87), the genera Akkermansia (OR, 1.46; 95% CI, 1.14–1.87) and Catenibacterium (OR, 1.33; 95% CI, 1.07–1.66) might be associated with a higher risk of DN; whereas the genera Coprococcus2 (OR, 0.68; 95% CI, 0.51–0.91) and Eubacterium_coprostanoligenes_group (OR, 0.69; 95% CI, 0.52–0.92) might play protective roles in DN. Conclusions This MR study suggested that several gut bacteria were potentially associated with DN, further studies are required to validate these findings.

Abstract Achieving near-zero-wear remains a major challenge in mechanical engineering and material science. Current ultra-low wear materials are typically developed based on the self-consumption strategy. Here, we demonstrate a new self-repairing approach to achieve near-zero-wear. We find that the WB4-βB/WC tribo-pair has a low wear rate of 10−8 mm3 N−1 m−1 in low vacuum conditions, under a maximum Hertzian contact stress of 2.23 GPa over 1 × 105 friction cycles. Additionally, we observe an abnormal wear phenomenon after 5 × 104 friction cycles, characterized by an increase in the dimensions of the tribo-pair. This near-zero-wear mechanism is attributed to the synergistic action of the super-hard WB4-βB substrate and the self-repairing tribo-oxide layer. This research provides a new approach for advancing wear-resistant materials and enhancing material longevity.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic and lethal lung disorder for which effective treatments remain limited. Recent investigations revealed a potential link between altered glucose metabolism and the activation of fibroblasts, the key cells responsible for generating and depositing extracellular matrix proteins within the lung interstitium during IPF development. Method In this study, we aimed to investigate the potential therapeutic impact of albendazole on fibroblast to myofibroblast transition in IPF. We assess albendazole’s effectiveness in attenuating the activation of fibroblasts. We focused on elucidating the mechanism underlying albendazole's impact on TGF-β1-induced aerobic glycolysis in both lung tissues and fibroblasts obtained from patients with IPF and other lung fibrosis types. Furthermore, the antifibrotic effects of oral administration of albendazole were investigated in mouse models of pulmonary fibrosis induced by BLM or SiO2. Human precision-cut lung slices were employed to evaluate the impact of albendazole following TGF-β1 stimulation. Result In this work, we demonstrated that albendazole, a first-line broad-spectrum anthelmintic drug, effectively attenuated fibroblast to myofibroblast transition through alleviating TGF-β1-induced aerobic glycolysis dependent on the LRRN3/PFKFB3 signaling pathway. Additionally, LRRN3 expression was downregulated in both lung tissues and fibroblasts from patients with IPF and other types of lung fibrosis. Importantly, the levels of LRRN3 correlated with the progression of the disease. Notably, oral administration of albendazole exerted potent antifibrotic effects in mouse models of pulmonary fibrosis induced by BLM or SiO2, and in human precision-cut lung slices after TGF-β1 stimulation, as evidenced by improvements in lung morphology, reduced myofibroblast formation, and downregulation of α-SMA, collagen type 1 and Fibronectin expression in the lungs. Conclusion Our study implies that albendazole can act as a potent agonist of LRRN3 during fibroblast to myofibroblast differentiation and its oral administration shows potential as a viable therapeutic approach for managing IPF.

Objective: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is rare, and manifestations of autonomic dysregulation are diverse and may be overlooked. We aimed to evaluate the incidence of these manifestations. Methods: Patients with ROHHAD syndrome reported before and after 2019 were divided into groups 1 and 2. Patients who were diagnosed at three regional hospitals in China were included in group 3. We collected the age of each specific term of the ROHHAD (neurogenic tumor, NET) acronym and the detailed manifestations of each term, and compared them among the three groups. Results: A total of 16 patients were diagnosed within the 2-year period. Two had neurogenic tumors and cognitive and behavioral abnormalities before developing rapid obesity. At least 93.8% of the patients had ≥ 4 symptoms of autonomic dysregulation. When comparing autonomic dysregulation among groups 1–3, the rates of cardiovascular manifestations were NA vs 12.8% vs 81.2%; gastrointestinal disturbances were 11.4% vs 8.5% vs 62.5%; strabismus was 25.7% vs 12.8% vs 62.5%; sleep disturbance was NA vs 6.4% vs 50.0%; and abnormal pain threshold was NA vs 10.6% vs 25.0% (all P < 0.05). The rates of cognitive and behavioral abnormalities were NA vs 29.8% and 87.5% (P < 0.01). Conclusion: Rapid-onset obesity is not always the first sign of ROHHAD syndrome. Higher rates of autonomic dysregulation and cognitive and behavioral abnormalities with multiple manifestations of autonomic dysregulation coexisted in our cohort, indicating that evaluations of autonomic function and the limbic system should be strengthened when assessing this condition.

Abstract Different human leukocyte antigen (HLA) genotypes have been known to be associated with the risk of development of Sjögren's syndrome in different populations, but this association has never been reported in Taiwan. We enrolled 1044 subjects (673 patients, 371 controls) and tested their HLA‐DR genotypes. We found an increased risk of Sjögren's syndrome in patients carrying HLA‐DR8. DR1 and DR14 were associated with increased risk of eye involvement (uveitis, scleritis or optic neuritis), while DR15 was associated with increased risk of interstitial lung disease. DR8 was associated with increased risk of formation of multiple antibodies: anti‐Ro, rheumatoid factor and antinuclear antibodies (ANA) reaching titer 1:80 or above. DR9 was associated with decreased risk of formation of anti‐La antibodies and increased risk of formation of antithyroglobulin antibodies. DR10 was associated with risk of formation of anticyclic citrullinated peptide (anti‐CCP) antibodies, and DR11 was associated with increased risk of formation of anti‐La antibodies. Oral ulcer was found to be negatively associated with anti‐Ro antibodies and with anti‐ENA antibodies. Skin lesions were associated with ANA antibody titer elevation to 1:80 or above. Malignancies of any kind were associated with the presence of cryoglobulin. Females were more likely to be diagnosed at a younger age than males. There was no statistically significant relationship between HLA‐DR genotype and age at disease diagnosis. In patients with Sjögren's syndrome in Taiwan, the presence of HLA‐DR8 appeared to be a risk factor. In addition, we found several associations between HLA‐DR genotype, clinical presentation, and autoantibody status among them.

Abstract We exploit the holographic duality to study the system of a one-dimensional interface contacting two semi-infinite two-dimensional CFTs. Central to our investigation is the introduction of a dynamical scalar field located on the bulk interface brane which breaks the scaling symmetry of the dual interface field theory, along with its consequential backreaction on the system. We define an interface entropy from holographic entanglement entropy, to construct a g-function. At zero temperature we construct several illustrative examples and consistently observe that the g-theorem is always satisfied. These examples also reveal distinct features of the interface entropy that are intricately linked to the scalar potential profiles. At finite temperature we find that the dynamical scalar field enables the bulk theory to have new configurations which would be infeasible solely with a tension term on the interface brane.

Abstract Background In locally advanced, operable esophageal squamous cell carcinoma (ESCC), neoadjuvant immunochemotherapy (nICT) has shown results that are somewhat comparable to those of standard neoadjuvant chemoradiotherapy (nCRT). The impact of these neoadjuvant treatments on survival outcomes, however, has yet to be elucidated. Methods This study included 489 patients with locally advanced ESCC who underwent surgery at Sichuan Cancer Hospital after receiving neoadjuvant treatment between June 2017 and September 2023. Patients were categorized into nCRT and nICT groups based on whether they received neoadjuvant treatment. To mitigate potential biases and balance covariates between the two cohorts, 1:2 propensity score matching (PSM) was conducted using a caliper width of 0.05. Results After PSM, the baseline characteristics of the 360 patients remained balanced between the two groups. The findings indicated a superior pathological response in the nCRT group, as evidenced by significantly greater rates of complete response (32.87% vs 14.58%, P

Abstract Cutaneous squamous cell carcinoma (CSCC) is common among the elderly, typically treated with surgery. However, for surgery-ineligible patients or those with non-healing wounds progressing to malignant ulcers, non-surgical local treatments are viable. This case details an 80-year-old with recurrent back CSCC and intractable malignant ulcers post-radiotherapy and chemotherapy. Treatment involved Hematoporphyrin Derivative (HpD) Photodynamic Therapy (PDT) with low-dose cindilimab immunotherapy (intravenous and intralesional). Two cycles achieved lesion remission, altering peripheral immune cell counts. HpD-PDT combined with immunotherapy is promising for treating CSCC, particularly with malignant ulcers.

AIM: To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease (CTD-ILD) and healthy controls (HCs) by optical coherence tomography angiography (OCTA) and to investigate the changes in microvascular density in abnormal eyes. METHODS: For a retrospective case-control study, a total of 16 patients (32 eyes) diagnosed with CTD-ILD were selected as the ILD group. The 16 healthy volunteers with 32 eyes, matched in terms of age and sex with the patients, were recruited as control group. The macular retina's superficial retinal layer (SRL) and deep retinal layer (DRL) were examined and scanned using OCTA in each individual eye. The densities of retinal microvascular (MIR), macrovascular (MAR), and total microvascular (TMI) were calculated and compared. Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods: central annuli segmentation method (C1-C6), hemispheric segmentation method [uperior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)], and Early Treatment Diabetic Retinopathy Study (ETDRS) methods [superior (S), inferior (I), left (L), and right (R)]. The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis. RESULTS: The OCTA data demonstrated a statistically significant difference (P

Abiotic and biotic stressors adversely affect plant survival, biomass generation, and crop yields. As the global availability of arable land declines and the impacts of global warming intensify, such stressors may have increasingly pronounced effects on agricultural productivity. Currently, researchers face the overarching challenge of comprehensively enhancing plant resilience to abiotic and biotic stressors. The secondary cell wall plays a crucial role in bolstering the stress resistance of plants. To increase plant resistance to stress through genetic manipulation of the secondary cell wall, we cloned a cell wall protein designated glycine-rich protein-like (GhGRPL) from cotton fibers, and found that it is specifically expressed during the period of secondary cell wall biosynthesis. Notably, this protein differs from its Arabidopsis homolog, AtGRP, since its glycine-rich domain is deficient in glycine residues. GhGRPL is involved in secondary cell wall deposition. Upregulation of GhGRPL enhances lignin accumulation and, consequently, the thickness of the secondary cell walls, thereby increasing the plant's resistance to abiotic stressors, such as drought and salinity, and biotic threats, including Verticillium dahliae infection. Conversely, interference with GhGRPL expression in cotton reduces lignin accumulation and compromises that resistance. Taken together, our findings elucidate the role of GhGRPL in regulating secondary cell wall development through its influence on lignin deposition, which, in turn, reinforces cell wall robustness and impermeability. These findings highlight the promising near-future prospect of adopting GhGRPL as a viable, effective approach for enhancing plant resilience to abiotic and biotic stress factors.