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The IL6-GP130-STAT3 pathway facilitates lung cancer progression and resistance to tyrosine kinase inhibitors. Although glycosylation alters the stability of GP130, its effect on the ligand IL6 remains unclear. We herein find that N-glycosylated IL6, especially at Asn73, primarily stimulates JAK-STAT3 signaling and prolongs STAT3 phosphorylation, whereas N-glycosylation-defective IL6 (deNG-IL6) induces shortened STAT3 activation and alters the downstream signaling preference for the SRC-YAP-SOX2 axis. This signaling shift induces epithelial-mesenchymal transition (EMT) and migration in vitro and metastasis in vivo, which are suppressed by targeted inhibitors and shRNAs against SRC, YAP, and SOX2. Osimertinib-resistant lung cancer cells secrete a large amount of deNG-IL6 through reduced N-glycosyltransferase gene expression, leading to clear SRC-YAP activation. deNG-IL6 contributes to drug resistance, as confirmed by in silico analysis of cellular and clinical transcriptomes and signal expression in patient specimens. Therefore, the N-glycosylation status of IL6 not only affects cell behaviors but also shows promise in monitoring the dynamics of lung cancer evolution. Post-translational modifications regulate tumorigenesis and cancer therapy sensitivity. Here, the authors show that N-glycosylation defective Interleukin-6 (deNG-IL6) switches downstream signalling pathway from JAK-STAT3 to SRC-YAP axis and lung cancer cells secrete deNG-IL6 to promote metastasis and tyrosine kinase inhibitor resistance. [ABSTRACT FROM AUTHOR]

This study aims to discuss the identification of the C1 nerve root as an effective surgical approach to successfully locate the shunting point of craniocervical junction spinal dural arteriovenous fistula (CCJ-SDAVF) intraoperatively. This study included all patients with CCJ-SDAVF who underwent surgical treatment using the far-lateral transcondylar approach at a single institution from January 2017 to June 2023. Data on patient demographics, clinical and angiographic characteristics of CCJ-SDAVF, surgical details, and treatment outcomes were collected. Follow-up assessments were conducted for all patients until December 31, 2023. The study included a total of 7 patients, comprising 5 men(71.4%) and 2 women (28.6%), with an average age of 57.6 years. Among them, 4 patients (57.1%) developed diffuse subarachnoid hemorrhage(SAH), while 2 patients (28.6%) experienced progressive cervical myelopathy. The shunting points of all CCJ-SDAVFs, which exhibited engorged veins, were identified next to the C1 root. Complete obliteration of CCJ-SDAVFs was successfully achieved in all patients, as confirmed by postoperative angiography one month later. No recurrent CCJ-SDAVFs were observed two years after the operation. Among the patients, 5 (71.4%) experienced good functional recovery, as indicated by an mRS score ranging from 0 to 1, while the remaining 2 patients (28.6%) showed incomplete functional recovery. The surgical interruption of CCJ-SDAVFs is the preferred treatment option, given its high obliteration rate and favorable functional recovery outcomes. We advocate the identification of C1 spinal nerve root as a crucial surgical step to identify the shunting points of CCJ- SDAVFs. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined the preoperative risks and healthcare costs related to free flap revision in hypopharyngeal cancer (HPC) patients. Methods: A 20-year retrospective case–control study was conducted using the Chang Gung Research Database, focusing on HPC patients who underwent tumor excision and free flap reconstruction from January 1, 2001, to December 31, 2019. The impacts of clinical variables on the need for re-exploration due to free flap complications were assessed using logistic regression. The direct and indirect effects of these complications on medical costs were evaluated by causal mediation analysis. Results: Among 348 patients studied, 43 (12.4%) developed complications requiring re-exploration. Lower preoperative albumin levels significantly increased the risk of complications (OR 2.45, 95% CI 1.12–5.35), especially in older and previously irradiated patients. Causal mediation analysis revealed that these complications explained 11.4% of the effect on increased hospitalization costs, after controlling for confounders. Conclusions: Lower preoperative albumin levels in HPC patients are associated with a higher risk of microvascular free flap complications and elevated healthcare costs, underscoring the need for enhanced nutritional support before surgery in this population. Level of evidence: 3. [ABSTRACT FROM AUTHOR]

Tumor immunotherapies targeting PD-(L)1 exhibit anti-tumor efficacy in only 10–30% of patients with various cancers. Literature has demonstrated that a "hot tumor" which contains high T lymphocytes in the tumor microenvironment exhibits a better response to immunotherapies than a "cold tumor." This study aimed to investigate whether tumor-intrinsic IFNα and CXCL10 determine the recruitment and activation of CD8+ T cells to become "hot tumor." In this study, we found that CXCL10 overexpressed in a variety of tumors including lung, colon, and liver tumors with a correlation with PD-L1. High PD-L1 and CXCL10 are associated with better survival rates in tumor patients receiving immunotherapies. IFNs-downstream transcriptional factor IRF-1 and STAT1 were correlated with PD-L1 and CXCL10 expression. We demonstrated that IRF-1 and STAT1 were both bound with the promoters of PD-L1 and CXCL10, sharing the same signaling pathway and determining IFNs-mediated PD-L1 and CXCL10 expression. In addition, IFNα significantly increased activation marker IFNγ in PBMCs, promoting M1 type monocyte differentiation, CD4+ T, and CD8+ T cell activation. Particularly, we found that CD8+ T lymphocytes abundantly expressed CXCR3, a receptor of CXCL10, by flow cytometry, indicating that tumor-intrinsic CXCL10 potentially recruited CD8+ T in tumor microenvironment. To demonstrate the hypothesis, immunotherapy-sensitive CT26 and immunotherapy-resistant LL/2 were used and we found that CT26 cells exhibited higher IFNα, IFNγ, CXCL10, and PD-L1 levels compared to LL/2, leading to higher IFNγ expression in mouse splenocytes. Moreover, we found that CD8+ T cells were recruited by CXCL10 in vitro, whereas SCH546738, an inhibitor of CXCR3, inhibited T cell migration and splenocytes-mediated anti-tumor effect. We then confirmed that CT26-derived tumor was sensitive to αPD-L1 immunotherapy and LL/2-tumor was resistant, whereas αPD-L1 significantly increased T lymphocyte activation marker CD107a in CT26-derived BALB/c mice. In conclusion, this study revealed that CXCL10 expression is correlated with PD-L1 in tumors, sharing the same signaling pathway and associating with better immunotherapeutic efficacy. Further evidence in the syngeneic tumor models demonstrated that immunotherapy-sensitive CT26 intrinsically exhibited higher IFNα and CXCL10 compared to immunotherapy-resistant LL/2 to recruit and activate CD8+ T cells in the tumor microenvironment, exhibiting "hot tumor" characteristic of sensitizing αPD-L1 immunotherapies. [ABSTRACT FROM AUTHOR]

The growing number of older people has become a critical social and economic challenge globally. In Taiwan, the proportion of people aged 65 and over had exceed 14% since 2018 and the Taiwan government plans to develop housing communities for the growing population of older adults, but the public's preferences for senior housing are diversified and require further consideration. This study constructed a conceptual framework based on the choice experiment approach from social, physical and management dimensions. Five assessing attributes and one price attribute regarding senior housing were included and recombined to generate various choice alternatives. These choice alternatives were then incorporated into questionnaires to further examine respondents' preferences and willingness to pay toward senior housing construction using random parameter logit (RPL) and latent class model (LCM). We found that respondents preferred professional care service the most, followed by the inclusion of family rooms, accessible housing, and various security measures by RPL model. Using LCM analysis, this study further identified that respondents who were younger, highly educated, had older family members, and had previous experience with senior housing had stronger preferences for attributes such as professional care, convenient transportation, security, family rooms, accessible facilities and intergenerational housing. Our findings reinforce the significance of including professional care, security option, and family room for senior housing. These results can be references for authorities when planning the senior housing sector and developing senior housing welfare policy. [ABSTRACT FROM AUTHOR]

Background: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. Objective: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. Methods: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. Results: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. Conclusions: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021). [ABSTRACT FROM AUTHOR]

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During neuronal pruning, phagocytes engulf shed cellular debris to avoid inflammation and maintain tissue homeostasis. How phagocytic receptors recognize degenerating neurites had been unclear. Here, we identify two glucosyltransferases Alg8 and Alg10 of the N-glycosylation pathway required for dendrite fragmentation and clearance through genetic screen. The scavenger receptor Draper (Drpr) is N-glycosylated with complex- or hybrid-type N-glycans that interact specifically with galectins. We also identify the galectins Crouching tiger (Ctg) and Hidden dragon (Hdg) that interact with N-glycosylated Drpr and function in dendrite pruning via the Drpr pathway. Ctg and Hdg are required in hemocytes for expression and function, and are induced during dendrite injury to localize to injured dendrites through specific interaction with exposed phosphatidylserine (PS) on the surface membrane of injured dendrites. Thus, the galectins Ctg and Hdg bridge the interaction between PS and N-glycosylated Drpr, leading to the activation of phagocytosis.How Draper activates phagocytosis is not well understood. Here, the authors show that two Drosophila galectins, Hdg and Ctg, are secreted from hemocytes after dendrite injury and bridge phosphatidylserine and Draper to active phagocytosis. [ABSTRACT FROM AUTHOR]

Soft-matter-based photonic crystals like blue-phase liquid crystals (BPLC) have potential applications in wide-ranging photonic and bio-chemical systems. To date, however, there are limitations in the fabrication of large monocrystalline BPLCs. Traditional crystal-growth process involves the transition from a high-temperature disordered phase to an ordered (blue) phase and is generally slow (takes hours) with limited achievable lattice structures, and efforts to improve molecular alignment through post-crystallization field application typically prove ineffective. Here we report a systematic study on the molecular self-assembly dynamics of BPLC starting from a highly ordered phase in which all molecules are unidirectionally aligned by a strong electric field. We have discovered that, near the high-temperature end of the blue phase, if the applied field strength is then switched to an intermediate level or simply turned off, large-area monocrystalline BPLCs of various symmetries (tetragonal, orthorhombic, cubic) can be formed in minutes. Subsequent temperature tuning of the single crystal at a fixed applied field allows access to different lattice parameters and the formation of never-before-seen monoclinic structures. The formed crystals remain stable upon field removal. The diversity of stable monocrystalline BPLCs with widely tunable crystalline symmetries, band structures, and optical dispersions will significantly improve and expand their application potentials. Soft-matter-based photonic crystals like blue-phase liquid crystals (BPLC) have potential applications but face fabrication limitations for large monocrystalline structures. The authors report a method to rapidly form large-area monocrystalline BPLCs with various symmetries and tunable properties through an application of electric fields and temperature control. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is associated with cardiac conduction defects and is a strong risk factor for heart failure. Complete left bundle branch block (cLBBB), a cardiac conduction abnormality, may have an unfavorable effect on ventricular mechanical synchrony and lead to the progression of heart failure. Once heart failure develops, it seems to act together with underlying CKD in a vicious circle. Therefore, this study aimed to explore the influence of CKD in patients with cLBBB by assessing the estimated glomerular filtration rate (eGFR). We examined a hospital-based sample of 416 adult patients with cLBBB from 2010 to 2013. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cox proportional hazard models were used to estimate the hazard ratio for all-cause mortality and cardiovascular mortality. A total of 416 adult patients with a mean age of 71 ± 13 years were enrolled. The median follow-up period was 3.6 years. After adjusting for clinical, electrocardiographic parameters, and medication use, cox regression analysis showed that total mortality was significantly associated with older age (Hazard Ratio (HR) = 1.03, 95% CI = 1.01–1.05, p = 0.002), presence of congestive heart failure (HR = 2.39, 95% CI = 1.63–3.49, p < 0.001), advanced CKD (HR = 2.48, 95% CI = 1.71–3.59, p < 0.001), higher HR (HR = 1.02, 95% CI = 1.01–1.03, p < 0.001) and without use of ACEI/ARB (HR = 0.59, 95% CI = 0.41–0.85, p = 0.005) were independent predictors of the total mortality. Multivariate Cox hazard regression analysis demonstrated that, in comparison to patients lacking cLBBB, the coexistence of CKD (eGFR < 60 mL/min/1.73 m2) among those with LBBB significantly heightened the risks of both total mortality (HR ratio of 5.01 vs. 2.40) and CV death (HR ratio of 61.78 vs. 14.41) even following adjustment for clinical covariates and ECG parameters. In summary, within patients exhibiting cLBBB, the presence of CKD serves as a significant risk factor for all-cause mortality. [ABSTRACT FROM AUTHOR]

Objective: The impact of acupuncture and moxibustion on postoperative complications and adverse events (AEs) of chemotherapy in patients with gastric cancer (GC) has been investigated. Through a meta-analysis of existing randomized controlled trials (RCTs), this study sought to strengthen the evidentiary basis to help investigators further understand the effects of moxibustion and acupuncture on postoperative complications and AEs of chemotherapy among GC patients. Methods: Embase, Web of Science, PubMed, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database for Chinese Technical Periodicals were searched to collect RCTs on effects of acupuncture and moxibustion on gastrointestinal function and AEs among GC patients undergoing surgery and chemotherapy. Outcome measures included postoperative gastrointestinal recovery (bowel sound recovery time, time to first flatus/defecation/feeding), the incidence of AEs (nausea and vomiting, abdominal distension, and diarrhea), myelosuppression (white blood cells, hemoglobin, and platelet), and immune function indicators (CD3+ and CD4+). To assess quality, the Cochrane Risk of Bias Tool was utilized. Review Manager 5.4 was implemented to do the meta-analysis. Results: Fifteen eligible RCTs involved 1259 patients. Meta-analysis results showed that the experimental group had a significantly shorter bowel sound recovery time (MD = − 14.57, 95% CI = [− 18.97, − 10.18], P < 0.00001), time to first flatus (MD = − 17.56, 95% CI = [− 22.23, − 12.88], P < 0.00001), time to first defecation (MD = − 17.05, 95% CI = [− 21.02, − 13.09], P < 0.00001), and time to first feeding (MD = − 23.49, 95% CI = [− 28.81, − 18.17], P < 0.00001) than the control group. There were significant decreases in the incidence of nausea and vomiting (RR = 0.46, 95% CI = [0.21, 1.02], P = 0.05) and abdominal distension (RR = 0.45, 95% CI = [0.27, 0.75], P = 0.002) observed in the experimental group in comparison with the control group. The experimental group demonstrated a significant increase in white blood cell counts in comparison with to the control group (MD = 0.89, 95% CI = [0.23, 1.55], P = 0.008). The experimental group showed significantly higher levels of CD3+ (MD = 7.30, 95% CI = [1.86, 12.74], P = 0.009) and CD4+ (MD = 2.75, 95% CI = [1.61, 3.90], P < 0.00001) than the control group. Conclusion: Among GC patients, acupuncture and moxibustion can aid in gastrointestinal function recovery, reduce the incidence of AEs of surgery and chemotherapy, and improve immune function. [ABSTRACT FROM AUTHOR]

Introduction: Generalized pustular psoriasis (GPP) is a rare and severe psoriasis subtype characterized by the rapid onset of coalescing sterile pustules over broad body areas and systemic inflammation. Data on its clinical course and outcomes in Taiwan are limited. We evaluated the clinical profile and outcomes of patients with GPP flares in Taiwan. Methods: This retrospective analysis included adult patients with moderate-to-severe GPP flares occurring in January 2008–December 2021. Data were extracted from medical charts and electronic health records in the Chang Gung Research Database. Statistical analyses were performed using SAS for Windows (version 9.4). Multivariate Poisson regression models were built to investigate different predictors of GPP flare rate. Results: Thirty-four patients with 81 moderate-to-severe GPP flares were identified. Of the 14 patients undergoing genetic analysis, 10 (71.4%) had an IL36RN mutation. Patients' mean age at the index GPP flare was 47.1 ± 16.5 years; 58.0% of the flares were severe, while 42.0% were moderate. Overall, 96.3% of GPP flares were treated with at least one systemic therapy, acitretin being the most prescribed (85.2%), followed by cyclosporine (45.7%) and methotrexate (18.5%). After treatment, the proportion of flares responding positively increased from 0% on day 2 to 6.2% by week 12. Patients were newly diagnosed with psoriasis (23.5%), hypertension (20.6%), diabetes mellitus (14.7%), psoriatic arthritis (2.9%), malignant tumor (8.8%), and depression/anxiety (2.9%) after enrollment. Complications occurring within 12 weeks of GPP flares included arthritis (25.9% of the flares), skin infection (8.6%), and other infections (2.5%). No fatalities were reported. In the multivariate model, former smokers, patients with hepatic disease, and patients with psoriatic arthritis had an increased GPP rate ratio (RR) of 13.33 (95% confidence interval, CI, 2.87–61.78), 14.08 (95% CI 3.04–65.29), and 34.84 (95% CI 4.77- 254.42), respectively. Contrarily, obese and rheumatoid arthritis patients had a lower GPP rate ratio of 0.21 (95% CI 0.08–0.54) and 0.07 (95% CI 0.006–0.78), respectively. Conclusions: Our findings highlight the complexity of GPP flare presentations and the need for individualized, patient-centered management approaches and continued research to improve affected individuals' care and outcomes. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) stands as the second most prevalent hematological malignancy, constituting approximately 10% of all hematological malignancies. Current guidelines recommend upfront autologous stem cell transplantation (ASCT) for transplant-eligible MM patients. This study seeks to delineate factors influencing post–ASCT outcomes in MM patients. Our cohort comprised 150 MM patients from Taipei Veterans General Hospital, with progression-free survival (PFS) as the primary endpoint and overall survival (OS) as the secondary endpoint. A Cox proportional hazards model was employed to discern potential predictive factors for survival. ASCT age ≥ 65 (hazard ratio [HR] 1.94, 95% confidence interval [CI] 1.08–3.47) and the presence of extramedullary disease (HR 2.53, 95% CI 1.53–4.19) negatively impacted PFS. Conversely, treatment response ≥ VGPR before ASCT (HR 0.52, 95% CI 0.31–0.87) and total CD34+ cells collected ≥ 4 × 106 cells/kg on the first stem cell harvesting (HR 0.52, 95% CI 0.32–0.87) were positively associated with PFS. For OS, patients with ISS stage III (HR 2.06, 95% CI 1.05–4.04), the presence of extramedullary disease (HR 3.92, 95% CI 2.03–7.58), light chain ratio ≥ 100 before ASCT (HR 7.08, 95% CI 1.45–34.59), post–ASCT cytomegalovirus infection (HR 9.43, 95% CI 3.09–28.84), and a lower conditioning melphalan dose (< 140 mg/m2; HR 2.75, 95% CI 1.23–6.17) experienced shorter OS. In contrast, post–ASCT day + 15 absolute monocyte counts (D15 AMC) > 500/µl (HR 0.36, 95% CI 0.17–0.79) and post–ASCT day + 15 platelet counts (D15 PLT) > 80,000/µl (HR 0.48, 95% CI 0.24–0.94) were correlated with improved OS. Significantly, early PLT and AMC recovery on day + 15 predicting longer OS represents a novel finding not previously reported. Other factors also align with previous studies. Our study provides real-world insights for post–ASCT outcome prediction beyond clinical trials. [ABSTRACT FROM AUTHOR]

Whether brain stimulation could modulate brain structure in autism remains unknown. This study explored the impact of continuous theta burst stimulation (cTBS) over the left dorsolateral prefrontal cortex (DLPFC) on white matter macro/microstructure in intellectually able children and emerging adults with autism. Sixty autistic participants were randomized (30 active) and received active or sham cTBS for eight weeks twice per week, 16 total sessions using a double-blind (participant-, rater-, analyst-blinded) design. All participants received high-angular resolution diffusion MR imaging at baseline and week 8. Twenty-eight participants in the active group and twenty-seven in the sham group with good imaging quality entered the final analysis. With longitudinal fixel-based analysis and network-based statistics, we found no significant difference between the active and sham groups in changes of white matter macro/microstructure and connections following cTBS. In addition, we found no association between baseline white matter macro/microstructure and autistic symptom changes from baseline to week 8 in the active group. In conclusion, we did not find a significant impact of left DLPFC cTBS on white matter macro/microstructure and connections in children and emerging adults with autism. These findings need to be interpreted in the context that the current intellectually able cohort in a single university hospital site limits the generalizability. Future studies are required to investigate if higher stimulation intensities and/or doses, other personal factors, or rTMS parameters might confer significant brain structural changes visible on MRI in ASD. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is the most common autoimmune disorder characterized by decreased platelet counts and impaired platelet production. Eltrombopag has been demonstrated to be safe and effective for children with ITP. It is reported eltrombopag can achieve a sustained response off treatment. However, data on its overall efficacy and safety profile are scarce in children. This study aimed to investigate the long-term efficacy of eltrombopag in children with ITP. Treatment overall response (OR), complete response (CR), response (R), durable response (DR), no response (NR), treatment free remission (TFR), and relapse rate, were assessed in 103 children with ITP during eltrombopag therapy. The OR rate, CR rate, R rate, DR rate, NR rate, TFR rate, and relapse rate were 67.0%, 55.3%, 11.7%, 56.3%, 33.0%, 60%, 36.2%, respectively. Importantly, we discovered that newly diagnosed ITP patients showed a higher DR rate, TFR rate and lower relapse rate compared to persistent and chronic ITP patients. Furthermore, the CR rate, DR rate, and TFR rate of 5 patients under six months were 100%. None of them suffered relapse. The most common adverse event (AEs) was hepatotoxicity (7.77%). Our study highlighted the critical role of eltrombopag as the second-line treatment in children with ITP who were intolerant to first-line therapy. [ABSTRACT FROM AUTHOR]

Tofacitinib is the first oral JAK inhibitor approved for treating rheumatoid arthritis (RA). To enhance our understanding of tofacitinib drug response, we used hierarchical clustering to analyse the profiles of patient who responded to the treatment in a real-world setting. Patients who commenced on tofacitinib treatment were selected from 12 major rheumatology centres in Malaysia. The aim was to assess their response to tofacitinib defined as achieving DAS28-CRP/ESR ≤ 3.2 and DAS28 improvement > 1.2 at 12 weeks. A hierarchical clustering analysis was performed using sociodemographic and clinical parameters at baseline. All 163 RA patients were divided into three clusters (Clusters 1, 2 and 3) based on specific clinical factors at baseline including bone erosion, antibody positivity, disease activity and anaemia status. Cluster 1 consisted of RA patients without bone erosion, antibody negative, low baseline disease activity measure and absence of anaemia. Cluster 2 comprised of patients without bone erosion, RF positivity, anti-CCP negativity, moderate to high baseline disease activity score and absence of anaemia. Cluster 3 patients had bone erosion, antibody positivity, high baseline disease activity and anaemia. The response rates to tofacitinib varied among the clusters: Cluster 1 had a 79% response rate, Cluster 2 had a 66% response rate, and Cluster 3 had a 36% response rate. The differences in response rates between the three clusters were found to be statistically significant. This cluster analysis study indicates that patients who are seronegative and have low disease activity, absence of bone erosion and no signs of anaemia may have a higher likelihood of benefiting from tofacitinib therapy. By identifying clinical profiles that respond to tofacitinib treatment, we can improve treatment stratification yielding significant benefits and better health outcomes for individuals with RA. [ABSTRACT FROM AUTHOR]

Limited data exist on long-term renal outcomes in patients with hyperglycemic crisis (HC) as initial type 2 diabetes presentation. We evaluated the risk of chronic kidney disease (CKD) development in those with concurrent HC at diagnosis. Utilizing Taiwan's insurance claims from adults newly diagnosed with type 2 diabetes during 2006–2015, we created HC and matched non-HC cohorts. We assessed incident CKD/diabetic kidney disease (DKD) by 2018's end, calculating the hazard ratio (HR) with the Cox model. Each cohort comprised 13,242 patients. The combined CKD and DKD incidence was two-fold higher in the HC cohort than in the non-HC cohort (56.47 versus 28.49 per 1000 person-years) with an adjusted HR (aHR) of 2.00 (95% confidence interval [CI] 1.91–2.10]). Risk increased from diabetic ketoacidosis (DKA) (aHR:1.69 [95% CI 1.59–1.79]) to hyperglycemic hyperosmolar state (HHS) (aHR:2.47 [95% CI 2.33–2.63]) and further to combined DKA-HHS (aHR:2.60 [95% CI 2.29–2.95]). Subgroup analysis in individuals aged ≥ 40 years revealed a similar trend with slightly reduced incidences and HRs. Patients with HC as their initial type 2 diabetes presentation face a higher CKD risk than do those without HC. Enhanced medical attention and customized interventions are crucial to reduce this risk. [ABSTRACT FROM AUTHOR]

Three Gram-stain-positive bacterial strains were isolated from traditional Chinese pickle and characterized using a polyphasic taxonomic approach. Results of 16S rRNA gene sequence analysis indicated that strain 74-4T was most closely related to the type strains of Lacticaseibacillus suibinensis and Lacticaseibacillus suilingensis, having 99.9% and 100% 16S rRNA gene sequence similarities, respectively, and that strains 419-1.2T and 262-4 were most closely related to the type strains of Companilactobacillus heilongjiangensis, Companilactobacillus nantensis, Companilactobacillus huachuanensis, and Companilactobacillus nuruki, having 98.5–99.7% 16S rRNA gene sequence similarities. The phylogenomic trees indicated that strain 74-4T was related to the type strains of L. suibinensis and L. suilingensis, and that strains 419-1.2T and 262-4 were related to the type strains of C. heilongjiangensis, C. nantensis, C. huachuanensis, and Companilactobacillus zhachilii. The ANI and dDDH values between strain 74-4T and type strains of phylogenetically related species were less than 92.7% and 49.9%, respectively. The ANI and dDDH values between strains 419-1.2T and 262-4 and type strains of phylogenetically related species were less than 93.4% and 51.7%, respectively. Based upon the data of polyphasic characterization obtained in the present study, two novel species, Lacticaseibacillus salsurivasis sp. nov. and Companilactobacillus muriivasis sp. nov., are proposed and the type strains are 74-4T (= JCM 35890T = CCTCC AB 2022414T) and 419-1.2T (= JCM 35891T = CCTCC AB 2022413T), respectively. [ABSTRACT FROM AUTHOR]

In 2018, Nouioui et al. proposed that Bifidobacterium coryneforme was a later synonym of Bifidobacterium indicum on the basis of the digital DNA-DNA hybridization (dDDH) value (85.0%) between B. coryneforme LMG 18911T and B. indicum LMG 11587T. However, in the study of Scardovi et al. (1970), the type strains of B. indicum and B. coryneforme only exhibited 60% DNA-DNA hybridization value. In the present study, the genomes of B. coryneforme CGMCC 1.2279T, B. coryneforme JCM 5819T, B. indicum JCM 1302T, B. indicum CGMCC 1.2275T, B. indicum DSM 20214T, B. indicum LMG 27437T, B. indicum ATCC 25912T, B. indicum KCTC 3230T, B. indicum CCUG 34985T, were sequenced, and the taxonomic relationship between B. coryneforme and B. indicum was re-evaluated. On the basis of the results presented here, (i) ATCC 25912 and DSM 20214 deposited by Vittorio Scardovi are two different strains; (ii) the type strain of B. indicum is ATCC 25912T (= JCM 1302T = LMG 27437T = CGMCC 1.2275T = KCTC 3230T), and not DSM 20214 (= BCRC 14674 = CCUG 34985 = LMG 11587); (iii) B. coryneforme and B. indicum represent two different species of the genus Bifidobacterium; (iv) strain DSM 20214 (= BCRC 14674 = CCUG 34985 = LMG 11587) belongs to B. coryneforme. [ABSTRACT FROM AUTHOR]

Purpose: To study the effectiveness of federated learning in in vitro fertilization on embryo evaluation tasks. Methods: This is a retrospective cohort analysis. Two datasets were used in this study. The ploidy status dataset consisted of 10,065 embryo records, 3760 treatments, and 2479 infertile couples from 5 hospitals. The clinical pregnancy dataset consisted of 4495 embryo records, 4495 treatments, and 3704 infertile couples from 4 hospitals. Federated learning and the gradient boosting decision tree algorithm were utilized for modeling. Results: On the ploidy status dataset, the areas under the receiver operating characteristic curves of our model trained with federated learning were 71.78%, 73.10%, 69.39%, 69.72%, and 73.46% for 5 hospitals respectively, showing an average increase of 2.5% compared to those of our model trained without federated learning. On the clinical pregnancy dataset, the areas under the receiver operating characteristic curves of our model trained with federated learning were 72.03%, 56.77%, 61.63%, and 58.58% for 4 hospitals respectively, showing an average increase of 3.08%. Conclusions: Federated learning can improve data privacy and data security and meanwhile improve the performance of embryo selection tasks by leveraging data from multiple sources. This study demonstrates the effectiveness of federated learning in embryo evaluation, and the results show the promise for future application. [ABSTRACT FROM AUTHOR]

Stimulated by the recent experimental results on the fully-charm tetraquark states, we systematically calculate the mass spectra of the fully-charm tetraquark states in 8 [ c c ¯ ] ⊗ 8 [ c c ¯ ] color configuration via QCD sum rules. By constructing nine 8 [ c c ¯ ] ⊗ 8 [ c c ¯ ] type currents with quantum numbers J PC = 0 - + , 0 - - , 1 - + , 1 + - , 1 - - and 2 + + , we perform analytic calculation up to dimension six in the operator product expansion (OPE). We find the fully-charm tetraquark states with J PC = 1 + - , 2 + + lie around 6.48 ∼ 6.62 GeV while the fully-charm tetraquark states with J PC = 0 - + , 0 - - , 1 - - , 1 - + are about 6.85 ∼ 7.02 GeV. Notably, the mass predictions for the c c ¯ c c ¯ tetraquarks, specifically those with J PC = 2 + + , align with the broad structure identified by LHCb. Moreover, the masses of fully-charm tetraquarks with J PC = 0 - + and 1 - + are anticipated to match closely with the mass of X(6900), considering the margin of error. Such findings hint at the presence of some 8 [ c c ¯ ] ⊗ 8 [ c c ¯ ] components within the di- J / ψ structures observed by LHCb. The predictions for tetraquark states with J PC = 0 - - , 1 + - , 1 - - may be accessible in the future BelleII, Super-B, PANDA, and LHCb experiments. [ABSTRACT FROM AUTHOR]

3-Bromofluoranthene (3-BrFlu) is the secondary metabolite of fluoranthene, which is classified as a polycyclic aromatic hydrocarbon, through bromination and exists in the fine particulate matter of air pollutants. Endothelial dysfunction plays a critical role in the pathogenesis of cardiovascular and vascular diseases. Little is known about the molecular mechanism of 3-BrFlu on endothelial dysfunction in vivo and in vitro assay. In the present study, 3-BrFlu included concentration-dependent changes in ectopic angiogenesis of the sub-intestinal vein and dilation of the dorsal aorta in zebrafish. Disruption of vascular endothelial integrity and up-regulation of vascular endothelial permeability were also induced by 3-BrFlu in a concentration-dependent manner through pro-inflammatory responses in vascular endothelial cells, namely, SVEC4-10 cells. Generation of pro-inflammatory mediator PGE2 was induced by 3-BrFlu through COX2 expression. Expression of COX2 and generation of pro-inflammatory cytokines, including TNFα and IL-6, were induced by 3-BrFlu through phosphorylation of NF-κB p65, which was mediated by phosphorylation of MAPK, including p38 MAPK, ERK and JNK. Furthermore, generation of intracellular ROS was induced by 3-BrFlu, which is associated with the down-regulated activities of the antioxidant enzyme (AOE), including SOD and catalase. We also found that 3-BrFlu up-regulated expression of the AOE and HO-1 induced by 3-BrFlu through Nrf-2 expression. However, the 3-BrFlu-induced upregulation of AOE and HO-1 expression could not be revised the responses of vascular endothelial dysfunction. In conclusion, 3-BrFlu is a hazardous substance that results in vascular endothelial dysfunction through the MAPK-mediated-NFκB pro-inflammatory pathway and intracellular ROS generation. [ABSTRACT FROM AUTHOR]

Since long-term exposure to PM2.5 is a growing concern in Taiwan, therefore, our study aimed to investigate the association between different PM2.5 concentrations and cause-specific mortalities, as well as explore the influence of demographic, socio-economic, and geographic determinants on mortality. Utilizing a Distributed Lag Non-Linear Model (DLNM), we estimated the PM2.5-attributable mortality burden among the elderly population (above 65 years) in Taiwan from 2005 to 2018. Our analysis considered various thresholds defined by the World Health Organization (WHO) to assess the impact of PM2.5 concentrations, ranging from standard Air Quality Guidelines (AQG) levels (0–15 μg/m3) to higher interim targets (up to 80 μg/m3). Our study reveals that achieving AQG levels (< 15 μg/m3) in Taiwan could potentially prevent 5571 elderly deaths, including 889 deaths from CVDs, 934 deaths from RTIs, and 680 deaths from chronic diseases. We observed a rapid increase in attributable deaths at lower PM2.5 concentrations, with a subsequent marginal increase at higher levels of exposure. We also identified several factors that modify the effects of PM2.5 exposures among elderly. For example, we found that higher elderly population ratios and high-income households were associated with an elevated risk of PM2.5-related deaths. In contrast, higher social welfare expenditure, better availability of medical practitioners per square kilometer, and higher forest-to-land ratios were associated with positive effects, indicating their potential in reducing mortality risk. This study fills a knowledge gap by examining the health consequences of varying PM2.5 levels and explored the complex interplay between demographic, socio-economic, and geographic factors in relation to PM2.5-related mortality. [ABSTRACT FROM AUTHOR]

Purpose: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients. Methods: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients. Results: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated. Conclusion: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients. [ABSTRACT FROM AUTHOR]

Four Gram-stain-positive bacterial strains (designated 475-2T, 46-6BT, 778-2T and A810-3), isolated from traditional Chinese pickle, were characterized using a polyphasic taxonomic approach. Strain 475-2T was most closely related to the type strain of Lapidilactobacillus achengensis, having 99.9% 16S rRNA gene sequence similarity, 94.1–95.1% average nucleotide identity (ANI) and 57.6% digital DNA–DNA hybridization (dDDH) values. Strain 46-6BT was most closely related to the type strain of Secundilactobacillus similis, having 99.8% 16S rRNA gene sequence similarity, 94.3–94.9% ANI and 58.9–59.2% dDDH values. Strains 778-2T and A810-3 were phylogenetically related to the type strains of Streptococcus salivarius, Streptococcus thermophilus and Streptococcus vestibularis, having 99.7–99.9% 16S rRNA gene sequence similarities, 89.1–94.4% ANI and 39.0–55.5% dDDH values. Based upon the data obtained in the present study, three novel species, Lapidilactobacillus salsurivasis sp. nov., Secundilactobacillus muriivasis sp. nov. and Streptococcus parasalivarius sp. nov., are proposed and the type strains are 475-2T (= JCM 36613T = CCTCC AB 2023258T = LMG 33412T), 46-6BT (= JCM 36612T = CCTCC AB 2023259T = LMG 33411T) and 778-2T (= JCM 36614T = CCTCC AB 2023257T = LMG 33413T), respectively. [ABSTRACT FROM AUTHOR]

This study aims to assess the association between nicotine replacement therapy (NRT), varenicline, and untreated smoking with the risk of developing eye disorders. We employed a new-user design to investigate the association between NRT use and the incidence of eye disorders by the Taiwan National Health Insurance program. This study included 8416 smokers who received NRT and 8416 smokers who did not receive NRT (control group) matched using propensity scores between 2007 and 2018. After adjustment for relevant factors, a multivariable Cox regression analysis revealed that compared with untreated smokers, NRT use was associated with a significantly reduced risk of macular degeneration (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.13–0.87, P = 0.024). When stratified by dose, short-term NRT use (8–28 defined daily doses) was associated with significantly lower risk of glaucoma (HR: 0.35; 95% CI: 0.16–0.80, P = 0.012) and a trend toward reduced risk of cataract (HR: 0.60; 95% CI: 0.36–1.01, P = 0.053) compared to no treatment. However, these associations were not observed with long-term NRT use. The results of this real-world observational study indicate that NRT use, particularly short-term use, was associated with a lower risk of certain eye disorders compared to no treatment for smoking cessation. Long-term NRT use did not demonstrate the same benefits. Thus, short-term NRT may be a beneficial treatment strategy for reducing the risk of eye disorders in smokers attempting to quit. However, further evidence is required to verify these findings and determine the optimal duration of NRT use. [ABSTRACT FROM AUTHOR]

Bonnet polishing, which is a sub-aperture polishing method, is crucial to the production of aspherical lenses. However, sub-aperture polishing generates regular residual periodic ripples, which result in tool path ripple (TPR) error and reduce surface precision. This study investigated the effects of groove patterns in the heads used for bonnet polishing on material removal and the peak-to-valley (PV) and root-mean-square (RMS) error resulting from TPR. The effects of groove pattern (i.e., no groove, annular grooves, or radial grooves) on the tool influence function and TPR error were investigated through simulation and experimentation. Experimentally, the pad with annular grooves achieved the highest material removal rate, which was 56.3% and 14.0% higher on average than those achieved by the pads with no groove and radial grooves, respectively. However, the pad with radial grooves achieved the lowest PV (1.5834 nm) and RMS (0.7487 nm) TPR error, which were respectively 27.8% and 20.4% lower than those achieved by the pad with no groove and 43.3% and 46.0% lower than those achieved by the pad with annular grooves. In summary, annular grooves enhance material removal, and radial grooves improve surface quality. [ABSTRACT FROM AUTHOR]

This study investigated the healthcare utilization and medical expenditure of type 2 diabetes mellitus (T2DM) patients with generalized anxiety disorder (GAD) and identified the associated factors. The healthcare utilization and expenditure of T2DM patients with (case group) and without (control group) GAD between 2002 and 2013 were examined using the population-based Taiwan National Health Insurance Research Database. Healthcare utilization included outpatient visits and hospitalization; health expenditure included outpatient, inpatient, and total medical expenditure. Moreover, nonpsychiatric healthcare utilization and medical expenditure were distinguished from total healthcare utilization and medical expenditure. The average healthcare utilization, including outpatient visits and hospitalization, was significantly higher for the case group than for the control group (total and nonpsychiatric). The results regarding differences in average outpatient expenditure (total and nonpsychiatric), inpatient expenditure (total and nonpsychiatric), and total expenditure (total and nonpsychiatric) between the case and control groups are inconsistent. Sex, age, income, comorbidities/complications, and the diabetes mellitus complication severity index were significantly associated with outpatient visits, medical expenditure, and hospitalization in the case group (total and nonpsychiatric). Greater knowledge of factors affecting healthcare utilization and expenditure in comorbid individuals may help healthcare providers intervene to improve patient management and possibly reduce the healthcare burden in the future. [ABSTRACT FROM AUTHOR]

Diabetic cognitive impairment is a common complication in type 2 diabetes. Berberine (BBR) is an isoquinoline alkaloid that has been shown to have neuroprotective effects against diabetes. This study aimed to investigate the effect of BBR on the gray and white matter of the brain by using magnetic resonance imaging (MRI) and to explore the underlying mechanisms. The study used diabetic db/db mice and administered BBR (50 and 100 mg/kg) intragastrically for twelve weeks. Morris water maze was applied to examine cognitive function. T2-weighted imaging (T2WI) was performed to assess brain atrophy, and diffusion tensor imaging (DTI) combined with fiber tracking was conducted to monitor the structural integrity of the white matter, followed by histological immunostaining. Furthermore, the protein expressions of the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT)/ glycogen synthase kinase-3β (GSK-3β) were detected. The results revealed that BBR significantly improved the spatial learning and memory of the db/db mice. T2WI exhibited ameliorated brain atrophy in the BBR-treated db/db mice, as evidenced by reduced ventricular volume accompanied by increased hippocampal volumes. DTI combined with fiber tracking revealed that BBR increased FA, fiber density and length in the corpus callosum/external capsule of the db/db mice. These imaging findings were confirmed by histological immunostaining. Notably, BBR significantly enhanced the protein levels of phosphorylated AKT at Ser473 and GSK-3β at Ser9. Collectively, this study demonstrated that BBR significantly improved the cognitive function of the diabetic db/db mice through ameliorating brain atrophy and promoting white matter reorganization via AKT/GSK-3β pathway. [ABSTRACT FROM AUTHOR]

Objectives: Transcranial sonography has been used as a valid neuroimaging tool to diagnose Parkinson's disease (PD). This study aimed to develop a modified transcranial sonography (TCS) technique based on a deep convolutional neural network (DCNN) model to predict Parkinson's disease. Methods: This retrospective diagnostic study was conducted using 1529 transcranial sonography images collected from 854 patients with PD and 775 normal controls admitted to the Second Affiliated Hospital of Soochow University (Suzhou, Jiangsu, China) between September 2019 and May 2022. The data set was divided into training cohorts (570 PD patients and 541 normal controls), and the validation set (184 PD patients and 234 normal controls). Using these datasets, we developed four different DCNN models (ResNet18, ResNet50, ResNet152, and DenseNet121). We then assessed their diagnostic performance, including the area under the receiver operating characteristic (AUROC) curve, specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and F1 score and compared with traditional diagnostic criteria. Results: Among the 1529 TCS images, 570 PD patients and 541 normal controls from 4 of 6 sonographers of the TCS team were selected as the training cohort, and 184 PD patients and 234 normal controls from the other 2 sonographers were chosen as the validation cohort. There were no sex and age differences between PD patients and normal control subjects in the training and validation cohorts (P values > 0.05). All DCNN models achieved good performance in distinguishing PD patients from normal control subjects on the validation datasets, with diagnostic AUROCs and accuracy of 0.949 (95% CI 0.925, 0.965) and 86.60 for the RestNet18 model, 0.949 (95% CI 0.929, 0.971) and 87.56 for ResNet50, 0.945 (95% CI 0.931, 0.969) and 88.04 for ResNet152, 0.953 (95% CI 0.935, 0.971) and 87.80 for DenseNet121, respectively. On the other hand, the diagnostic accuracy of the traditional diagnostic method was 82.30. The accuracy of all DCNN models was higher than that of traditional diagnostic method. Moreover, the 5k-fold cross-validation results in train datasets showed that these DCNN models are robust. Conclusion: The developed transcranial sonography-based DCNN models performed better than traditional diagnostic criteria, thus improving the sonographer's accuracy in diagnosing PD. [ABSTRACT FROM AUTHOR]

Main conclusion: CsNAC086 was found to promote the expression of CsFLS, thus promoting the accumulation of flavonols in Camellia sinensis. Flavonols, the main flavonoids in tea plants, play an important role in the taste and quality of tea. In this study, a NAC TF gene CsNAC086 was isolated from tea plants and confirmed its regulatory role in the expression of flavonol synthase which is a key gene involved in the biosynthesis of flavonols in tea plant. Yeast transcription-activity assays showed that CsNAC086 has self-activation activity. The transcriptional activator domain of CsNAC086 is located in the non-conserved C-terminal region (positions 171–550), while the conserved NAC domain (positions 1–170) does not have self-activation activity. Silencing the CsNAC086 gene using antisense oligonucleotides significantly decreased the expression of CsFLS. As a result, the concentration of flavonols decreased significantly. In overexpressing CsNAC086 tobacco leaves, the expression of NtFLS was significantly increased. Compared with wild-type tobacco, the flavonols concentration increased. Yeast one-hybrid assays showed CsNAC086 did not directly regulate the gene expression of CsFLS. These findings indicate that CsNAC086 plays a role in regulating flavonols biosynthesis in tea plants, which has important implications for selecting and breeding of high-flavonols-concentration containing tea-plant cultivars. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to raise awareness of the disparities in survival predictions among races in head and neck cancer (HNC) patients by developing and validating population-based prognostic models specifically tailored for Taiwanese and Asian populations. Methods: A total of 49,137 patients diagnosed with HNCs were included from the Taiwan Cancer Registry (TCR). Six prognostic models, divided into three categories based on surgical status, were developed to predict both overall survival (OS) and cancer-specific survival using the registered demographic and clinicopathological characteristics in the Cox proportional hazards model. The prognostic models underwent internal evaluation through a tenfold cross-validation among the TCR Taiwanese datasets and external validation across three primary racial populations using the Surveillance, Epidemiology, and End Results database. Predictive performance was assessed using discrimination analysis employing Harrell's c-index and calibration analysis with proportion tests. Results: The TCR training and testing datasets demonstrated stable and favorable predictive performance, with all Harrell's c-index values ≥ 0.7 and almost all differences in proportion between the predicted and observed mortality being < 5%. In external validation, Asians exhibited the best performance compared with white and black populations, particularly in predicting OS, with all Harrell's c-index values > 0.7. Conclusions: Survival predictive disparities exist among different racial groups in HNCs. We have developed population-based prognostic models for Asians that can enhance clinical practice and treatment plans. [ABSTRACT FROM AUTHOR]

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Background: Artemisinin (ART) and its derivatives are important antimalaria agents and have received increased attention due to their broad biomedical effects, such as anticancer and anti-inflammation activities. Recently, ruthenium-derived complexes have attracted considerable attention as their anticancer potentials were observed in preclinical and clinical studies. Methods: To explore an innovative approach in colorectal cancer (CRC) management, we synthesized ruthenium–dihydroartemisinin complex (D–Ru), a novel metal-based artemisinin derivative molecule, and investigated its anticancer, anti-inflammation, and adaptive immune regulatory properties. Results: Compared with its parent compound, ART, D–Ru showed stronger antiproliferative effects on the human CRC cell lines HCT-116 and HT-29. The cancer cell inhibition of D–Ru comprised G1 cell cycle arrest via the downregulation of cyclin A and the induction of apoptosis. ART and D–Ru downregulated the expressions of pro-inflammatory cytokines IL-1β, IL-6, and IL-8. Although ART and D–Ru did not suppress Treg cell differentiation, they significantly inhibited Th1 and Th17 cell differentiation. Conclusions: Our results demonstrated that D–Ru, a novel ruthenium complexation of ART, remarkably enhanced its parent compound's anticancer action, while the anti-inflammatory potential was not compromised. The molecular mechanisms of action of D–Ru include inhibition of cancer cell growth via cell cycle arrest, induction of apoptosis, and anti-inflammation via regulation of adaptive immunity. [ABSTRACT FROM AUTHOR]

A new cyst-forming nematode, Cactodera guizhouensis n. sp., isolated from the roots and surrounding soil of potato in Guizhou, China, is the first species of genus Cactodera found from the potato rhizosphere. The new species was characterized by the L/W ratio of its cyst, being 1.4 ± 0.1 (1.3–1.8), with a fenestral diameter of 17.7–28.7 × 12.3–23.4 μm and being absent vulval denticlest; the stylet length of second stage juveniles is 26.5 ± 1.2 (24.1–29.0) μm, while the tail is 53.4 ± 3.9 (45.0–61.9) μm and the hyaline tail is 25.7 ± 2.4 (21.6–29.8) μm, the lateral field having four incisures and areolation; the eggshell having punctations. The internal transcribed spacer sequences of ribosomal RNA (ITS-rRNA), and sequences of the D2-D3 region of 28S ribosomal RNA (28S-rRNA) from the new species were amplified and sequenced. The phylogenetic tree based on the sequences showed that the new species clustered into a separate clade and could be distinguished from other species in genus Cactodera. A key to the species of Cactodera is also provided in this study. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) phononic topological insulators (TIs) featuring two-dimensional (2D) surface states and one-dimensional (1D) hinge states have opened up a new route for multi-dimensional robust wave transport, providing unprecedented methods for integrated acoustic sensors and energy harvesting devices. However, aiming at the elastic 3D phononic TI with gapless surface states and hinge states, the realization of elastic 3D phononic TIs with gapless surface states and hinge states is a significant challenge due to the complicated multi-mode polarization of elastic waves in 3D structures. In this study, we demonstrate an elastic 3D phononic TI with a Dirac hierarchy by elaborately operating the corresponding spatial symmetries of the chiral honeycomb lattice. First, a 3D double Dirac cone of elastic wave can be achieved by doubling the lattice along the out-of-plane direction to fold two iso-frequency Weyl points. The topological phase transitions and 2D gapless two-fold Dirac surface states of elastic wave are realized by breaking the half-lattice spatial translation symmetry. Subsequently, based on the Brillouin zone folding along the in-plane direction, the 2D gapless two-fold surface Dirac cones are folded into four-fold surface Dirac cones. Finally, by inducing the relative radius of adjacent holes to break the in-plane spatial inversion symmetry, the fourfold surface Dirac cones are gapped and associated with a surface state inversion, in which the gapless 1D hinge Dirac dispersion is achieved. This research offers a route for engineering the hierarchies of TIs in 3D elastic wave systems and provides new possibilities for designing 3D ultrasonic devices with unconventional functions. [ABSTRACT FROM AUTHOR]

The frequently occurring browning of plant tissue cultures is a considerable problem in causing economic losses. However, the mechanism that causes browning of plant tissues is still controvesial and technologies to effectively prevent browning of plant tissues are still scarce. In the present work, two callus lines derived from grapevine shoot tips (ST-callus) and fruit flesh (F-callus) were used to investigate the relationship between callus-associated endophytes and callus browning. We observed the transfer of browning effects from grapevine brown calli to normal calli, in a contact cocultivation experiment, then detected the emergence of endophytic bacteria from brown calli when the calli were incubated in a microbial culture medium, and the isolates were identified as genus Bacilus. The inoculation of pure cultured B. sp. strain ST-B1 into normal calli at different concentrations caused gradient callus browning, validating the callus browning-causing (CBC) endophyte. In addition, the moderate inhibition of endophytic bacteria in grapevine calli by culturing the calli in ampicillin-containing media reduced the incidence and severity of callus oxidative browning. The experiments were performed separately on two types of grapevine calli, ST-callus (derived from the tip of grapevine shoots), and F-callus (derived from the pulp of grape berries), and gave similar results. The DNA sequence amplicon approach showed that the CBC endophytic bacteria were found in both the normal and brown calli, which differed greatly in their relative abundances. And compared to the normal calli, brown calli greatly reduced the diversity of bacterial endophytes, while the diversity of fungal endophytes between normal and browning calli showed no obvious difference. The work demonstrated that callus-associated endophytes are involved in causing oxidative browning of plant cells, and suggested technologies to minimize the occurrence of the oxidative browning during plant tissue culture practices.Key message: The study revealed a mechanism by which the callus-associated endophytes are causations in triggering oxidative browning of plant cells, and the maintanence of endophytic bacterial balance is fundamental to a healthy callus. The work also suggested technologies to minimise the occurrence of browning during plant tissue culture practices. [ABSTRACT FROM AUTHOR]

Background: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. Methods: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. Results: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924–0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010–1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation. Conclusions: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. 342BNb9AdCycy4MnMisg3F Supplementary file 2 (MP4 18937 KB) [ABSTRACT FROM AUTHOR]

Background: Pancreatic neuroendocrine tumors (PNETs) with low microvessel density and fibrosis often exhibit clinical aggressiveness. Given the contribution of cancer-associated fibroblasts (CAFs) to the hypovascular fibrotic stroma in pancreatic ductal adenocarcinoma, investigating whether CAFs play a similar role in PNETs becomes imperative. In this study, we investigated the involvement of CAFs in PNETs and their effects on clinical outcomes. Methods: We examined 79 clinical PNET specimens to evaluate the number and spatial distribution of α-smooth muscle actin (SMA)–positive cells, which are indicative of CAFs. Then, the findings were correlated with clinical outcomes. In vitro and in vivo experiments were conducted to assess the effects of CAFs (isolated from clinical specimens) on PNET metastasis and growth. Additionally, the role of the stromal-cell-derived factor 1 (SDF1)–AGR2 axis in mediating communication between CAFs and PNET cells was investigated. Results: αSMA-positive and platelet-derived growth factor-α–positive CAFs were detected in the hypovascular stroma of PNET specimens. A higher abundance of α-SMA-positive CAFs within the PNET stroma was significantly associated with a higher level of clinical aggressiveness. Notably, conditioned medium from PNET cells induced an inflammatory phenotype in isolated CAFs. These CAFs promoted PNET growth and metastasis. Mechanistically, PNET cells secreted interleukin-1, which induced the secretion of SDF1 from CAFs. This cascade subsequently elevated AGR2 expression in PNETs, thereby promoting tumor growth and metastasis. The downregulation of AGR2 in PNET cells effectively suppressed the CAF-mediated promotion of PNET growth and metastasis. Conclusion: CAFs drive the growth and metastasis of aggressive PNETs. The CXCR4–SDF1 axis may be a target for antistromal therapy in the treatment of PNET. This study clarifies mechanisms underlying PNET aggressiveness and may guide future therapeutic interventions targeting the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Growing evidence has found the health protective effects of greenness exposure on tuberculosis (TB) and the impact of ambient air pollutants on TB drug-resistance. However, it remains unclear whether residential greenness is also beneficial to reduce TB drug-resistance, and whether air pollution modify the greenness-TB resistance relationship. We enrolled 5006 newly-diagnosed TB patients from Shandong, China, during 2014 to 2021. Normalized Difference Vegetation Index (NDVI) in 250 m and 500 m buffer around individuals' residential zone was used to assess greenness exposure. All patients were divided by quartiles of NDVI250-m and NDVI500-m (from low to high: Q1, Q2, Q3, Q4) respectively. Six logistic regression models (NDVI, NDVI + PM2.5/PM10/SO2/NO2/O3) were used to estimate the association of NDVI and TB drug-resistance when adjusting different air pollutants or not. All models were adjusted for age, gender, body mass index, complications, smoking, drinking, population density, nighttime light index, road density. Compared with participants in NDVI250-m Q1 and NDVI500-m Q1, other groups had lower rates of MDR-TB, PDR-TB, RFP-resistance, SM-resistance, RFP + SM resistance, INH + RFP + EMB + SM resistance. NDVI500-m reduced the risk of multidrug resistant tuberculosis (MDR-TB) and the adjusted odds ratio (aOR, 95% confidence interval, CI) compared with NDVI500-m Q1 were 0.736 (0.547–0.991) in NDVI + PM10 model, 0.733 (0.544–0.986) in NDVI + PM2.5 model, 0.735(0.546–0.99) in NDVI + SO2 model, 0.736 (0.546–0.991) in NDVI + NO2 model, respectively, P < 0.05. NDVI500-m contributed to a decreased risk of streptomycin (SM)-resistance. The aOR of rifampicin (RFP) + SM resistance were 0.132 (NDVI250-m, Q4 vs Q1, 95% CI: 0.03–0.578), 0.199 (NDVI500-m, Q3 vs. Q1, 95% CI: 0.057–0.688) and 0.264 (NDVI500-m, Q4 vs. Q1, 95% CI: 0.087–0.799). The adjusted ORs (Q2 vs. Q1, 95% CI) of isoniazid (INH) + RFP + ethambutol (EMB) + SM resistance in 500 m buffer were 0.276 (0.119–0.639) in NDVI model, 0.279 (0.11–0.705) in NDVI + PM10 model, 0.281 (0.111–0.713) in NDVI + PM2.5 model, 0.279 (0.11–0.709) in NDVI + SO2 model, 0.296 (0.117–0.754) in NDVI + NO2 model, 0.294 (0.116–0.748) in NDVI + O3 model, respectively. The study showed, for the first time, that residential greenness exposure in 500 m buffer is beneficial for reducing newly-diagnosed DR-TB (including PDR-RB, MDR-TB, MR-TB), and ambient air pollutants may partially mediate this association. [ABSTRACT FROM AUTHOR]

Wearable electronics with great breathability enable a comfortable wearing experience and facilitate continuous biosignal monitoring over extended periods1–3. However, current research on permeable electronics is predominantly at the stage of electrode and substrate development, which is far behind practical applications with comprehensive integration with diverse electronic components (for example, circuitry, electronics, encapsulation)4–8. Achieving permeability and multifunctionality in a singular, integrated wearable electronic system remains a formidable challenge. Here we present a general strategy for integrated moisture-permeable wearable electronics based on three-dimensional liquid diode (3D LD) configurations. By constructing spatially heterogeneous wettability, the 3D LD unidirectionally self-pumps the sweat from the skin to the outlet at a maximum flow rate of 11.6 ml cm−2 min−1, 4,000 times greater than the physiological sweat rate during exercise, presenting exceptional skin-friendliness, user comfort and stable signal-reading behaviour even under sweating conditions. A detachable design incorporating a replaceable vapour/sweat-discharging substrate enables the reuse of soft circuitry/electronics, increasing its sustainability and cost-effectiveness. We demonstrated this fundamental technology in both advanced skin-integrated electronics and textile-integrated electronics, highlighting its potential for scalable, user-friendly wearable devices.Incorporation of a ‘liquid diode’ into a wearable electronic platform enhances comfort and stability by shunting away sweat as it accumulates. [ABSTRACT FROM AUTHOR]

Transfusion reactions induced by platelet transfusions may be reduced and alleviated by leukocyte reduction of platelets. Although leukoreduction of apheresis platelets can be performed either pre-storage or post-storage, seldom studies directly compare the incidence of transfusion reaction in these two different blood products. We conducted a retrospective study to compare the transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets. We reviewed the general characteristics and the transfusion reactions, symptoms, and categories for inpatients who received pre-storage or post-storage leukoreduced apheresis platelets. Propensity-score matching was performed to adjust for baseline differences between groups. A total of 40,837 leukoreduction apheresis platelet orders were reviewed. 116 (0.53%) transfusion reactions were reported in 21,884 transfusions with pre-storage leukoreduction, and 174 (0.91%) reactions were reported in 18,953 transfusions with post-storage leukoreduction. Before propensity-score matching, the odds ratio for transfusion reactions in the pre-storage group relative to the post-storage group was 0.57 (95% confidence interval [CI] 0.45–0.72, P < 0.01); the odds ratio after matching was 0.63 (95% CI 0.49–0.80, P < 0.01). A two-proportion z-test revealed pre-storage leukoreduction significantly decreases the symptoms of chills, fever, itching, urticaria, dyspnea, and hypertension as compared with those in post-storage leukoreduction. Pre-storage leukoreduced apheresis platelet significantly decreased febrile non-hemolytic transfusion reaction as compared with post-storage groups. This study suggests pre-storage leukoreduction apheresis platelet significantly decreases the transfusion reaction as compared with those in post-storage leukoreduction. [ABSTRACT FROM AUTHOR]

Purpose: We described the clinical and densitometric characteristics and treatment outcomes of patients who developed atypical femoral fractures (AFF) while on bisphosphonate for osteoporosis. Methods: We performed a retrospective cohort study including all adults aged ≥50 years who developed AFF while on bisphosphonates between 1 January 2008 and 31 December 2020, and subsequently managed in the Osteoporosis Centre at Queen Mary Hospital in Hong Kong. A control group of patients who developed fragility hip fractures while on bisphosphonates in the same period was included for comparison. We compared the clinical and densitometric characteristics between the two groups, and described the clinical outcomes for the AFF group. Results: In total, 75 patients were included (AFF: n = 35; fragility hip fracture: n = 40). All were related to oral bisphosphonates. The AFF group was characterised by a longer duration of bisphosphonate use (median of 5 years), higher bone mineral density (BMD) and more acute neck-shaft angle (all p < 0.05). Following AFF, 8 patients (22.9%) did not receive any subsequent bone-active agents: due to refusal to use an injectable, or BMD out of osteoporotic range. Most of those who received bone-active agents were given teriparatide, followed by raloxifene, and achieved stable BMD. However, subsequent fragility risk remained high. Nonetheless, AFF did not confer excess morbidity and mortality. Conclusion: AFF was characterised by usually long duration of bisphosphonate use, higher BMD and more acute neck-shaft angle. AFF did not confer significant impairment in mobility or mortality. Nonetheless, further research work is necessary to optimise bone health among patients who develop AFF. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to determine the diagnostic criteria of myosteatosis in a Chinese population and investigate the effect of skeletal muscle abnormalities on the outcomes of cirrhotic patients. Methods: Totally 911 volunteers were recruited to determine the diagnostic criteria and impact factors of myosteatosis, and 480 cirrhotic patients were enrolled to verify the value of muscle alterations for prognosis prediction and establish new noninvasive prognostic strategies. Results: Multivariate analysis showed age, sex, weight, waist circumference, and biceps circumference had a remarkable influence on the L3 skeletal muscle density (L3-SMD). Based on the cut-off of a mean − 1.28 × SD among adults aged < 60 years, the diagnostic criteria for myosteatosis was L3-SMD < 38.93 Hu in males and L3-SMD < 32.82 Hu in females. Myosteatosis rather than sarcopenia has a close correlation with portal hypertension. The concurrence of sarcopenia and myosteatosis not only is associated with poor liver function but also evidently reduced the overall and liver transplantation-free survival of cirrhotic patients (p < 0.001). According to the stepwise Cox regression hazard model analysis, we established nomograms including TBil, albumin, history of HE, ascites grade, sarcopenia, and myosteatosis for easily determining survival probabilities in cirrhotic patients. The AUC is 0.874 (95% CI 0.800–0.949) for 6-month survival, 0.831 (95% CI 0.764–0.898) for 1-year survival, and 0.813 (95% CI 0.756–0.871) for 2-year survival prediction, respectively. Conclusions: This study provides evidence of the significant correlation between skeletal muscle alterations and poor outcomes of cirrhosis, and establishes valid and convenient nomograms incorporating musculoskeletal disorders for the prognostic prediction of liver cirrhosis. Further large-scale prospective studies are necessary to verify the value of the nomograms. [ABSTRACT FROM AUTHOR]

A series of 1-benzo[1,3]dioxol-5-yl-indoles bearing 3-N-fused heteroaryl moieties have been designed based on literature reports of the activity of indoles against various cancer cell lines, synthesized via a Pd-catalyzed C-N cross-coupling, and evaluated for their anticancer activity against prostate (LNCaP), pancreatic (MIA PaCa-2), and acute lymphoblastic leukemia (CCRF-CEM) cancer cell lines. A detailed structure–activity relationship study culminated in the identification of 3-N-benzo[1,2,5]oxadiazole 17 and 3-N-2-methylquinoline 20, whose IC50 values ranged from 328 to 644 nM against CCRF-CEM and MIA PaCa-2. Further mechanistic studies revealed that 20 caused cell cycle arrest at the S phase and induced apoptosis in CCRF-CEM cancer cells. These 1-benzo[1,3]dioxol-5-yl-3-N-fused heteroaryl indoles may serve as a template for further optimization to afford more active analogs and develop a comprehensive understanding of the structure–activity relationships of indole anticancer molecules. [ABSTRACT FROM AUTHOR]

Image super-resolution, a technique for image restoration, has been the subject of extensive research. The challenge lies in converting a low-resolution image to recover its high-resolution information, a problem that researchers have been persistently exploring. Early physical transformation methods often resulted in high-resolution images with significant information loss, and the edges and details were not well recovered.With advancements in hardware technology and mathematics, deep learning methods have been employed for image super-resolution tasks. These range from direct deep learning models, residual channel attention networks, bi-directional suppression networks, to networks with transformer modules, all of which have progressively yielded satisfactory results.In the realm of multi-image super-resolution, the establishment of a multi-image super-resolution dataset has facilitated the evolution from convolution models to transformer models, thereby continuously enhancing the quality of super-resolution. However, it has been observed that neither pure convolution nor pure transformer networks can effectively utilize low-resolution image information.To address this, we propose a novel end-to-end CoT-MISR network. The CoT-MISR network compensates for local and global information by leveraging the strengths of both convolution and transformer techniques. Validation on an equal parameter dataset demonstrates that our CoT-MISR network has achieved the optimal score index. [ABSTRACT FROM AUTHOR]

This study evaluated the effects of planning methods—pushing and pulling—on the surface topographic characteristics of Cedrela sinensis and Korean Paulownia wood boards according to ISO 25178 standards. Surface roughness was assessed using a stylus profilometer (Mitutoyo SJ301) and a 3D Optical Profilometer (VR-6000, Keyence). The parameters measured included arithmetical mean height (Ra and Sa), root mean square roughness (Rq), average maximum height of the surface (Rz and Sz), texture aspect ratio (Str), the spatial parameter of the surface (Spc), and developed interfacial area ratio (Sdr). These parameters collectively provide a comprehensive description of a surface's texture, aiding in assessing its roughness, directionality, and functional characteristics. On average, Cedrela sinensis push-finished surfaces showed Ra of 16.78 μm, while pull-finished surfaces showed Ra of 11.22 μm. For Paulownia, push-finished surfaces had Ra of 6.04 μm, while pull-finished surfaces had Ra of 5.83 μm. Statistical t-test results showed no significant differences between push and pull planning methods (p > 0.05). The surface roughness analysis reveals that Cedrela sinensis surfaces exhibit higher roughness, more significant height variations, and more complex textures than Paulownia. These findings are valuable for the woodworking industry, offering insights into optimizing planning methods for specific wood species and applications. [ABSTRACT FROM AUTHOR]

Efficient pretreatment of wheat straw (WS) under mild conditions facilitates its further enzymatic hydrolysis and conversion. Three pretreatment processes with mild conditions including formic acid pretreatment (FAP), sodium chlorite pretreatment (SCP), and alkaline hydrogen peroxide (AHP) pretreatment were investigated in this study. The chemical components of WS before and after pretreatment were compared, and the samples were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The lignin removal by FAP, SCP, and AHP pretreatment was 55.79%, 99.33%, and 94.97%, and the enzymatic hydrolysis yields (EHY) were 68.03%, 75.52%, and 90.76%, respectively. The results showed that AHP pretreatment had a better performance on enzyme accessibility thus improving the EHY. Meanwhile, lignin can be separated from the AHP pretreatment liquid, which helps to improve the economics of the process. The effects of enzymes and additives on enzymatic hydrolysis were further optimized by response surface methodology. Under the conditions of 20.37 FPU/g cellulase, 32.14 IU/g xylanases, and 19.15 mg/g Tween 80, the experimental result showed that the maximum EHY was 94.15%, which was close to the predicted EHY (96.19%). The experiments on fed-batch mode after AHP pretreatment with high-solid loadings (20% w/v) were conducted, and the EHY reached 86.05%. These results contributed to improving the economic feasibility of WS pretreatment and enzymatic hydrolysis process. [ABSTRACT FROM AUTHOR]