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Abstract Background Diarrhoea has become one of the major areas of concern due to its high mortality rate contributing it to be the second largest cause of death in world. To explore the effectiveness of medicinal plant, the present investigation was undertaken to scientifically justify the traditional claim of the ethanolic root extract of the plant Begonia rubrovenia (EBV) against diarrhoea. Results EBV was standardized using HPLC with quercetin as marker and was further subjected to normal fecal excretion study at 100, 200 and 300 mg/kg, p.o. along with quercetin and loperamide. The study confirmed the effectiveness of EBV at 200 and 300 mg/kg followed by quercetin. In castor oil induced diarrhoea rat model, EBV at 200 and 300 mg/kg significantly delayed onset of diarrhoea, reduced the diarrhoeal faecal output which contributed in higher % protection. The effectiveness of EBV at 200 mg/kg was also confirmed through gastrointestinal motility, fluid accumulation and PGE2 induced enteropooling tests. EBV and its marker quercetin also reduced the elevated level of NO and cytokines and restored the alterations in antioxidant enzymes, ions and enhanced Na+/K+–ATPase activity. Molecular docking, dynamics and network pharmacology study confirmed the role of quercetin in modulating the inflammatory mediators IL-1β, TNF-α and EP3 prostanoid receptor, where quercetin formed more stable complex with EP3 prostanoid receptor. Conclusion The study has scientifically justified the traditional use of the plants B. rubrovenia in treating diarrhoea, where quercetin played a critical role in the observed antidiarrhoeal potential of B. rubrovenia contributing in maintaining electrolyte balance, antioxidant status and inhibiting inflammatory mediators.

The 90th Minute is a documentary film that sheds light on problems that female athletes face in professional sports.The half-hour film reflects on why professional women’s soccer struggles for survival while it is also one of the most popular sports among girls in the United States. The story is told through the lives of three athletes who are in the Women’s Professional Soccer League that started in 2009. They play for the top club team in the world called FC Gold Pride, with Olympic gold medalists, former World Cup competitors and Marta Vieira Da Silva - the best female soccer player in the world.The main characters are Kim Yokers, a former University of California, Berkeley soccer star whose initial dream to play professionally was shattered when the first women’s professional league folded in 2003; Rosie Tantillo, a University of Southern California graduate and PAC-10 award winner who is a developmental player in the new league; and Ali Riley – a young and talented rookie who has a bright career in front of her. Despite their success, the three athletes face major obstacles in their careers that force them to think critically about how much they are willing to give up to play professional soccer.The film looks back at the 1999 Women’s World Cup - when Mia Hamm empowered thousands of young girls to play soccer, Brandi Chastain fell to her knees in her sports bra after kicking the final game’s winning goal, and the U.S. National Team surprised the country with their athleticism, charisma and ability to win. The tournament was an iconic example of how far women had come in sports.The 90th Minute gives a voice to female athletes who have yet to reach their potential because of continuing gender inequities in sports.

Maize is one of the essential food crops in Uganda. This paper aims to examine the consumer preference for branded maize flour in urban Uganda and inform branded maize flour suppliers of the findings. The study empirically examines how the purchase of branded maize flour is influenced by consumer characteristics using survey data and a binary logit model. The survey was conducted in Kampala in October 2014. The dependent variable is the purchase of branded maize flour. Independent variables are monthly individual income, family size, gender, age, education, and quantity of purchase. The study reveals that almost half of respondents purchased branded maize flour. The results suggest that education and purchased quantity are positively and significantly related to the probability of purchasing branded maize flour. Also, the study found that gender affected the probability of purchasing branded maize flour. The probability of respondents with a college education or higher purchasing branded maize flour is 16% higher than respondents with less than a college education, holding other independent variables constant. The probability of purchasing branded maize flour is 28% greater for consumers who purchase 6 kg to 21 kg of flour compared to consumers who purchase less than 6 kg. The probability of purchasing branded maize flour is 12% greater for female consumers than for male consumers, keeping other variables constant. A clear influence of individual monthly income on the probability of purchasing branded maize flour could not be deduced in this study. Based on these results, it is recommended that suppliers of branded maize flour products in Kampala City, Uganda target female consumers, highly educated, and purchase 6-21kg of maize flour at one time. It would be recommended that further research investigates how price and aggregate household income influence purchase for branded maize flour. The study provides insight into the effect of consumer socioeconomic characteristics on branded maize preferences in the East African region.Key words: Logit Model, Maize, Branded Maize Flour, Uganda, Maganjo, Consumer Preference, INTRODUCTIONMaize is an important income-generating cash crop produced by 57% of Ugandan farmers [1, 2]. In a typical Ugandan diet in 2011, maize provided the majority of daily calories with [...]

In this study, we introduced an innovative and robust semi-supervised learning strategy tailored for high-dimensional data categorization. This strategy encompasses several pivotal symmetry elements. To begin, we implemented a risk regularization factor to gauge the uncertainty and possible hazards linked to unlabeled samples within semi-supervised learning. Additionally, we defined a unique non-second-order statistical indicator, termed $ C_{p} $-Loss, within the kernel domain. This $ C_{p} $-Loss feature is characterized by symmetry and bounded non-negativity, efficiently minimizing the influence of noise points and anomalies on the model's efficacy. Furthermore, we developed a robust safe semi-supervised extreme learning machine (RS3ELM), grounded on this educational framework. We derived the generalization boundary of RS3ELM utilizing Rademacher complexity. The optimization of the output weight matrix in RS3ELM is executed via a fixed point iteration technique, with our theoretical exposition encompassing RS3ELM's convergence and computational complexity. Through empirical analysis on various benchmark datasets, we demonstrated RS3ELM's proficiency and compared it against multiple leading-edge semi-supervised learning models.

Abstract Background Whole exome sequencing (WES) has been recommended to investigate the genetic cause of fetal structural anomalies. In this retrospective study, we aimed to evaluate the diagnostic yield of WES in our cohort of families with pregnancy loss or termination of pregnancy due to structural anomalies. Methods As aneuploidy, triploidy and copy number variations (CNVs) could be detected by exome-based CNV analysis, only WES is performed in this study. And the results of 375 cases assessed by WES were analyzed. Results The overall detection rate was 32.3% (121/375), including aneuploidy and triploidy (7.5%, 28/375), CNVs (5.1%, 19/375) and single-nucleotide variants (SNVs) /insertions or deletions (Indels) (19.7%, 74/375). Among these, the diagnostic yield for likely pathogenic (LP) or pathogenic (P) CNVs is 4.8% (18/375), and the diagnostic yield for LP or P SNVs/Indels is 15.2% (57/375). And an additional 4.8% (18/375) of cases had CNVs or SNVs/Indels classified as variants of uncertain significance (VUS) with potential clinical significance. Conclusions Our findings expand the known mutation spectrum of genetic variants related to fetal abnormalities, increase our understanding of prenatal phenotypes, and enable more accurate counseling of recurrence risk for future pregnancies.

Abstract Background Current research lacks comprehensive investigation into the biomechanical changes in the spinal cord and nerve roots during scoliosis correction. This study employs finite element analysis to extensively explore these biomechanical variations across different Cobb angles, providing valuable insights for clinical treatment. Methods A personalized finite element model, incorporating vertebrae, ligaments, spinal cord, and nerve roots, was constructed using engineering software. Forces and displacements were applied to achieve Cobb angle improvements, designating T1/2-T4/5 as the upper segment, T5/6-T8/9 as the middle segment, and T9/10-L1/2 as the lower segment. Simulations under traction, pushing, and traction + torsion conditions were conducted, and biomechanical changes in each spinal cord segment and nerve roots were analyzed. Results Throughout the scoliosis correction process, the middle spinal cord segment consistently exhibited a risk of injury under various conditions and displacements. The lower spinal cord segment showed no significant injury changes under traction + torsion conditions. In the early correction phase, the upper spinal cord segment demonstrated a risk of injury under all conditions, and the lower spinal cord segment presented a risk of injury under pushing conditions. Traction conditions posed a risk of nerve injury on both sides in the middle and lower segments. Under pushing conditions, there was a risk of nerve injury on both sides in all segments. Traction + torsion conditions implicated a risk of injury to the right nerves in the upper segment, both sides in the middle segment, and the left side in the lower segment. In the later correction stage, there was a risk of injury to the upper spinal cord segment under traction + torsion conditions, the left nerves in the middle segment under traction conditions, and the right nerves in the upper segment under pushing conditions. Conclusion When the correction rate reaches 61–68%, particular attention should be given to the upper-mid spinal cord. Pushing conditions also warrant attention to the lower spinal cord and the nerve roots on both sides of the main thoracic curve. Traction conditions require attention to nerve roots bilaterally in the middle and lower segments, while traction combined with torsion conditions necessitate focus on the right-side nerve roots in the upper segment, both sides in the middle segment, and the left-side nerve roots in the lower segment.

Abstract Background Carbon dots (CDs) derived from Citrus aurantifolia represent a promising platform for advanced cancer therapy and diagnostics (theranostics). These CDs are synthesized through a sustainable and cost-effective hydrothermal method, utilizing fruit juice as a green carbon source. Despite the potential, research on the synthesis of citrus-based CDs, especially regarding their red fluorescence emission, which is crucial for enhanced tissue penetration and biomedical efficacy, remains limited. Results In this study, CDs were successfully synthesized from C. aurantifolia fruit, yielding nanoparticles below 5 nm in size (PDI 0.231 ± 0.04). Characterization revealed favorable optical properties, including excitation-dependent fluorescent behavior with prominent red emission under higher excitation wavelengths, a quantum yield of 8.17%, and stable photoluminescence. Chemical composition analysis using XPS, FTIR, and XRD confirmed the purity and structure of the CDs. To explore their biomedical application, CDs were co-loaded with curcumin into liposomes. The formulations had a mean size of 177.2 ± 3.6 nm (PDI 0.270 ± 0.012), demonstrated efficient drug entrapment (60.32 ± 2.24%), and exhibited rapid release kinetics, with 90.21 ± 2.16% of the drug release within 8 h. In vitro studies using A549 lung cancer cells demonstrated superior cellular uptake and cytotoxicity of Cur-CD-loaded liposomes compared to curcumin alone (Cur-Suspension), achieving IC50 values of 0.093 ± 0.011 µg/ml and 0.016 ± 0.006 µg/ml, respectively. Conclusion This research underscores C. aurantifolia as a viable natural source for green CD synthesis. The obtained CDs with red fluorescence emission, optimized through reaction conditions and excitation wavelengths, hold promise for enhanced biological applications, particularly in the realm of lung cancer therapy. The findings advocate for further exploration and refinement of citrus-based CDs as versatile theranostic agents, capitalizing on their sustainable origins and potent biomedical properties. The combination of citrus-derived CDs with curcumin loaded into liposomal formulations represents a potent theranostic strategy for lung cancer treatment, leveraging the unique properties of CDs and their potential for targeted and effective therapy. Graphical abstract

Abstract Nowadays, human activities intensified the combined pollution of fluoride and lead in acidic tea garden soil. The key to eliminating this combined pollution is to immobilize pollutants simultaneously, thus preventing their migration from tea garden soil to tea trees. In this paper, the natural product bayberry tannin was employed as raw material to fabricate functional materials (TF-Zr) for simultaneous adsorption of fluorine (F) and lead (Pb) in water and soil by the reactivity of tannin with Pb2+ and the affinity of Zr with F. SEM-Mapping, EDS, FT-IR, XPS were utilized to probe the immobilization mechanisms. The results showed that TF-Zr could simultaneously and efficiently adsorb F– and Pb2+ from water with the adsorption capacity of 5.02 mg/g (Pb) and 4.55 mg/g (F). The adsorption processes were both in accordance with the proposed secondary kinetic adsorption model. Besides, the presence of F– promoted the adsorption of Pb2+ by TF-Zr. The materials were applied into tea garden soil to explore its effect on the variation of F and Pb forms in the soil. It was found that the proportion of water-soluble fluorine, exchangeable fluorine and exchangeable lead in the tea garden soil decreased significantly, while the proportion of residual fluorine and lead increased evidently, illustrating TF-Zr possessed eximious fixation effect on the highly reactive fluorine and lead in the soil and facilitated their conversion to the more stable residue state. Therefore, TF-Zr can be used for the efficient and simultaneous immobilization of fluorine and lead in water and tea garden soil.

Introduction Transplant renal vein thrombosis is a serious post‐transplant complication. We report a case in which a thrombus was found in the transplant renal vein and rescued the transplanted kidney utilizing interventional radiology. Case presentation A 56‐year‐old woman underwent ABO‐compatible living donor renal transplantation due to impaired renal function caused by IgA nephropathy. On postoperative Day 13, there was a finding on transplant renal echocardiography that appeared to be an interruption of peripheral renal blood flow in diastole. Contrast‐enhanced computed tomography revealed that the vein was occluded due to the hematoma, and thrombosis was observed within, and distal contrast showed regurgitation into the collateral vessels. The stenosis was breached and balloon dilation restored progressive blood flow through interventional radiology. Conclusion Although open surgical thrombectomy is mainly considered for treatment for transplant renal vein thrombosis, interventional radiology might be the alternative treatment option.

Abstract Background Generation and regulation (control) of linear and angular momentum is a challenge during turning while walking which may be exacerbated by age-related changes. In healthy older adults, little is known about how momentum is controlled during turns, especially within each phase of gait. Each phase of gait affords unique mechanical contexts to control momenta and regulate balance. In healthy young adults, we found that the transverse-plane linear and angular momenta generation strategies observed within specific phases of gait during straight-line gait were also used during turns. Therefore, in this study, we investigated whether healthy older adults shared similar momentum control strategies specific to each gait phase during straight-line gait and turns. Methods Nine healthy older adults completed straight-line gait and 90° leftward walking turns. We compared the change in transverse-plane whole-body linear and angular momentum across gait phases (left and right single and double support). We also compared the average leftward force and transverse-plane moment across gait phases. Results We found that leftward linear momentum was generated most during right single support in straight-line gait and leftward turns. However, in contrast to straight-line gait, during leftward turns, average leftward force was applied across gait phases, with left single support generating significantly less leftward average force than other gait phases. Leftward angular momentum generation and average moment were greatest during left double support in both tasks. We observed some within-participant results that diverged from the group statistical findings, illustrating that although they are common, these momenta control strategies are not necessary. Conclusions Older adults generated transverse-plane linear and angular momentum during consistent phases of gait during straight-line gait and 90° turns, potentially indicating a shared control strategy. Understanding momentum control within each phase of gait can help design more specific targets in gait and balance training interventions.

Abstract Primary familial brain calcification (PFBC) is a genetic neurological disorder characterized by symmetric brain calcifications that manifest with variable neurological symptoms. This study aimed to explore the genetic basis of PFBC and elucidate the underlying pathophysiological mechanisms. Six patients from four pedigrees with brain calcification were enrolled. Whole-exome sequencing identified two novel homozygous variants, c.488G > T (p.W163L) and c.2135G > A (p.W712*), within the myogenesis regulating glycosidase (MYORG) gene. Cerebellar ataxia (n = 5) and pyramidal signs (n = 4) were predominant symptoms, with significant clinical heterogeneity noted even within the same family. An autopsy of one patient revealed extensive brainstem calcifications, sparing the cerebral cortex, and marked by calcifications predominantly in capillaries and arterioles. The pathological study suggested morphological alterations characterized by shortened foot processes within astrocytes in regions with pronounced calcification and decreased immunoreactivity of AQP4. The morphology of astrocytes in regions without calcification remains preserved. Neuronal loss and gliosis were observed in the basal ganglia, thalamus, brainstem, cerebellum, and dentate nucleus. Notably, olivary hypertrophy, a previously undescribed feature in MYORG-PFBC, was discovered. Neuroimaging showed reduced blood flow in the cerebellum, highlighting the extent of cerebellar involvement. Among perivascular cells constituting the blood-brain barrier (BBB) and neurovascular unit, MYORG is most highly expressed in astrocytes. Astrocytes are integral components of the BBB, and their dysfunction can precipitate BBB disruption, potentially leading to brain calcification and subsequent neuronal loss. This study presents two novel homozygous variants in the MYORG gene and highlights the pivotal role of astrocytes in the development of brain calcifications, providing insights into the pathophysiological mechanisms underlying PFBC associated with MYORG variants.

Abstract Objective To reveal the clinical features and assess risk factors linked to brain fog and its societal implications, including labor productivity, providing valuable insights for the future care of individuals who have experienced coronavirus disease 2019 (COVID‐19). Methods We analyzed a comprehensive cohort dataset comprising 1,009 patients with COVID‐19 admitted to Japanese hospitals. To assess brain fog, we analyzed patients who responded to a questionnaire indicating symptoms such as memory impairment and poor concentration. Results The prevalence of brain fog symptoms decreased 3 months posthospitalization but remained stable up to 12 months. Neurological symptoms such as taste and smell disorders and numbness at hospitalization correlated with a higher frequency of identifying brain fog as a long COVID manifestation. Our findings indicated that advanced age, female sex, a high body mass index, oxygen required during hospitalization, chronic obstructive pulmonary disease, asthma, and elevated C‐reactive protein and elevated D‐dimer levels were risk factors in patients exhibiting brain fog. Additionally, we demonstrated the negative impact of brain fog on labor productivity by presenteeism scores. Interpretations This study clarified the clinical characteristics of patients experiencing brain fog as a long COVID manifestation, specifically emphasizing neurological symptoms during hospitalization and their correlation with brain fog. Additionally, the study identified associated risk factors for its onset and revealed that the emergence of brain fog was linked to a decline in labor productivity.

Abstract Background Post-stroke depression (PSD) is closely associated with poor stroke prognosis. However, there are some challenges in identifying and assessing PSD. This study aimed to identify scales for PSD diagnosis, assessment, and follow-up that are straightforward, accurate, efficient, and reproducible. Methods A systematic literature search was conducted in 7 electronic databases from January 1985 to December 2023. Results Thirty-two studies were included, the Patient Health Questionnaire-9 (PHQ-9) and Hamilton Depression Scale (HDRS) had higher diagnostic accuracy for PSD. The sensitivity, specificity, and diagnostic odds ratio of PHQ-9 or diagnosing any depression were 0.82, 0.87, and 29 respectively. And for HDRS, used for diagnosing major depression, the scores were 0.92, 0.89, and 94. Furthermore, these two scales also had higher diagnostic accuracy in assessing depressive symptoms during both the acute and chronic phases of stroke. In patients with post-stroke aphasia and cognitive impairment, highly diagnostic scales have not been identified for assessing depressive symptoms yet. Conclusions The PHQ-9 and HDRS scales are recommended to assess PSD. HDRS, which demonstrates high diagnostic performance, can replace structured interviews based on diagnostic criteria.

Abstract Background Prostate cancer (PCa) stands as the second most prevalent malignancy impacting male health, and the disease’s evolutionary course presents formidable challenges in the context of patient treatment and prognostic management. Charged multivesicular body protein 4 C (CHMP4C) participates in the development of several cancers by regulating cell cycle functions. However, the role of CHMP4C in prostate cancer remains unclear. Methods In terms of bioinformatics, multiple PCa datasets were employed to scrutinize the expression of CHMP4C. Survival analysis coupled with a nomogram approach was employed to probe into the prognostic significance of CHMP4C. Gene set enrichment analysis (GSEA) was conducted to interrogate the functional implications of CHMP4C. In terms of cellular experimentation, the verification of RNA and protein expression levels was executed through the utilization of qRT-PCR and Western blotting. Upon the establishment of a cell line featuring stable CHMP4C knockdown, a battery of assays, including Cell Counting Kit-8 (CCK-8), wound healing, Transwell, and flow cytometry, were employed to discern the impact of CHMP4C on the proliferation, migration, invasion, and cell cycle function of PCa cells. Results The expression of CHMP4C exhibited upregulation in both PCa cells and tissues, and patients demonstrating elevated CHMP4C expression levels experienced a notably inferior prognosis. The nomogram, constructed using CHMP4C along with clinicopathological features, demonstrated a commendable capacity for prognostic prediction. CHMP4C knockdown significantly inhibited the proliferation, migration, and invasion of PCa cells (LNcaP and PC3). CHMP4C could impact the advancement of the PCa cell cycle, and its expression might be regulated by berberine. Divergent CHMP4C expression among PCa patients could induce alterations in immune cell infiltration and gene mutation frequency. Conclusions Our findings suggest that CHMP4C might be a prognostic biomarker in PCa, potentially offering novel perspectives for the advancement of precision therapy for PCa.

Highlights Blue micro-light-emitting diodes (μLED)-integrated gas sensors were fabricated as monolithic structure by directly loading sensing materials onto the μLED. SnO2 nanoparticles are activated by blue μLED and exhibit outstanding sensitivity to NO2 at μ-Watt power levels. Noble metal (Au, Pd, Pt)-decorated SnO2 showed the tunable gas selectivity for 4 target gases under blue light illumination.

Abstract Collagen, type XV, alpha 1 (COL15A1) belongs to the collagen superfamily, which can influence disease progression by modulating immune pathways. Although the growing number of investigations demonstrating the indispensable role of COL15A1 in the progression of certain tumors, no pan-cancer assessment of COL15A1 is accessible to date. Therefore, the available data was used to explore the role of COL15A1 in 33 types of tumors and to investigate their potential immune function. Numerous bioinformatics approaches were used to research the potential oncogenic role of COL15A1, including analysis of tumor prognosis, microsatellite instability (MSI), tumor mutational burden (TMB), single nucleotide polymorphism (SNP), drug sensitivity, immune cell infiltration, and the correlation between cancer stem cells (CSCs) and COL15A1 expression. The outcome implies that most tumors had a high expression of COL15A1, and COL15A1 manifested different relationships with prognosis in different tumors, including both positive and negative correlations. COL15A1 was also found to have a significant correlation with MSI, TMB, and immune infiltrating cells. Our study suggests that COL15A1 may serve as a prognostic marker for malignancy because of its differential expression in tissues and their function in tumor immunity.

Abstract Most triblock copolymer-based physical hydrogels form three-dimensional networks through micellar packing, and formation of polymer loops represents a topological defect that diminishes hydrogel elasticity. This effect can be mitigated by maximizing the fraction of elastically effective bridges in the hydrogel network. Herein, we report hydrogels constructed by complexing oppositely charged multiblock copolymers designed with a sequence pattern that maximizes the entropic and enthalpic penalty of micellization. These copolymers self-assemble into branched and bridge-rich network units (netmers), instead of forming sparsely interlinked micelles. We find that the storage modulus of the netmer-based hydrogel is 11.5 times higher than that of the micelle-based hydrogel. Complementary coarse grained molecular dynamics simulations reveal that in the netmer-based hydrogels, the numbers of charge-complexed nodes and mechanically reinforcing bridges increase substantially relative to micelle-based hydrogels.

Abstract Current concepts of corticothalamic organization in the mammalian brain are mainly based on sensory systems, with less focus on circuits for higher-order cognitive functions. In sensory systems, first-order thalamic relays are driven by subcortical inputs and modulated by cortical feedback, while higher-order relays receive strong excitatory cortical inputs. The applicability of these principles beyond sensory systems is uncertain. We investigated mouse prefronto-thalamic projections to the midline thalamus, revealing distinct top-down control. Unlike sensory systems, this pathway relies on indirect modulation via the thalamic reticular nucleus (TRN). Specifically, the prelimbic area, which influences emotional and motivated behaviors, impacts instrumental avoidance responses through direct and indirect projections to the paraventricular thalamus. Both pathways promote defensive states, but the indirect pathway via the TRN is essential for organizing avoidance decisions through disinhibition. Our findings highlight intra-thalamic circuit dynamics that integrate cortical cognitive signals and their role in shaping complex behaviors.

Abstract Background Synovial fibrosis is a common complication of knee osteoarthritis (KOA), a pathological process characterized by myofibroblast activation and excessive extracellular matrix (ECM) deposition. Fibroblast-like synoviocytes (FLSs) are implicated in KOA pathogenesis, contributing to synovial fibrosis through diverse mechanisms. Nuclear protein 1 (NUPR1) is a recently identified transcription factor with crucial roles in various fibrotic diseases. However, its molecular determinants in KOA synovial fibrosis remain unknown. This study aims to investigate the role of NUPR1 in KOA synovial fibrosis through in vivo and in vitro experiments. Methods We examined NUPR1 expression in the murine synovium and determined the impact of NUPR1 on synovial fibrosis by knockdown models in the destabilization of the medial meniscus (DMM)-induced KOA mouse model. TGF-β was employed to induce fibrotic response and myofibroblast activation in mouse FLSs, and the role and molecular mechanisms in synovial fibrosis were evaluated under conditions of NUPR1 downexpression. Additionally, the pharmacological effect of NUPR1 inhibitor in synovial fibrosis was assessed using a surgically induced mouse KOA model. Results We found that NUPR1 expression increased in the murine synovium after DMM surgical operation. The adeno-associated virus (AAV)-NUPR1 shRNA promoted NUPR1 deficiency, attenuating synovial fibrosis, inhibiting synovial hyperplasia, and significantly reducing the expression of pro-fibrotic molecules. Moreover, the lentivirus-mediated NUPR1 deficiency alleviated synoviocyte proliferation and inhibited fibroblast to myofibroblast transition. It also decreased the expression of fibrosis markers α-SMA, COL1A1, CTGF, Vimentin and promoted the activation of the SMAD family member 3 (SMAD3) pathway. Importantly, trifluoperazine (TFP), a NUPR1 inhibitor, attenuated synovial fibrosis in DMM mice. Conclusions These findings indicate that NUPR1 is an antifibrotic modulator in KOA, and its effect on anti-synovial fibrosis is partially mediated by SMAD3 signaling. This study reveals a promising target for developing novel antifibrotic treatment.

Spinal cord injury (SCI) is a traumatic condition that results in impaired motor and sensory function. Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord, and ferroptosis inhibitors are effective in reducing inflammation and repairing SCI. Although human umbilical cord mesenchymal stem cells (Huc-MSCs) can ameliorate inflammatory microenvironments and promote neural regeneration in SCI, their efficacy is greatly limited by the local microenvironment after SCI. Therefore, in this study, we constructed a drug-release nanoparticle system with synergistic Huc-MSCs and ferroptosis inhibitor, in which we anchored Huc-MSCs by a Tz-A6 peptide based on the CD44-targeting sequence, and combined with the reactive oxygen species (ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at the other end for SCI repair. Meanwhile, we also modified the classic ferroptosis inhibitor Ferrostatin-1 (Fer-1) and synthesized a new prodrug Feborastatin-1 (Feb-1). The results showed that this treatment regimen significantly inhibited the ferroptosis and inflammatory response after SCI, and promoted the recovery of neurological function in rats with SCI. This study developed a combination therapy for the treatment of SCI and also provides a new strategy for the construction of a drug-coordinated cell therapy system.

Abstract The recent Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic highlights the significant threat coronaviruses (CoVs) pose to public health. With their extensive cross-continental movements, migratory birds have the potential to serve as reservoirs and vectors for CoVs. This study aimed to investigate the prevalence of CoVs in birds in densely populated areas of Guangdong Province, China. Of the 128 samples collected from birds, six tested positive for CoVs (4.7%, 95% CI: 1.7–9.9%), and three complete viral genomes were obtained through viral metagenomics and PCR. Phylogenetic analysis revealed that two CoVs (MD_XN18 and SG_DWY40) belonged to the Gammacoronavirus genus, while one (CP_XN11) belonged to the Deltacoronavirus genus. Homology analysis revealed that the MD_XN18 strain discovered in mallards shares 95.6–97.4% sequence similarity with chicken infectious bronchitis viruses (IBVs), providing direct evidence that migratory mallards can transmit avian IBVs. Recombination analysis suggested that two genomic regions of SG_DWY40 could originate from unknown sources through recombination, potentially leading to the expression of a novel viral protein, provisionally named NS3.5. These findings underscore the ongoing transmission and evolution of CoVs among birds in cities near Guangdong Province, emphasizing the need for continued monitoring and research.

Abstract Background The purpose of this study was to improve the deep learning (DL) model performance in predicting and classifying IMRT gamma passing rate (GPR) by using input features related to machine parameters and a class balancing technique. Methods A total of 2348 fields from 204 IMRT plans for patients with nasopharyngeal carcinoma were retrospectively collected to form a dataset. Input feature maps, including fluence, leaf gap, leaf speed of both banks, and corresponding errors, were constructed from the dynamic log files. The SHAP framework was employed to compute the impact of each feature on the model output for recursive feature elimination. A series of UNet++ based models were trained on the obtained eight feature sets with three fine-tuning methods including the standard mean squared error (MSE) loss, a re-sampling technique, and a proposed weighted MSE loss (WMSE). Differences in mean absolute error, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were compared between the different models. Results The models trained with feature sets including leaf speed and leaf gap features predicted GPR for failed fields more accurately than the other models (F(7, 147) = 5.378, p

Abstract Background No studies have compared mortality between acetate-containing bicarbonate dialysate (ABD) and acetate-free bicarbonate dialysate containing citrate (AFD) in hemodialysis (HD) or online hemodiafiltration (OHDF). We therefore compared mortality between ABD and AFD in each modality. Methods This retrospective observational study included 738 patients who were receiving super high-flux (SHF) or SHF albumin-leaking HD (n = 310: ABD 235 and AFD 75) or OHDF (n = 428: ABD 321 and AFD 107) at our institution between 1 April and 1 July 2017. Three-year all-cause mortality was compared between ABD and AFD in the HD or OHDF groups using a propensity score matching model. Kaplan–Meier survival curves were compared using the log-rank test, and then Cox regression analysis with adjustments was performed for some covariates that remained significant. Results After propensity score matching, mortality on ABD was not significantly different from that on AFD in the HD group [n = 75; hazard ratio (HR) 2.271, 95% confidence interval (CI) 0.863–5.981, P = 0.087] or in the OHDF group (n = 107; HR 1.944, 95% CI 0.585–6.458, P = 0.269) without adjustments. However, with adjustments using some covariates, mortality was significantly higher on ABD than on AFD (adjusted HR 4.501, 95% CI 1.434–14.125, P = 0.010) in the HD group, but not in the OHDF group. Conclusions These findings suggest that ABD worsens mortality more than AFD in patients on SHF and SHF albumin-leaking HD. Trial registration: UMIN Clinical Trials Registry, UMIN000053090. Prospectively registered 13 December 2023, https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000060581 .

Abstract Employing machine learning methods for mapping surface ocean pCO2 has reduced the uncertainty in estimating sea-air CO2 flux. However, a general discrepancy exists between the Southern Ocean carbon sinks derived from pCO2 products and those from biogeochemistry models. Here, by performing a boosting ensemble learning feed-forward neural networks method, we have identified an underestimation of the surface Southern Ocean pCO2 due to notably uneven density of pCO2 measurements between summer and winter, which resulted in about 16% overestimating of Southern Ocean carbon sink over the past three decades. In particular, the Southern Ocean carbon sink since 2010 was notably overestimated by approximately 29%. This overestimation can be mitigated by a winter correction in algorithms, with the average Southern Ocean carbon sink during 1992-2021 corrected to −0.87 PgC yr−1 from the original −1.01 PgC yr−1. Furthermore, the most notable underestimation of surface ocean pCO2 mainly occurred in regions south of 60°S and was hiding under ice cover. As the surface ocean pCO2 under sea ice coverage in the winter is much higher than the atmosphere, if sea ice melts completely, there could be a further reduction of about 0.14 PgC yr−1 in the Southern Ocean carbon sink.