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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 [...]

The upper cervical spine has a complex anatomical structure, making anterior surgical approaches challenging and prone to complications. This study aims to explore the use of bilateral submandibular incisions to provide safer and more convenient exposure of the upper cervical spine and to assess the feasibility of this approach for anterior surgical treatment of complex upper cervical diseases. From November 2019 to August 2021, three patients with malignant tumors of the upper cervical spine were subjected to an anterior–posterior combined approach for cervical tumor resection. The cohort consisted of one male and two females, aged between 41 and 51 years. The anterior approach began with a submandibular incision, followed by blunt dissection through the prevertebral muscles to expose the diseased vertebra. Subsequently, the diseased vertebra was excised, and either a titanium cage or a pre‐customized 3D‐printed artificial vertebral body was implanted anteriorly. Then, posterior fixation of the cervical spine was performed using pedicle screws to provide additional stability. Follow‐up ranged from 8 to 34 months. All patients experienced varying degrees of pain relief within 24 hours post‐operation. Frankel grading showed improvement by at least one grade in all three cases. Regular X‐ray and magnetic resonance imaging examinations revealed no tumor recurrence or involvement of adjacent vertebrae in the surgical area. The anterior bilateral submandibular horizontal incision approach offers comprehensive exposure of the anatomical structures of the upper cervical spine. This approach introduces a new option for the anterior treatment of upper cervical spine diseases.

Tomato (Solanum lycopersicum), an economically important vegetable crop cultivated worldwide, often suffers massive financial losses due to Phytophthora infestans (P. infestans) spread and breakouts. Arbuscular mycorrhiza (AM) fungi mediated biocontrol has demonstrated great potential in plant resistance. However, little information is available on the regulation of mycorrhizal tomato resistance against P. infestans. Therefore, microRNAs (miRNAs) sequencing technology was used to analyse miRNA and their targets in the mycorrhizal tomato after P. infestans infection. Our study showed a lower severity of necrotic lesions in mycorrhizal tomato than in nonmycorrhizal controls. We investigated 35 miRNAs that showed the opposite expression tendency in mycorrhizal and nonmycorrhizal tomato after P. infestans infection when compared with uninfected P. infestans. Among them, miR319c was upregulated in mycorrhizal tomato leaves after pathogen infection. Overexpression of miR319c or silencing of its target gene (TCP1) increased tomato resistance to P. infestans, implying that miR319c acts as a positive regulator in tomato after pathogen infection. Additionally, we examined the induced expression patterns of miR319c and TCP1 in tomato plants exposed to salicylic acid (SA) treatment, and SA content and the expression levels of SA-related genes were also measured in overexpressing transgenic plants. The result revealed that miR319c can not only participates in tomato resistance to P. infestans by regulating SA content, but also indirectly regulates the expression levels of key genes in the SA pathway by regulating TCP1. In this study, we propose a novel mechanism in which the miR319c in mycorrhizal tomato increases resistance to P. infestans.

Abstract The role and detailed mechanisms of lncRNAs in idiopathic pulmonary fibrosis (IPF) are not fully understood. qPCR was conducted to verify lncRNA FEZF1-AS1 expression in the transforming growth factor-beta 1 (TGF-β1)-stimulated human lung fibroblasts (HLF) and A549. The EMT-related proteins were performed by western blotting. Cell proliferation, migration, and transition were detected by CCK-8, colony formation, wound-healing and transwell assays. A dual-luciferase reporter assay was conducted to validate the target relationship of FEZF1-AS1 and miR-200c-3p. FEZF1-AS1 is highly expressed in the fibrotic A549 and HLF. in vitro experiments revealed that FEZF1-AS1 facilitates cell proliferation, migration and invasion. Knockdown of FEZF1-AS1 attenuated TGF-b1-induced fibrogenesis both in vitro. Moreover, silencing FEZF1-AS1 inhibited fibrogenesis through modulation of miR-200c-3p. In addition, inhibition of miR-200c-3p promoted fibrogenesis by regulation of Zinc finger E-box binding homeobox 1 (ZEB1). Mechanistically, FEZF1-AS1 promoted lung fibrosis by acting as a competing endogenous RNA (ceRNA) for miR-200c-3p. FEZF1-AS1 silencing increased the expression and activity of miR-200c-3p to inhibit ZEB1 and alleviate lung fibrogenesis in A549 and HLF. In addition, our study showed that FEZF1-AS1 can regulate enhancer of zeste homolog2 (EZH2) to upregulate fibrosis-related proteins and promote lung fibrosis. In summary, the results of our study revealed the pulmonary fibrogenic effect of FEZF1-AS1 in cellular experiments, demonstrating the potential roles and mechanisms of the FEZF1-AS1/miR-200c-3p/ZEB1 and FEZF1-AS1/EZH2 pathways, which provides a novel and potential therapeutic target to lung fibrosis.

Abstract Knee osteoarthritis is characterized by articular cartilage wear, with its morphological progression not fully understood. This study aimed to elucidate factors contributing to femoral cartilage defects and their expansion in medial knee osteoarthritis, using a novel approach analyzing cross-sectional MRI data arranged by disease severity. From a cohort of 277 women in the Kanagawa Knee Study, we selected 17 knees that showed a cartilage area ratio

Abstract Background Hemifacial spasm (HFS) is a neuromuscular disorder characterized by unilateral facial muscle spasms, negatively impacts quality of life due to social embarrassment. Botulinum Neurotoxin (BoNT) injections have emerged as a viable therapeutic approach. This systematic review evaluated the efficacy and safety of BoNT injections for HFS management, along with effects on patients’ quality of life and mental health. Materials and methods A systematic search for studies on BoNT treatment for HFS published between January 1, 2000, and May 1, 2024, was performed across major databases. Study quality was evaluated using Cochrane and Joanna Briggs Institute (JBI) tools, with data management handled by EndNote X9 and statistical analyses conducted via Review Manager (RevMan 5.4) and STATA 14.0. Results Thirty-five studies met the inclusion criteria: 2 RCTs comprising 83 HFS patients compared the efficacy of perioral injections of botulinum toxin and placebo, while 33 single-arm studies reported outcomes for 2786 patients post-BoNT injection. The selection of 17 single-arm studies focused on the effectiveness rate as the key outcome metric. Pooled estimate signified a remarkably high effectiveness (ES: 0.882, 95% CI: 0.830, 0.926, P

Abstract Clade A type 2C protein phosphatases (PP2Cs) are crucial components of the abscisic acid (ABA) signaling pathway. Research on clade A PP2Cs has focused more on their roles related to ABA signaling and stress responses than on the molecular mechanisms mediating their effects on plant growth and grain yield. Rice (Oryza sativa L.) is an important food crop worldwide. We previously determined that OsPP2C49, which encodes a rice clade A PP2C family member, negatively controls rice responses to drought, salt, and high-temperature stresses. In this study, we investigated the regulatory effects of OsPP2C49 on ABA responses and rice grain yield. By analyzing potential interactions with core ABA components, including pyrabactin resistance 1 (PYR1)/PYR1-like (PYL)/regulatory component of the ABA receptor (RCAR) and stress-activated protein kinases (SAPKs), we confirmed that OsPP2C49 is involved in the ABA signaling pathway. OsPP2C49 overexpression led to decreased ABA sensitivity and increased rice grain yield; the opposite phenotypes were observed in the ospp2c49 knockout mutants. Therefore, OsPP2C49 negatively regulates ABA responses, but positively modulates rice grain yield. Furthermore, we found that OsPP2C49 can interact with and dephosphorylate five OsSAPKs in vitro. Unlike OsPP2C49, these OsSAPKs positively modulate ABA responsiveness, but negatively affect rice yield. These findings indicate that OsPP2C49 may partially regulate ABA responses and rice grain production by dephosphorylating OsSAPKs. This study preliminarily explored the molecular basis of the regulatory effects of OsPP2C49 on rice plant growth and grain yield.

Abstract The identification of predictors for immunotherapy is often hampered by the absence of control groups in many studies, making it difficult to distinguish between prognostic and predictive biomarkers. This study presents biomarker analyses from the phase 3 CONTINUUM trial (NCT03700476), the first to show that adding anti-PD-1 (aPD1) to chemoradiotherapy (CRT) improves event-free survival (EFS) in patients with locoregionally advanced nasopharyngeal carcinoma. A dynamic single-cell atlas was profiled using mass cytometry on peripheral blood mononuclear cell samples from 12 pairs of matched relapsing and non-relapsing patients in the aPD1-CRT arm. Using a supervised representation learning algorithm, we identified a Ki67+ proliferating regulatory T cells (Tregs) population expressing high levels of activated and immunosuppressive molecules including FOXP3, CD38, HLA-DR, CD39, and PD-1, whose abundance correlated with treatment outcome. The frequency of these Ki67+ Tregs was significantly higher at baseline and increased during treatment in patients who relapsed compared to non-relapsers. Further validation through flow cytometry (n = 120) confirmed the predictive value of this Treg subset. Multiplex immunohistochemistry (n = 249) demonstrated that Ki67+ Tregs in tumors could predict immunotherapy benefit, with aPD1 improving EFS only in patients with low baseline levels of Ki67+ Tregs. These findings were further validated in the multicenter phase 3 DIPPER trial (n = 262, NCT03427827) and the phase 3 OAK trial of anti-PD-L1 immunotherapy in NSCLC, underscoring the predictive value of Ki67+ Treg frequency in identifying the beneficiaries of immunotherapy and potentially guiding personalized treatment strategies.

Abstract Biomimetic chemical logic gates that can reversibly transform their shape and physical properties in response to their environment are an important research field. Most artificial chemical logic gates, however, rely on changes in the microscopic properties of molecules and ions in solution. Hence, developing chemical logic gates that influence macroscopic properties, such as crystal structures and magnetic and electrical properties, is essential for mimicking in vivo phenomena more accurately. Here, we develop a reset-set flip-flop circuit based on a single crystal that reversibly transforms in the presence of Ca2+ ions in aqueous solutions and is analogous to the chemical logic gate in muscles. During the crystal transformation, the lattice volume undergoes ~39% shrinkage, and the magnetic and electrical properties change considerably. Compared with existing products, the constructed crystalline system more closely resembles the function of actual muscles, which is promising for advancing the field of biomimetics.

Objective Multi‐segmental total en bloc spondylectomy (TES) gradually became more commonly used by clinicians. However, the choice of surgical strategy is unclear. This study aims to investigate the biomechanical performance of different prosthesis types and fixation ranges in multisegmental TES. Methods In this study, a validated finite element model of T12–L2 post‐spondylectomy operations were carried out. The prostheses of these models used either 3D‐printed artificial vertebrae or titanium mesh cages. The fixed range was two or three segment levels. Range of motion, stress distribution of the endplate and internal fixation system, intervertebral disc pressure, and facet joint surface force of four postoperative models and intact model in flexion and extension, as well as lateral bending and rotation were analyzed and compared. Results The type of prosthesis used in the anterior column reconstruction mainly affected the stress of the adjacent endplate and the prosthesis itself. The posterior fixation range had a greater influence on the overall range of motion (ROM), the ROM of the adjacent segment, the stress of the screw‐rod system, and adjacent facet joint surface force. For the model of the same prosthesis, the increase of fixed length resulted in an obvious reduction of ROM. The maximal decrease was 70.23% during extension, and the minimal decrease was 30.19% during rotation. Conclusion In three‐segment TES, the surgical strategy of using 3D‐printed artificial prosthesis for anterior column support and pedicle screws for posterior fixation at both two upper and lower levels respectively can reduce the stress on internal fixation system, endplates, and adjacent intervertebral discs, resulting in a reduced risk of internal fixation failure, and ASD development.

Abstract Ex vivo lung perfusion (EVLP) enables advanced assessment of human lungs for transplant suitability. We developed a convolutional neural network (CNN)-based approach to analyze the largest cohort of isolated lung radiographs to date. CNNs were trained to process 1300 longitudinal radiographs from n = 650 clinical EVLP cases. Latent features were transformed into principal components (PC) and correlated with known radiographic findings. PCs were combined with physiological data to classify clinical outcomes: (1) recipient time to extubation of

ABSTRACT Aims Diabetes mellitus (DM) is closely associated with Alzheimer's disease (AD), and is considered an accelerator of AD. Our previous study has confirmed that the Calpain inhibitor Calpeptin may alleviate AD‐like complications of diabetes mellitus. This work further investigated its underlying mechanism. Materials and Methods Diabetes mellitus rat model was constructed by a high‐fat and high‐sugar diet combined with streptozotocin, followed by the administration of Calpeptin. Moreover, rats were micro‐injected with LV‐TXNIP‐OE/vector into the CA1 region of the hippocampus one day before streptozotocin injection. The Morris water maze test assessed the spatial learning and memory ability of rats. Immunohistochemistry and western blotting detected the expression of the pericyte marker PDGFRβ, tight junction proteins occludin and ZO‐1, calpain‐1, calpain‐2, APP, Aβ, Aβ‐related, and TXNIP/NLRP3 inflammasome‐related proteins. Immunofluorescence staining examined the blood vessel density and neurons in the hippocampus. Evans blue extravasation and fluorescence detected the permeability of the blood–brain barrier (BBB) in rats. Additionally, the oxidative stress markers and inflammatory‐related factors were assessed by enzyme‐linked immunosorbent assay. Results Calpeptin effectively reduced the expression of Calpain‐2 and TXNIP/NLRP3 inflammasome‐related proteins, improved the decreased pericyte marker (PDGFR‐β) and cognitive impairment in hippocampus of DM rats. The neuronal loss, microvessel density, permeability of BBB, Aβ accumulation, inflammation, and oxidative stress injury in the hippocampus of DM rats were also partly rescued by calpeptin treatment. The influence conferred by calpeptin treatment was reversed by TXNIP overexpression. Conclusions These data demonstrated that calpeptin treatment alleviated AD‐like symptoms in DM rats through regulating TXNIP/NLRP3 inflammasome. Thus, calpeptin may be a potential drug to treat AD‐like complications of diabetes mellitus.

Primary racemose hemangioma of the bronchial artery (RHBA) is a rare congenital condition characterized by enlarged and convoluted bronchial arteries, often forming fistulas between the pulmonary artery or vein. Herein, we report a case of balloon-assisted embolization using N-butyl-2-cyanoacrylate (NBCA) performed for a primary RHBA in an asymptomatic 57-year-old woman. There were 2 tortuous and dilated branches of the right bronchial artery (RBA) (arising from the left subclavian artery and the descending thoracic aorta) which merged in the right pulmonary hilar region, forming multiple aneurysms that short-circuited the right pulmonary artery. Embolization was performed via the RBA arising from the subclavian artery using a triaxial system (a 5-Fr guiding catheter, a 2.7-Fr microballoon catheter, and a 1.9-Fr microcatheter). The guiding catheter was inserted into the peripheral side of the RBA using the microballoon catheter as an anchor; the balloon was slightly inflated and advanced further into the peripheral side using blood flow. The microcatheter was inserted as close to the aneurysms as possible and embolization was done using an NBCA-iodized oil mixture under blood flow control by the microballoon catheter. Bronchial artery embolization is the treatment of choice for primary RHBA because of the risk of rupture, and balloon-assisted techniques can help guide the catheter distally while also controlling blood flow.

Purpose Staff is essential to the university’s efficient administrative operations, which are critical for education, research, and service. Medical schools, often independent, need specialized administrative elements. This study explores how medical school staff perceives the organization using the Six-Box model and evaluates their perceived organizational support, job satisfaction, and organizational commitment based on the concept of job attitudes. Methods This study employs a mixed-methods approach, integrating quantitative and qualitative data via a convergent parallel design. It simultaneously collects and analyzes data from a survey and consensus workshop for medical school staff. The survey data were statistically analyzed (IBM SPSS ver. 25.0; IBM Corp., USA), and the workshop discussions were subjected to content analysis. The findings combined provide a comprehensive understanding of the medical school administrative system. Results Quantitative analysis revealed purpose (3.80) as the highest-rated organizational perception and rewards (2.72) as the lowest. Similarly, job satisfaction was highest (3.63) in job attitudes, while perceived organizational support (2.96) was the lowest. Group differences were observed by gender, enrollment capacity, and contract type (p

Erwinia pyrifoliae is a gram-negative bacterial pathogen that commonly causes black shoot blight in pear and apple tree. Although the pathogenicity of this bacterial species is very similar to E. amylovora, there is no specific explanation of its pathogenic genes and mechanisms. In this study, our investigation into E. pyrifoliae pathogenicity involved generating seven YKB12327 mutant strains using Tn5 transposon mutagenesis. Observations revealed weakened growth rate and loss of pathogenicity in these mutants. Whole-genome sequencing and alignment analysis identified transposon insertions within the coding sequences of five strains and in the intergenic region of two strains. Annotation analysis elucidated genes directly or indirectly associated with pathogenicity. Notably, mutant strain MT16 displayed a transposon insertion mutation in the cyclic-di-GMP phosphodiesterase (pdeF) gene, a key player in bacterial signaling, governing microbial behavior and adaptation to environmental changes. Our findings provide insights into the genetic regulation of E. pyrifoliae pathogenicity, suggesting potential avenues for further research aimed at understanding and controlling this bacterial pathogen by targeting pdeF to mitigate apple black shoot blight disease.

Abstract Recent evidence indicates that liver cirrhosis (LC) is a reversible condition, but there is no established intervention against liver fibrosis. Although the gut microbiota is considered involved in the pathogenesis of LC, the underlying mechanisms remain unclear. Although the antibiotic, rifaximin (RFX), is effective for hepatic encephalopathy (HE) with LC, the impact of RFX on intestinal bacteria is unknown. We investigated the bacterial compositions along the GI tract under RFX treatment using a murine LC model. RFX improved liver fibrosis and hyperammonemia and altered the bacterial composition in the small intestine. The efficacy of RFX was associated with increases in specific bacterial genera, including Akkermansia. Administration of a commensal strain of Akkermansia muciniphila improved liver fibrosis and hyperammonemia with changing bacterial composition in the small intestine. This study proposed a new concept “small intestine-liver axis” in the pathophysiology of LC and oral A. muciniphila administration is a promising microbial intervention.

Abstract Visual-vestibular conflicts can induce motion sickness and further postural instability. Visual-vestibular habituation is recommended to reduce the symptoms of motion sickness and improve postural stability with an altered multisensory reweighting progress. However, it is unclear how the human brain reweights multisensory information after repeated exposure to visual-vestibular conflicts. Therefore, we synchronized a rotating platform and a virtual scene to present visual-vestibular congruent (natural visual stimulation) and incongruent (conflicted visual stimulation) conditions and collected EEG and center of pressure (COP) data. We constructed the effective brain connectivity of region of interest (ROI) derived from source-space EEG in theta-band activity, and quantified the postural stability and the inflow and outflow of each ROI. We found repeated exposure to congruent and incongruent conditions both decreased COP path length and increased COP complexity. Besides, we found that repeated exposure to the incongruent environment decreased the inflow into visual cortex, suggesting the brain down-weighted the less reliable visual information for postural stability. In contrast, repeated exposure to the congruent environment increased the inflow into posterior parietal cortex and the outflow from visual cortex and S1, suggesting an increase in efficiency of multisensory integration. We concluded that repeated exposure to congruent and incongruent conditions both improved postural stability with different multisensory reweighting patterns as revealed by different dynamic changes of brain networks.

Abstract Background Prostate cancer (PCa) represents a significant health challenge for men, and the advancement of the disease often results in a grave prognosis for patients. Therefore, the identification of biomarkers associated with the diagnosis and prognosis of PCa holds paramount importance in patient health management. Methods The datasets pertaining to PCa were retrieved from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted to investigate the modules specifically associated with the diagnosis of PCa. The hub genes were identified using the LASSO regression analysis. The expression levels of these hub genes were further validated by qRT-PCR experiments. Receiver operating characteristic (ROC) curves and nomograms were employed as evaluative measures for assessing the diagnostic value. Results The blue module identified by WGCNA exhibited a strong association with PCa. Six hub genes (SLC14A1, COL4A6, MYOF, FLRT3, KRT15, and LAMB3) were identified by LASSO regression analysis. Further verification confirmed that these six genes were significantly downregulated in tumor tissues and cells. The six hub genes and the nomogram demonstrated substantial diagnostic value, with area under the curve (AUC) values ranging from 0.754 to 0.961. Moreover, patients with low expression levels of these six genes exhibited elevated T/N pathological stage and Gleason score, implying a more advanced disease state. Meanwhile, their progression-free survival (PFS) was observed to be potentially poorer. Finally, a significant association could be observed between the expression of these genes and the dysregulation of immune cells, along with drug sensitivity. Conclusions In summary, our study identified six hub genes, namely SLC14A1, COL4A6, MYOF, FLRT3, KRT15, and LAMB3, which can be utilized to establish a diagnostic model for PCa. The discovery may offer potential molecular targets for clinical diagnosis and treatment of PCa.

Abstract Allosteric drugs offer a new avenue for modern drug design. However, the identification of cryptic allosteric sites presents a formidable challenge. Following the allostery nature of residue-driven conformation transition, we propose a state-of-the-art computational pipeline by developing a residue-intuitive hybrid machine learning (RHML) model coupled with molecular dynamics (MD) simulation, through which we can efficiently identify the allosteric site and allosteric modulator as well as reveal their regulation mechanism. For the clinical target β2-adrenoceptor (β2AR), we discover an additional allosteric site located around residues D792.50, F2826.44, N3187.45 and S3197.46 and one putative allosteric modulator ZINC5042. Using Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and protein structure network (PSN), the allosteric potency and regulation mechanism are probed to further improve identification accuracy. Benefiting from sufficient computational evidence, the experimental assays then validate our predicted allosteric site, negative allosteric potency and regulation pathway, showcasing the effectiveness of the identification pipeline in practice. We expect that it will be applicable to other target proteins.

Abstract Background The purpose of this network meta-analysis was to assess the impact of different protective ventilatory strategies on postoperative pulmonary complications (PPCs). Methods Several databases were searched for randomized controlled trials (RCTs) that were published before October 2023 in a network meta-analysis. We assessed the effect of different lung-protective ventilation strategies on the incidence of PPCs using Bayesian network meta-analysis. Results We included 58 studies (11610 patients) in this meta-analysis. The network meta-analysis showed that low tidal volumes (LTVs) combined with iPEEP and recruitment manoeuvres (RM) was associated with significantly lower incidence of PPCs [HTVs: OR = 0.38, 95%CrI (0.19, 0.75), LTVs: OR = 0.33, 95%CrI (0.12, 0.82)], postoperative atelectasis[HTVs: OR = 0.2, 95%CrI (0.08, 0.48), LTVs: OR = 0.47, 95%CrI (0.11, 0.93)], and pneumonia[HTVs: OR = 0.22, 95%CrI (0.09, 0.48), LTVs: OR = 0.27, 95%CrI (0.08,0.89)] than was High tidal volumes (HTVs) or LTVs. LTVs combined with medium-to-high PEEP and RM were associated with significantly lower incidence of postoperative atelectasis, and pneumonia. Conclusion LTVs combined with iPEEP and RM decreased the incidence of PPCs, postoperative atelectasis, and pneumonia in noncardiac surgery patients. Individual PEEP-guided ventilation was the optimal lung protection ventilation strategy. The quality of evidence is moderate. Trial registration PROSPERO identifier CRD42023399485.

Background: Despite providing valuable staging and prognostic information, the therapeutic benefit of pelvic lymph node dissection (PLND) remains uncertain. We sought to assess the effect of extended PLND (ePLND) on the biochemical recurrence (BCR) of patients with National Comprehensive Cancer Net (NCCN) high- or very high-risk prostate cancer treated via robot-assisted radical prostatectomy (RARP). Methods: We used a multi-institutional database (six centers) to assess 989 patients who underwent RARP from 2014 to 2022 with or without ePLND, among which 699 patients underwent BCR analysis. We performed 1:1 propensity score matching to account for potential differences between the two groups and compared them in terms of BCR-free survival. Cox's regression models were used to test the effect of ePLND on BCR. Results: A total of 585 patients underwent ePLND and 404 did not. A median of 19 lymph nodes was removed in the ePLND cohort. After propensity score matching, no significant differences in BCR-free survival were observed between the two cohorts (HR 1.108, 95% CI 0.776–1.582, p = 0.556). Multivariable Cox's regression models adjusted for the preoperative and postoperative tumor characteristics revealed that PLND was not an independent predictor of BCR. Conclusion: No significant differences in BCR-free survival were observed between NCCN high- or very high-risk prostate cancer patients who underwent PLND during RARP and those who did not. The therapeutic utility of PLND thus remains unclear.

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.