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Topological edge states are a generic feature of topological insulators, and the long-range interactions, which break certain properties of topological edge states, are always non-negligible in real physical systems. In this Letter, we investigate the influence of next-nearest-neighbor (NNN) interactions on the topological properties of the Su-Schrieffer-Heeger (SSH) model by extracting the survival probabilities at the boundary of the photonic lattices. By introducing a series of integrated photonic waveguide arrays with different strengths of long-range interactions, we experimentally observe delocalization transition of light in SSH lattices with nontrivial phase, which is in good agreement with our theoretical predictions. The results indicate that the NNN interactions can significantly affect the edge states, and that the localization of these states can be absent in topologically nontrivial phase. Our work provides an alternative way to investigate the interplay between long-range interactions and localized states, which may stimulate further interest in topological properties in relevant structures.

Our group have demonstrated that splenic B cells contributed to the CD4 + CD25 - naive T cells conversion into CD4 + CD25 + Foxp3 - regulatory T cells without adding appended cytokines, named Treg-of-B cells which were potent suppressors of adaptive immunity. We like to investigate whether Treg-of-B cells could promote alternatively activated macrophage (M2 macrophages) polarization and alleviate inflammatory disease, psoriasis. In this study, we co-cultured the bone marrow-derived macrophages (BMDMs) with Treg-of-B cells under LPS/IFN-γ stimulation and analyzed the M2-associated gene and protein using qPCR, western blotting, and immunofluorescence staining. We also examined the therapeutic effect of Treg-of-B cell-induced M2 macrophage for skin inflammation using imiquimod (IMQ)-induced psoriatic mouse model. Our results showed that BMDMs co-cultured with Treg-of-B cells upregulated typical M2-associated molecules, including Arg-1, IL-10, Pdcd1lg2, MGL-1, IL-4, YM1/2 and CD206. In an inflammatory environment, TNF-α and IL-6 production by macrophages co-cultured with Treg-of-B cells was decreased significantly. The molecular mechanism revealed that Treg-of-B cells promoted M2 macrophage polarization via STAT6 activation in a cell contact-dependent manner. Moreover, the treatment with Treg-of-B cell-induced M2 macrophages attenuated the clinical manifestations of psoriasis, such as scaling, erythema and thickening in the IMQ-induced psoriatic mouse model. T cell activation in draining lymph nodes was decreased in the Treg-of-B cell-induced M2 macrophage group after IMQ application. In conclusion, our findings suggested that Foxp3 - Treg-of-B cells could induce alternatively activated M2 macrophages through STAT6 activation, providing a cell-based therapeutic strategy for psoriasis., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: This study aimed at the evaluation and assessment of a simple method, the transverse process resection (TPR) technique, for freehand thoracic pedicle screw placement and the learning curve for trainee surgeons., Methods: In the TPR technique, the tip of the thoracic transverse process (TP) is removed to create an entry point in the cancellous bone of the TP, and the thoracic pedicle is cannulated from the TP. We retrospectively evaluated the safety and radiographic results of the TPR technique and compared with that of conventional pedicle screws. The training performance of seven neurosurgical residents with TPR techniques were evaluated., Results: Among 46 patients, a total of 322 thoracic screws were analyzed, including 178 screws placed using the TPR technique and 144 screws using the conventional straight-forward (SF) technique. TPR screws had greater medial angulations in all levels from T2 to T12 compared to SF screws ( p  < 0.001). The incidence of pedicle breach was lower in the TPR screws compared to SF screws (6.2% vs. 21.5%, p < 0.001), especially for screws placed by residents (6.7% vs. 29.6%, p  < 0.001). Residents had improved performance following a cadaveric training course on the TPR technique ( p  = 0.001)., Conclusion: This study demonstrated the safety of the TPR technique for thoracic pedicle screw placement and its short learning curve for trainee surgeons.

TAR DNA-binding protein-43 (TDP-43) proteinopathies are accompanied by the pathological hallmark of cytoplasmic inclusions in the neurodegenerative diseases, including frontal temporal lobar degeneration-TDP and amyotrophic lateral sclerosis. We found that transthyretin accumulates with TDP-43 cytoplasmic inclusions in frontal temporal lobar degeneration-TDP human patients and transgenic mice, in which transthyretin exhibits dramatic expression decline in elderly mice. The upregulation of transthyretin expression was demonstrated to facilitate the clearance of cytoplasmic TDP-43 inclusions through autophagy, in which transthyretin induces autophagy upregulation via ATF4. Of interest, transthyretin upregulated ATF4 expression and promoted ATF4 nuclear import, presenting physical interaction. Neuronal expression of transthyretin in frontal temporal lobar degeneration-TDP mice restored autophagy function and facilitated early soluble TDP-43 aggregates for autophagosome targeting, ameliorating neuropathology and behavioural deficits. Thus, transthyretin conducted two-way regulations by either inducing autophagy activation or escorting TDP-43 aggregates targeted autophagosomes, suggesting that transthyretin is a potential modulator therapy for neurological disorders caused by TDP-43 proteinopathy., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Enhanced recovery after surgery (ERAS) measures have not been systematically applied in transurethral surgery for benign prostatic hyperplasia (BPH). This study was performed on patients with BPH who required surgical intervention. From July 2019 to June 2020, the ERAS program was applied to 248 patients, and the conventional program was applied to 238 patients. After 1 year of follow-up, the differences between the ERAS group and the conventional group were evaluated. The ERAS group had a shorter time of urinary catheterization compared with the conventional group (mean ± standard deviation [s.d.]: 1.0 ± 0.4 days vs 2.7 ± 0.8 days, P < 0.01), and the pain (mean ± s.d.) was significantly reduced through postoperative hospitalization days (PODs) 0-2 (POD 0: 1.7 ± 0.8 vs 2.4 ± 1.0, P < 0.01; POD 1: 1.6 ± 0.9 vs 3.5 ± 1.3, P < 0.01; POD 2: 1.2 ± 0.7 vs 3.0 ± 1.3, P < 0.01). No statistically significant difference was found in the rate of postoperative complications, such as postoperative bleeding (P = 0.79), urinary retention (P = 0.40), fever (P = 0.55), and readmission (P = 0.71). The hospitalization cost of the ERAS group was similar to that of the conventional group (mean ± s.d.: 16 927.8 ± 5808.1 Chinese Yuan [CNY] vs 17 044.1 ± 5830.7 CNY, P =0.85). The International Prostate Symptom Scores (IPSS) and quality of life (QoL) scores in the two groups were also similar when compared at 1 month, 3 months, 6 months, and 12 months after discharge. The ERAS program we conducted was safe, repeatable, and efficient. In conclusion, patients undergoing the ERAS program experienced less postoperative stress than those undergoing the conventional program., Competing Interests: None

Sexually exploited adolescent girls are disproportionately affected by adverse psychosocial conditions, such as intra-familial child physical and sexual abuse, extra-familial violence and sexual assault, alcohol and drug use, and suicide. Syndemic theory suggests that these adverse psychosocial or syndemic conditions are concentrated and co-occurring in socially marginalized populations, including sexually exploited adolescents, and increase their sexual health risks, including pregnancy, abortion, and the acquisition of sexually transmitted diseases (STDs). To examine clusters of syndemic conditions, latent class analysis (LCA) was conducted to classify 335 sexually exploited girls in Taiwan into subgroups based on their probability of experiencing each syndemic condition. We used syndemic class membership to predict their sexual health outcomes, specifically pregnancy, abortion, and the acquisition of STDs. The results of LCA revealed three classes, which were "low-risk syndemic," "moderate-risk syndemic," and "high-risk syndemic." The risk of acquisition of STDs among sexually exploited girls in the "high-risk syndemic class" and "moderate-risk syndemic class" was 239% and 135% higher, respectively, than the risk of acquisition of STDs among sexually exploited girls in the "low-risk syndemic class." Differences between these three classes in pregnancy and abortion were not significant. Our findings support the syndemic theory that a pattern of syndemic conditions is associated with an increased risk of acquiring STDs. Interventions aimed at reducing the acquisition of STDs among sexually exploited girls in Taiwan should adopt a comprehensive approach to address co-occurring conditions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

PBRM1 encodes an accessory subunit of the PBAF SWI/SNF chromatin remodeller, and the inactivation of PBRM1 is a frequent event in kidney cancer. However, the impact of PBRM1 loss on chromatin remodelling is not well examined. Here we show that, in VHL-deficient renal tumours, PBRM1 deficiency results in ectopic PBAF complexes that localize to de novo genomic loci, activating the pro-tumourigenic NF-κB pathway. PBRM1-deficient PBAF complexes retain the association between SMARCA4 and ARID2, but have loosely tethered BRD7. The PBAF complexes redistribute from promoter proximal regions to distal enhancers containing NF-κB motifs, heightening NF-κB activity in PBRM1-deficient models and clinical samples. The ATPase function of SMARCA4 maintains chromatin occupancy of pre-existing and newly acquired RELA specific to PBRM1 loss, activating downstream target gene expression. Proteasome inhibitor bortezomib abrogates RELA occupancy, suppresses NF-κB activation and delays growth of PBRM1-deficient tumours. In conclusion, PBRM1 safeguards the chromatin by repressing aberrant liberation of pro-tumourigenic NF-κB target genes by residual PBRM1-deficient PBAF complexes., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Childhood asthma is a heterogeneous disease characterized by chronic airway inflammation, leading to a broad range of clinical presentations. Nonallergic asthma is asthma without allergic sensitization. Both clinical manifestations and immunopathological mechanisms of nonallergic childhood asthma were rarely investigated. We aimed to compare the clinical features between nonallergic and allergic childhood asthma and apply microRNA to explore the underlying mechanism of nonallergic childhood asthma. We enrolled 405 asthmatic children (76 nonallergic, 52 allergic with total IgE < 150 IU/mL and 277 allergic with total IgE > 150 IU/mL). Clinical characteristics were compared between groups. Comprehensive miRNA sequencing (RNA-seq) was performed using peripheral blood from 11 nonallergic and 11 allergic patients with elevated IgE, respectively. Differentially expressed miRNA (DEmiRNA) were determined with DESeq2. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis was performed to determine functional pathways involved. Publicly available mRNA expression data was applied to investigate the predicted target mRNA networks via Ingenuity Pathway Analysis (IPA). The average age of nonallergic asthma was significantly younger (5.614 ± 2.743 vs 6.676 ± 3.118 years-old). Higher severity and worse control were more common in nonallergic asthma (two-way ANOVA, P < 0.0001). Long-term severity was higher, and intermittent attacks persisted in nonallergic patients. We identified 140 top DEmiRNAs based on false discovery rate (FDR) q-value < 0.001. Forty predicted target mRNA gene were associated with nonallergic asthma. The enriched pathway based on GO included Wnt signaling pathway. IgE expression was predicted to be downregulated by a network involving simultaneous interaction with IL-4, activation of IL-10 and inhibition of FCER2. Nonallergic childhood asthma were distinct in their younger age, higher long-term severity and more persistent course. Differentially expressed miRNA signatures associate with downregulation of total IgE expression and predicted target mRNA genes related molecular networks contribute to canonical pathways of nonallergic childhood asthma. We demonstrated the negative role of miRNAs involved in regulating IgE expression indicating differences between asthma phenotypes. Identification of biomarkers of miRNAs could contribute to understand the molecular mechanism of endotypes in nonallergic childhood asthma, which can potentially allow delivery of precision medicine to pediatric asthma., (© 2023. The Author(s).)

The tremendous public health and economic impact of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a huge challenge globally. There is increasing evidence that SARS-CoV-2 induces intestinal infections. Type III interferon (IFN-λ) has an antiviral role in intestinal infection, with focused, long-lasting, and non-inflammatory characteristics. This review presents a summary of the structure of SARS-CoV-2, including its invasion and immune escape mechanisms. Emphasis was placed on the gastrointestinal impact of SARS-CoV-2, including changes to the intestinal microbiome, activation of immune cells, and inflammatory responses. We also describe the comprehensive functions of IFN-λ in anti-enteric SARS-CoV-2 infection, and discuss the potential application of IFN-λ as a therapeutic agent for COVID-19 with intestinal symptoms., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

A dimethylaniline (donor)-indanedione (acceptor) conjugate (sensor 1) with a very low molecular weight of 277 g mol -1 and intramolecular charge transfer (ICT) characteristics was synthesized. Sensor 1 shows weak ICT fluorescence in solution, but strong emission (Φ=16%) in the solid state owing to intramolecular and intermolecular C-H⋅⋅⋅O hydrogen bonds that inhibit the free rotation of the exocyclic C-C single bond. Compared to yellow emitter 1Y, which has a similar donor-acceptor structure, sensor 1 shows red fluorescence in the solid state owing to J-aggregate formation. The colorimetric and fluorometric responses of sensor 1 to cyanide in both solution and solid state are due to the nucleophilic addition of cyanide to the β-conjugated carbon of the indanedione group, which prohibits ICT. Additionally, inexpensive portable paper-based test kits based on sensor 1 were easily prepared and could be used for fast and quantitative naked-eye cyanide detection in real time., (© 2023 Wiley-VCH GmbH.)

Background: The oral glucose tolerance test is a common method of diagnosing gestational diabetes mellitus. This test causes several unpleasant side effects such as nausea, vomiting, abdominal bloating, and headache., Objective: This study aimed to assess the effect of liquid temperature and additives on pregnant women's taste perception, side effects, and glycemic levels in an oral glucose tolerance test., Study Design: This study was a single-center, randomized, and multi- and open-arm clinical trial. A total of 399 participants receiving the 75-g oral glucose tolerance test for gestational diabetes mellitus diagnosis were included. Solutions for use in the 75-g oral glucose tolerance test were prepared in 8 formulas, with the participants randomly assigned to 1 of the 8 groups: room-temperature water, hot water, cold water, hot water with tea bag, room-temperature water with tea bag, cold water with tea bag, room-temperature soda water, and cold soda water. The main study outcomes were glycemic levels, satisfaction, perceived taste, side effects, and gestational diabetes mellitus. Glycemic levels were measured when fasted and at 1 hour and 2 hours after glucose administration. Satisfaction, taste perception, and side effects were evaluated immediately after the oral glucose tolerance test, and gestational diabetes mellitus was determined on the basis of glycemic levels., Results: The cold soda water solution led to a significantly higher glycemic level at 1 hour after glucose intake compared with room-temperature soda water solution (P=.009). Glucose formula was found to not significantly affect gestational diabetes mellitus incidence (P>.05) or the participants' satisfaction, vomiting, headache, or abdominal bloating (P>.05). However, the formula did significantly affect perceived taste (P=.027) and the degree of nausea (P=.014)., Conclusion: Several glucose solutions, such as cold glucose solution and any-temperature glucose solution containing a tea bag, led to slightly higher taste scores and a lower degree of nausea compared with the room-temperature water-based glucose solution. However, soda water was found to affect the glycemic level at 1 hour after glucose intake, and is not suggested for use for gestational diabetes mellitus diagnosis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Human activities impose significant changes on sedimentation processes and vegetation cover within lake catchments. However, the needed time for an anthropogenically disturbed natural state to be reversed back to its natural state by environmental protection programs is still ambiguous. Here we employ a multi-proxy approach to delineate major environmental disturbances such as logging and forest fires on the catchment in Cueifong Lake, a subtropical subalpine lake in northeastern Taiwan. X-ray Fluorescence (XRF) core scanning, bulk total organic carbon (TOC), bulk total nitrogen (TN), stable carbon isotope (δ 13 C org ) analysis, and macro-charcoal counting were utilized to reconstruct changes in the catchment environment based on a sediment core from Cueifong Lake. The results show that the element content changed distinctly around 1975 CE, which coincided with the onset of profound deforestation in the lake vicinity recorded in historical documents and aerial photos. After the cessation of the logging event, the detrital input increased, accompanied by decreasing C/N ratios and increasing δ 13 C org values. This suggests that increased terrestrial nutrient input promoted algae growth. After the deforestation phase, our results imply a gradual recovery of elemental composition in the catchment environment. By extrapolating the XRF element records, we suggest that it might take >50 years for the sedimentary regime to reach its pre-logging baseline. In contrast to the depositional system, the C/N and δ 13 C org shifted significantly - potentially irreversibly - towards an algae-dominant environment instead of recovering to the pre-logging condition. This could be due to both 1) the changes in the different vegetation species used for reforestation and/or 2) anthropogenically introduced fishes in the 1980s. This study proposes the first assessment of the needed recovery time for subtropical Asian subalpine forests after large-scale logging activity and thus provides an apparent reference for policy decisions on natural resource development and environmental protection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Lupus nephritis (LN) is a crucial organ involvement in systemic lupus erythematosus (SLE). Patients with LN have higher morbidity and mortality rates than those without. Among all patients with LN, 20-40% had delayed onset, but the data for patients with juvenile-onset SLE (jSLE), who have a higher percentage of LN than patients with adult-onset SLE (aSLE), were limited. This study aimed to determine the risk factors for subsequent LN in patients with jSLE., Methods: A retrospective cohort study was conducted between 2008 and 2018 in a single tertiary medical centre. Patients with diagnosed jSLE were reviewed. We investigated those without LN at diagnosis and whether they developed LN afterward. The primary outcome was the development of subsequent LN. Clinical manifestations at diagnosis, serial laboratory data, and treatments were reviewed during follow-up periods., Results: Among the 48 patients with jSLE without initial LN, 20 developed subsequent LN later (Group 1), whereas 28 remained free of LN (Group 2). There was no difference in the percentage of initial manifestations except for more discoid rashes in Group 2 patients. In the Cox regression model, elevated average anti-double-stranded DNA (dsDNA) antibody, low average serum complements, and high average erythrocyte sedimentation rate (ESR) levels during follow-up were predictors of subsequent LN. After adjusting for these factors in multivariable analyses, only high average anti-dsDNA antibody and high average ESR levels remained predictive of subsequent LN. For every 100 IU/ml increase in anti-dsDNA antibody, the risk for subsequent LN in jSLE increases by 1.29 times (hazard ratio = 1.29, 95% confidence interval 1.055-1.573)., Conclusion: Persistently high anti-dsDNA antibody and ESR levels during the follow-up period were risk factors for subsequent LN in patients with jSLE., (© 2023. The Author(s).)

Carbenes are highly active reaction intermediates, which can be used as reaction precursors to modify organisms, drugs, and material molecules. In this work, we realized a new cheap metal-catalyzed carbonylation of carbene to give propanedioic acid derivatives. With copper salt as the catalyst, synthetically important malonates and related compounds were produced in good yields under mild reaction conditions.

Background: Calcific aortic stenosis (CAS) is the most common valvular heart disease in older adults and has no effective preventive therapies. Genome-wide association studies (GWAS) can identify genes influencing disease and may help prioritize therapeutic targets for CAS., Methods: We performed a GWAS and gene association study of 14 451 patients with CAS and 398 544 controls in the Million Veteran Program. Replication was performed in the Million Veteran Program, Penn Medicine Biobank, Mass General Brigham Biobank, BioVU, and BioMe, totaling 12 889 cases and 348 094 controls. Causal genes were prioritized from genome-wide significant variants using polygenic priority score gene localization, expression quantitative trait locus colocalization, and nearest gene methods. CAS genetic architecture was compared with that of atherosclerotic cardiovascular disease. Causal inference for cardiometabolic biomarkers in CAS was performed using Mendelian randomization and genome-wide significant loci were characterized further through phenome-wide association study., Results: We identified 23 genome-wide significant lead variants in our GWAS representing 17 unique genomic regions. Of the 23 lead variants, 14 were significant in replication, representing 11 unique genomic regions. Five replicated genomic regions were previously known risk loci for CAS ( PALMD, TEX41, IL6, LPA, FADS ) and 6 were novel ( CEP85L, FTO, SLMAP, CELSR2, MECOM, CDAN1 ). Two novel lead variants were associated in non-White individuals ( P <0.05): rs12740374 ( CELSR2 ) in Black and Hispanic individuals and rs1522387 ( SLMAP ) in Black individuals. Of the 14 replicated lead variants, only 2 (rs10455872 [ LPA ], rs12740374 [ CELSR2 ]) were also significant in atherosclerotic cardiovascular disease GWAS. In Mendelian randomization, lipoprotein(a) and low-density lipoprotein cholesterol were both associated with CAS, but the association between low-density lipoprotein cholesterol and CAS was attenuated when adjusting for lipoprotein(a). Phenome-wide association study highlighted varying degrees of pleiotropy, including between CAS and obesity at the FTO locus. However, the FTO locus remained associated with CAS after adjusting for body mass index and maintained a significant independent effect on CAS in mediation analysis., Conclusions: We performed a multiancestry GWAS in CAS and identified 6 novel genomic regions in the disease. Secondary analyses highlighted the roles of lipid metabolism, inflammation, cellular senescence, and adiposity in the pathobiology of CAS and clarified the shared and differential genetic architectures of CAS with atherosclerotic cardiovascular diseases.

Dengue virus (DENV) infection can induce life-threatening dengue hemorrhagic fever/dengue shock syndrome in infected patients. DENV is a threat to global health due to its growing numbers and incidence of infection in the last 50 years. During infection, DENV expresses ten structural and nonstructural proteins modulating cell responses to benefit viral replication. However, the lack of knowledge regarding the cellular proteins and their functions in enhancing DENV pathogenesis impedes the development of antiviral drugs and therapies against fatal DENV infection. Here, we identified that integrin-linked kinase (ILK) is a novel enhancing factor for DENV infection by suppressing type I interferon (IFN) responses. Mechanistically, ILK binds DENV NS1 and NS3, activates Akt and Erk, and induces NF-κB-driven suppressor of cytokine signaling 3 (SOCS3) expression. Elevated SOCS3 in DENV-infected cells inhibits phosphorylation of STAT1/2 and expression of interferon-stimulated genes (ISGs). Inhibiting ILK, Akt, or Erk activation abrogates SOCS3 expression. In DENV-infected mice, the treatment of an ILK inhibitor significantly reduces viral loads in the brains, disease severity, and mortality rate. Collectively, our results show that ILK is a potential therapeutic target against DENV infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Neisseria gonorrhoeae (GC) is a obligate human pathogen responsible for gonorrhea, one of the most common sexually transmitted infections. The yearly increased multidrug resistance in GC has led to treatment failure clinically, suggesting an urgent need for novel therapy to combat this global health issue. AS101 [ammonium trichloro(dioxoethylene-O,O'-)tellurate], a tellurium-based compound previously used as an immunomodulatory agent, was found to have antimicrobial effects against Klebsiella pneumoniae via a high-throughput drug screening and showed antibacterial activity against Acinetobacter spp. This study aimed to evaluate the in vitro anti-gonococcal activity of AS101, including its antimicrobial activity, biofilm and infectivity inhibition, and potential underlying mechanisms. The agar-dilution-based MIC was used. The inhibition of GC microcolony formation and continual growth by AS101 was assessed by microscopy. The effect of AS101 on GC infectivity was evaluated by infecting endocervical ME180 and colorectal T84 epithelial cell lines. The mode of action was evaluated by a time-killing curve, transmission electron microscopy (TEM), and the level of reactive oxygen species (ROS). The MICs of MS11 and WHO GC isolates were both found to be 0.05 μg/mL. The biofilm formation, continual growth, and infectivity of two epithelial cell lines were significantly decreased with AS101 treatment. The time-kill curve, similar to that of azithromycin, suggested that AS101 is a bacteriostatic antimicrobial. However, TEM and ROS levels implied a mode of action different from that of azithromycin. Our findings highlighted the robust anti-gonococcal activities of AS101, which potentiates its use as a future antimicrobial for GC. IMPORTANCE Neisseria gonorrhoeae is an obligate human pathogen responsible for gonorrhea, one of the most common sexually transmitted infections. The yearly increased multidrug resistance in GC has led to treatment failure clinically, suggesting an urgent need for novel therapy to combat the global health issue. This study aimed to evaluate the in vitro anti-gonococcal activity of a previous immunomodulatory agent, AS101, and its underlying mechanisms. Here, we report that AS101 possesses remarkable anti-gonococcal activity. These findings supported further studies on in vivo experiments and formulations for the clinical application of AS101 as an anti-gonococcal agent.

The distinction between different separate primary lung cancers (SPLCs) and intrapulmonary metastases (IPMs) is a challenging but clinically significant issue. Histopathology-based classification is the current practice; however, it is subjective and affected by interobserver variability. Recently, next-generation sequencing (NGS) panels have been used in lung cancer diagnostics. This study aimed to investigate the value of large-scale NGS panels for distinguishing between SPLCs and IPMs. A total of 32 patients with 69 lung adenocarcinomas were included. Comprehensive histopathologic assessments of multiple pulmonary adenocarcinomas were performed independently by 3 pathologists. The consensus of histopathologic classification was determined by a majority vote. Genomic analysis was performed using an amplicon-based large-scale NGS panel, targeting single-nucleotide variants and short insertions and deletions in 409 genes. Tumor pairs were classified as SPLCs or IPMs according to a predefined molecular classification algorithm. Using NGS and our molecular classification algorithm, 97.6% of the tumor pairs can be unambiguously classified as SPLCs or IPMs. The molecular classification was predictive of postoperative clinical outcomes in terms of overall survival (P = .015) and recurrence-free interval (P = .0012). There was a moderate interobserver agreement regarding histopathologic classification (κ = 0.524 at the tumor pair level). The concordance between histopathologic and molecular classification was 100% in cases where pathologists reached a complete agreement but only 53.3% where they did not. This study showed that large-scale NGS panels are a powerful modality that can help distinguish SPLCs from IPMs in patients with multiple lung adenocarcinomas and objectively provide accurate risk stratification., (Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

The concentrations level and distribution of 16 US EPA polycyclic aromatic hydrocarbon (PAHs) from the water treatment plant (WTP), sewage treatment plant (STP), and industrial water treatment plant (ITP) sludge in Taiwan were determined and then assessed the sources, and potential toxicity (carcinogenic polycyclic aromatic hydrocarbons [CPAHs] and toxic BaP equivalent [TEQ]). Results indicated that the total concentrations of PAHs ranged between 58 and 16,436 μg/kg dw. Among the 17 samples, the 2-4 ring of total PAHs were the predominant compound in three kinds of treatment plant (> 60%). Especially, ITP1 owns 95.8% of 2-4 ring of total PAHs and ITP3 owns 54% of five- and six-ring of total PAHs. The molecular indices and principal component analysis (PCA) were used to determine the source contributions, with the results showing that the contributions of combustion/grass, coal or wood combustion and combustion/ liquid (oil) fossil fuel combustion. A PAH toxicity indicated by TEQ was 2.5-506 μg TEQ/g dw. Although, the results indicated that these were not recommended for land applications, but analyses are beneficial to develop effective management strategies for controlling PAH discharge in treatment plants and establishing strategies for its reuse in managing pollutants.

Tight junctions (TJs) are located in the apical region of the junctions between epithelial cells and are widely found in organs such as the brain, retina, intestinal epithelium, and endothelial system. As a mechanical barrier of the intestinal mucosa, TJs can not only maintain the integrity of intestinal epithelial cells but also maintain intestinal mucosal permeability by regulating the entry of ions and molecules into paracellular channels. Therefore, the formation disorder or integrity destruction of TJs can induce damage to the intestinal epithelial barrier, ultimately leading to the occurrence of various gastrointestinal diseases, such as inflammatory bowel disease (IBD), gastroesophageal reflux disease (GERD), and irritable bowel syndrome (IBS). However, a large number of studies have shown that TJs protein transport disorder from the endoplasmic reticulum to the apical membrane can lead to TJs formation disorder, in addition to disruption of TJs integrity caused by external pathological factors and reduction of TJs protein synthesis. In this review, we focus on the structural composition of TJs, the formation of clathrin-coated vesicles containing transmembrane TJs from the Golgi apparatus, and the transport process from the Golgi apparatus to the plasma membrane via microtubules and finally fusion with the plasma membrane. At present, the mechanism of the intracellular transport of TJ proteins remains unclear. More studies are needed in the future to focus on the sorting of TJs protein vesicles, regulation of transport processes, and recycling of TJ proteins, etc., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Previous research has suggested that psychological distress (i.e., anxiety, depression, and somatization) is associated with student victimization by teachers. The direction and causality of this relationship have not yet been empirically supported. This study examined longitudinal associations between adolescent psychological distress (anxiety, depression, and somatization) and student victimization by teachers among 419 adolescents in grades 7-9 of secondary schools in Hong Kong. A self-administered questionnaire was conducted to collect student self-reported information about their experiences of victimization by teachers and their psychological distress, including depression, anxiety, and somatization, at two time points separated by a 9-month interval. A cross-lagged panel analysis provided evidence for the contribution of depression, anxiety, and somatization to later victimization by teachers. These findings were also relevant for male and female adolescents. The findings suggest that psychological distress, such as depression, anxiety, and somatization, is a risk factor predicting student victimization by teachers rather than the consequences of exposure to teacher violence. The results support the importance of reducing adolescent depression, anxiety, and somatization symptoms in future intervention programs to prevent them from being victimized by teachers.

Optical waveguides prepared by femtosecond laser direct writing have birefringent properties, which can affect polarization encoding and entanglement on chips. Here, we first propose a shape-stress dual compensation fabrication scheme to decrease birefringence. Ultralow birefringent waveguides (1 × 10 -9 ) were obtained by controlling the cross sectional shape of the main waveguide and adjusting the position of the auxiliary lines. In addition, we prepared polarization-independent directional coupler and demonstrated the evolution of polarization-independent waveguide array with different polarized light. In the future, ultralow birefringent waveguides will be widely applied in polarization encoding and entangled quantum photonic integrated circuits.

Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease characterized by defective neutrophil killing of microbial pathogens and recurrent infections. We aimed to investigate the clinical, genetic features, treatment, and outcomes in patients with CGD., Methods: Pediatric patients diagnosed with CGD from a medical center in Taiwan were enrolled from January 1999 to Oct 2021., Results: Nine pediatric patients with CGD were enrolled: six X-linked (XL) CGD with CYBB gene mutations, three autosomal recessive (AR) CGD with two NCF1 and one CYBA gene mutations. The median age of onset and age of diagnosis was 0.92 and 2.64 years, respectively. Patients with XL-CGD had a younger age of onset (4.6 months vs. 1.83 years, P = 0.06) and age of diagnosis (1.71 vs. 8.86 years, P = 0.024) than AR-CGD patients. The most common sites of infections were skin and soft tissue abscesses. The most common pathogens were Staphylococcus, Serratia, and Salmonella spp. Prophylactic antibiotics, anti-fungal agents, and interferon-gamma (IFN-γ) were given in 9 (100%), 7 (77.8%), and 8 (88.9%) patients, respectively. The mean duration of IFN-γ usage was 5.15 years. One male patient with XL-CGD was successfully treated with hematopoietic stem cell transplantation at 2.2 years. The mortality rate was 11.1%, and the estimated overall survival at 20 years was 66.7%., Conclusion: Staphylococcus aureus, Serratia marcescens, and Salmonella infections are important in Taiwanese CGD patients. Patients with XL-CGD have early disease onset. IFN-γ prophylaxis and prophylactic anti-microbial agents might have an effect on alleviating the infection episodes in CGD patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

We introduce a novel tissue submission procedure without additional equipment or storage facilities for assessing the histological and immunohistochemical features of retinal tissues. In total, 150 specimens were collected from patients who underwent vitrectomy or macular surgery from January to December 2020. Ninety-eight specimens were submitted using the new procedure, and 58 specimens were submitted as flat-mount slides to compare specimen adequacy. The tissues submitted using the new procedure were subjected to paraffin-embedding and sectioning for hematoxylin & eosin staining. Additional immunohistochemical analysis was performed to assess the cellular composition in retinal tissues with diverse etiologies. The new submission procedure had an adequacy ratio of 75.51%, which was comparable to that of the flat-mount method (p = 0.1397). The new method could produce high-quality images of histological features of tissues and facilitated immunohistochemical analysis to demonstrate cell origins. More glial cells (p = 0.000) and myofibroblasts (p = 0.012) were detected in the epiretinal membranes (ERMs) than in the internal limiting membranes (ILMs). Subgroup analysis revealed that secondary ERMs contained more macrophage-like cells (p = 0.001) and retinal pigment epithelial cells (p = 0.000) than did idiopathic ERMs. Our novel tissue submission procedure can be applied to routine clinical practice. Our study provides additional histological and immunohistochemical evidence of cellular components in retinal tissues based on a large number of human tissue samples. Moreover, tissues submitted using the new method can be permanently preserved, enabling future investigation for potential prognostic or therapeutic targets., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: The cervicovaginal microbiota is essential for maintaining the health of the female reproductive tract. However, whether cervicovaginal microbiota status prior to frozen embryo transfer (FET) associates with pregnancy outcomes is largely unexplored., Methods: Cervical mucus from 29 women who had undergone FET was collected. Microbial composition was analyzed using 16 S rRNA gene sequence to assess the correlation to the pregnancy outcomes., Results: CST-categorized Lactobacillus was the most dominant (41.71%) in the pregnant group, while CST-IV-based and BV-related Gardnerella (34.96%) prevailed in the non-pregnant group. The average abundance of Gardnerella compared non-pregnant to pregnant women was the highest (34.96% vs. 4.22%, p  = 0.0015) among other CST-IV indicator bacteria. Multivariate analysis revealed that CST-IV-related bacteria have a significantly adverse effect on ongoing pregnancy outcomes (odds ratio, 0.083; 95% confidence index, 0.012-0.589, p  = 0.013*)., Conclusions: The study found that the CST-IV microbiota, with significantly increasing Gardnerella and the loss of Lactobacilli as the dominant bacteria, can potentially contribute to pregnancy failure. Therefore, dysbiotic microbiota may be a risk factor in women undergoing FET. Assessing the health of the cervicovaginal microbiota prior to FET would enable couples to make a more thoughtful decision on the timing and might improve pregnancy outcomes., Competing Interests: The authors declare no conflicts of interest related to the subject matter or materials discussed in this article., (© 2023 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Culture and personality are two central topics in psychology. Individuals are culturally influenced influencers of culture, yet the research linking culture and personality has been limited and fragmentary. We integrate the literatures on culture and personality with recent advances in socioecology and genetics to formulate the Socioecological-Genetic Framework of Culture and Personality. Our framework not only delineates the mutual constitution of culture and personality but also sheds light on ( a ) the roots of culture and personality, ( b ) how socioecological changes partly explain temporal trends in culture and personality, and ( c ) how genes and culture/socioecology interact to influence personality (i.e., nature × nurture interactions). By spotlighting the roles of socioecology and genetics, our integrative framework advances the understanding of culture and personality.

Lake Luoma is an important storage lake for the Eastern route of the South-to-North Water Diversion Project (NSBD), which has many functions including flood control and irrigation, drinking water supply, and ecological maintenance. In order to understand the succession patterns and driving factors of water quality in Lake Luoma, we used monthly monitoring data from 2009 to 2020 in combination with historical data from 1996 to 2008. The long-term succession patterns, seasonal dynamics, and spatial patterns of total nitrogen (TN), total phosphorus (TP), permanganate index, and ammonia nitrogen (NH + 4 -N) were examined, and the influence of meteorological and hydrological factors on water quality was explored through correlation analyses and generalized additive models. The results showed that it remained in the status of grade Ⅳ-inferior Ⅴ over the past 25 years. The concentration of TN, which was the main pollutant, changed significantly (1.06-3.49 mg·L -1 ), experiencing three stages of gradual decline (1996-2002), significant interannual fluctuation (2002-2015), and significant increase (2015-2020). Permanganate index decreased significantly (2.97-6.38 mg·L -1 ), whereas TP and NH + 4 -N concentration fluctuated slightly, ranging from 0.024-0.076 mg·L -1 and 0.11-0.69 mg·L -1 , respectively. The concentration of TN and TP increased abnormally in the summer of 2017-2020, reaching 3.30 mg·L -1 and 0.14 mg·L -1 in August, respectively, which was approximately 1.5 and 2.4 times the annual average. In terms of seasonal dynamics, the seasonal variation in water quality between summer/autumn and winter/spring reversed after 2015, with water quality in summer/autumn being worse than that in winter and spring, indicating the exacerbation of eutrophication. The water quality in the southern area was obviously better than that in the northern area. The input of pollutants from the Yihe River and Middle Canal increased with water quantity since 2015, which drove the water quality deterioration through nutrients. Our results suggested that the water quality of Lake Luoma should be improved by strengthening exogenous pollution reduction, endogenous control, polder dismantling, and ecological restoration.

BACKGROUND. Digital breast tomosynthesis (DBT) has led to increased detection of architectural distortion (AD). Management of patients with multiple areas of AD is not established. OBJECTIVE. The purpose of this article is to compare pathologic outcomes between single and multiple areas of AD identified on DBT. METHODS. This retrospective study included 402 patients (mean age, 56 years) who underwent image-guided core needle biopsy of AD visualized on DBT between April 7, 2017, and April 16, 2019. Patients were classified as having a single or multiple areas of AD according to the presence of distinct areas of AD described in the clinical radiology reports. The pathologic diagnosis for each AD was on the basis of the most aggressive pathology identified on either biopsy or surgical excision, if performed. Patients with single and multiple areas of AD were compared. RESULTS. The sample included 372 patients with a single AD (145 benign, 121 high risk, 105 malignant, one other) and 30 patients with multiple visualized ADs, including 66 biopsied ADs (10 benign, 35 high risk, 21 malignant). At pathologic assessment on a per-lesion basis, multiple compared with single ADs showed higher frequency of high-risk pathology (53.0% vs 32.5%, p = .002) but no difference in frequency of malignancy (31.8% vs 28.2%, p = .56). In multivariable analysis of a range of patient-related characteristics, the presence of single versus multiple areas of AD was not independently associated with malignancy ( p = .51). In patients with multiple areas of AD, the most aggressive pathology (benign, high risk, or malignant) across all ADs was not associated with the number of ADs ( p = .73). In 8 of 24 patients with at least two ipsilateral biopsied ADs, the ipsilateral areas varied in terms of most aggressive pathology; in 5 of 10 patients with contralateral biopsied ADs, the contralateral areas varied in most aggressive pathology. CONCLUSION. The presence of multiple areas of AD, compared with a single AD, was significantly more likely to yield high-risk pathology but was not significantly different in yield of malignancy. In patients with multiple ADs, multiple ipsilateral or contralateral ADs commonly varied in pathologic classification (benign, high risk, or malignant). CLINICAL IMPACT. These findings may help guide management of AD visualized by DBT, including multiple ADs. For patients with multiple areas of AD, biopsy of all areas may be warranted given variation in pathologic diagnoses.

The motorcycles are unignorable near-ground pollutant emission sources that increase the human exposure in the dense area. However, the information of the polycyclic aromatic hydrocarbons (PAHs) emissions under different scenarios of engine and emission control for motorcycle is limited. This study focused on the PAH emissions from two fuel-injection types of motorcycles, including the premixed fuel-injection (PFi) with carburetor and electronic fuel-injection (EFi). Specifically, the effects of throttle opening (TO), secondary air system (SAS), oxygen sensor (OS), oxidation catalytic converter (OCC), and three-way catalytic converter (TWC) on PAH emissions are investigated. Results show that the PAH emission concentrations increase 227-727%, 351-492%, and 155-408% by the increasing TO ratio, unworking SAS, and OS units in both motorcycles. For the PFi engine, the OCC unit is found to be more effective in PAH control (31-89%) than the SAS system (72-80%), especially under low TO operation. For the EFi engine which dominates the motorcycle market recently, the oxygen sensor for more accurate combustion control shows a better PAH reduction (36-76%) than TWC system (21-66%). The ultra-fine particulate phase PAHs, which is hardly removed by catalyst, needs to be further considered. Moreover, the total PAH emission level of the EFi engine is still about ten times higher than that of the PFi. By the annual emission calculation for three densely populated countries, the recent evolution significantly reduces the annual hydrocarbon (HC), carbon monoxide (CO), and nitrogen oxide (NOx) emissions but have unignorable PAH emissions. These emissions continuously affect the human health in the near-ground urban air and need to be considered in the next generation of motorcycle design., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Herein, we employ a galvanic replacement approach to create atomically dispersed Au on degradable zero-valent Cu nanocubes for tumor treatments on female mice. Controlling the addition of precursor HAuCl 4 allows for the fabrication of different atomic ratios of Au x Cu y . X-ray absorption near edge spectra indicates that Au and Cu are the predominant oxidation states of zero valence. This suggests that the charges of Au and Cu remain unchanged after galvanic replacement. Specifically, Au 0.02 Cu 0.98 composition reveals the enhanced •OH generation following O 2  → H 2 O 2  → •OH. The degradable Au 0.02 Cu 0.98 released Cu + and Cu 2+ resulting in oxygen reduction and Fenton-like reactions. Simulation studies indicate that Au single atoms boot zero-valent copper to reveal the catalytic capability of Au 0.02 Cu 0.98 for O 2  → H 2 O 2  → •OH as well. Instead of using endogenous H 2 O 2 , H 2 O 2 can be sourced from the O 2 in the air through the use of nanocubes. Notably, the Au 0.02 Cu 0.98 structure is degradable and renal-clearable., (© 2022. The Author(s).)

Long-term reanalysis data were used to assess inter-decadal to decadal modulations of the North Equatorial Current (NEC) bifurcation in the Pacific after the early 1990s. The wind stress curl anomaly (WSCA) in the region of 10° N-15° N and 160° E-170° E (C-BOX) had been found to excite Rossby waves and control NEC bifurcation along the Philippine coast. Our analysis revealed that the WSCA in the C-BOX has been remotely modulated by the Southern Annular Mode (SAM) since the early 1990s. It is shown that the SAM shifted to its positive phase at this transition and began strongly impacting the WSCA in the C-BOX and the NEC bifurcation. During the positive SAM phase after the early 1990s, strong climate variability occurred in the tropical to subtropical area of the North Pacific, with a clear footprint connected to the Antarctic region. Consistent with that finding, we determined that during the positive SAM phase, a dipole sea surface temperature pattern was generated in the South Pacific; this induced an atmospheric Rossby wave train in upper-level wind shear that propagated northward to the North Pacific. Such effects further enhanced downward motion and divergence at the surface, intensifying the easterlies in the equatorial area and the anticyclonic WSCA in the C-BOX. The anticyclonic WSCA in the C-BOX substantially excited downwelling oceanic Rossby waves at the surface, inducing an equatorward trend of NEC bifurcation after the early 1990s., (© 2022. The Author(s).)

Purpose: To investigate correlations between clinical and histopathologic characteristics of idiopathic epiretinal membrane (ERM)., Design: Retrospective interventional case series., Participants: In total, 87 eyes from 87 patients with idiopathic ERM who underwent pars plana vitrectomy with peeling of the ERM from 2019 to 2020 were included., Methods: The outcomes of clinical ophthalmic examination, including measurement of best-corrected visual acuity (BCVA) and spectral-domain OCT (SD-OCT), before and after surgery were reviewed. Surgical specimens were fixed in formalin and embedded in paraffin for histologic and immunohistochemical analysis., Main Outcomes Measures: The association between morphological characteristics revealed on SD-OCT images and the cellular composition of the surgically excised ERM demonstrated with immunohistochemical staining were the main outcome measures. Changes in the BCVA and central macular thickness (CMT) were assessed through a comparison of preoperative and postoperative measurements., Results: Based on SD-OCT morphological characteristics in the foveal area, 15 cases were classified into group 1A (mainly outer retinal thickening), 39 into group 1B (more tenting of the outer retina and distorted inner retina), and 33 into group 1C (prominent inner retina thickening). Overall, postoperative final BCVA and CMT at 1 year improved in all groups. Patients who presented with a better initial BCVA exhibited a more favorable final BCVA. Epiretinal membranes in group 1C demonstrated the greatest decrease in CMT compared with those in groups 1B and 1A, but the final CMT did not differ among the groups. A negative correlation between the density of hyalocytes (P = 0.003) and myofibroblasts (P = 0.047) was noted between the 3 groups. Total cell density and glial cell density of the ERMs were strongly associated with poor final BCVA and BCVA improvement., Conclusions: The present study provides new histopathologic information regarding the formation and progression of idiopathic ERM. Glial cell proliferation plays a predominant role in these processes. Epiretinal membranes with high cellularity and glial cell density may cause damage to the retina structure, resulting in poor postoperative visual outcomes. These findings provide additional evidence supporting early surgical intervention in patients with idiopathic ERM reported with visual disturbance., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Context: Qiangli Wuhu (QLWH) mixture is a concoction approved and registered by Ningxia Medical Products Administration. It has therapeutic effects on various types of pneumonia., Objective: To clarify the mechanisms of QLWH in treating pneumonia., Materials and Methods: The potential targets of QLWH in the treatment of pneumonia were predicted by network pharmacology. Male, Institute of Cancer Research (ICR) mice were randomly divided into five groups of 12 mice, control, vehicle, QLWH (10 and 20 mg/kg) and dexamethasone (DXM), and orally treated twice daily with normal saline, QLWH or DXM. The pneumonia model was established by tracheal instillation of lipopolysaccharide (LPS). After treatment five days, ELISA, H&E staining and Western blot were used to investigate protective effects of QLWH., Results: Nine hundred and ninety-four active ingredients were found through network pharmacology, corresponding to 135 targets for the treatment of pneumonia; compared to the vehicle group, QLWH (10 and 20 mg/kg) significantly decreased the levels of TNF-α (14.3% and 28.8%), IL-1β (23.9% and 42.8%) and IL-6 (13.2% and 16.1%), increased the levels of IL-10 (134.3% and 172.9%); in terms of mechanism, QLWH down-regulated TLR4/NF-κB/NLRP3 axis related proteins in lung tissue of pneumonia model mice ( p  < 0.05)., Discussion and Conclusions: This study combined network pharmacology and animal experiments, providing effective evidence for the clinical promotion of QLWH. Meanwhile, it is of significance for further development.

An indole-indanedione-based small molecule, compound 1Me, comprising an intramolecular C-H⋅⋅⋅O hydrogen-bond (H-bond) and with an intramolecular charge transfer (ICT) characteristic was prepared for the colorimetric and fluorometric detection of CN - . Compound 1Me is virtually nonfluorescent in solution but emits a strong yellow fluorescence in the solid state because of the intramolecular C-H⋅⋅⋅O H-bond, which inhibits the free rotation of the exocyclic C-C single bond of 1Me. The nucleophilic addition of CN - to the β-conjugated carbon of the indanedione group of 1Me, which breaks the intramolecular C-H⋅⋅⋅O H-bond and blocks ICT, causes the colorimetric and fluorometric responses of 1Me to CN - . Furthermore, inexpensive and portable paper-based test kits containing 1Me could be used to rapidly and conveniently sense CN - using the naked eye in real time. The results provide a new strategy for designing colorimetric and fluorometric cyanide-selective sensors based on an intramolecular C-H⋅⋅⋅O hydrogen bonded solid emitter., (© 2022 Wiley-VCH GmbH.)

Immune checkpoint (IC) therapy has led to a breakthrough in cancer treatment. However, the interaction of ICs is controversial in glioma. We detected features of ICs using transcriptome data and a multicolor immunofluorescence assay. We discovered that B7-H3 increased with grade and age and predicted worse overall survival (OS) at the transcriptional and proteomic levels. VISTA and PD-L1 were associated with OS and grade at the RNA level. At the protein level, VISTA was primarily expressed in tumor cells and TAMs. B7-H3 and VISTA were positively correlated with PD-L1. There was a strong correlation between PD-L1 and CD3 and between VISTA and IBA-1. PD-L1 was coexpressed with T cells. VISTA was coexpressed with TAMs. In T cells, we found a strong correlation in ICs, which worsened in TAMs and tumor cells. In conclusion, B7-H3 is a vital prognostic target for immunotherapy. We provided a potential mechanism for the immunosuppressive microenvironment in glioma., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022. Published by Elsevier Inc.)

Carbonylative multi-component reactions (CMCR), having four or more kinds of starting materials, provide an efficient strategy for the preparation of polyfunctional carbonylated compounds. Diverse CMCR utilizing non-noble transition-metal catalysts have been developed. This review summarized and discussed the recent advances in non-noble metal-catalyzed carbonylative multi-component reactions., (© 2022 Wiley-VCH GmbH.)

Accurate photon phase control on a chip is essential to improve the expandability and stability of photonic integrated circuits (PICs). Here, we propose a novel, to the best of our knowledge, on-chip static phase control method in which a modified line is added close to the normal waveguide with a lower-energy laser. By controlling the laser energy and the position and length of the modified line, the optical phase can be precisely controlled with low loss and a three-dimensional (3D) path. Customizable phase modulation ranging from 0 to 2π is performed with a precision of λ/70 in a Mach-Zehnder interferometer. The proposed method can customize high-precision control phases without changing the waveguide's original spatial path, which is expected to control the phase and solve the phase error correction problem during processing of large-scale 3D-path PICs.

Mineral trioxide aggregates (MTA) have been widely used in endodontic treatments, but after some time, patients suffer tooth discoloration due to the use of bismuth oxide (Bi2O3) as a radiopacifier. Replacement of Bi2O3 with high energy ball-milled single (zirconia ZrO2; hafnia, HfO2; or tantalum pentoxide, Ta2O5) or binary oxide powder was attempted, and corresponding discoloration improvement was investigated in the present study. Bi2O3-free MTA is expected to exhibit superior discoloration. The radiopacity, diametral tensile strength, and discoloration of MTA-like cements prepared from the as-milled powder were investigated. Experimental results showed that MTA-like cements prepared using Ta2O5 exhibited a slightly higher radiopacity than that of HfO2 but had a much higher radiopacity than ZrO2. Milling treatment (30 min to 3 h) did not affect the radiopacities significantly. These MTA-like cements exhibited superior color stability (all measured ΔE00 < 1.0) without any perceptible differences after UV irradiation. MTA-like cements prepared using ZrO2 exhibited the best color stability but the lowest radiopacity, which can be improved by introducing binary oxide. Among the investigated samples, MTA-like cement using (ZrO2)50(Ta2O5)50 exhibited excellent color stability and the best overall performance with a radiopacity of 3.25 mmAl and a diametral tensile strength of 4.39 MPa.

Non-keratinizing nasopharyngeal carcinoma (NPC) is a malignancy with a poor prognosis for relapsing patients and those with metastatic disease. Here, we identify a novel disease mechanism of NPC which may be its Achilles' heel that makes it susceptible to immunotherapy. CD137 is a potent costimulatory receptor on activated T cells, and CD137 agonists strongly enhance anti-tumor immune responses. A negative feedback mechanism prevents overstimulation by transferring CD137 from T cells to CD137 ligand (CD137L)-expressing antigen presenting cells (APC) during cognate interaction, upon which the CD137-CD137L complex is internalized and degraded. We found ectopic expression of CD137 on 42 of 122 (34.4%) NPC cases, and that CD137 is induced by the Epstein-Barr virus latent membrane protein (LMP) 1. CD137 expression enables NPC to hijack the inbuilt negative feedback mechanism to downregulate the costimulatory CD137L on APC, facilitating its escape from immune surveillance. Further, the ectopically expressed CD137 signals into NPC cells via the p38-MAPK pathway, and induces the expression of IL-6, IL-8 and Laminin γ2. As much as ectopic CD137 expression may support the growth and spread of NPC, it may be a target for its immunotherapeutic elimination. Natural killer cells that express a CD137-specific chimeric antigen receptor induce death in CD137 + NPC cells, in vitro, and in vivo in a murine xenograft model. These data identify a novel immune escape mechanism of NPC, and lay the foundation for an urgently needed immunotherapeutic approach for NPC., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans and can present with highly variable clinical manifestations. Immune deficiencies occur because of thymic hypoplasia or aplasia., Methods: This retrospective study included patients diagnosed with 22q11.2DS at a medical center between 2000 and 2021. We analyzed the association between clinical phenotypes, immunological abnormalities, age, and outcomes., Results: Eighty-seven patients with 22q11.2DS had a median diagnostic age of 1.78 months. Patients presented with congenital heart disease (CHD; 86.2%), major infections (75.9%), and failure to thrive (FTT; 58.6%). Autoimmunity, neuropsychiatric disorders, and hypoparathyroidism were significantly associated. Neonatal seizures were associated with early diagnosis before 2 months (OR 8.56, 95% CI 1.21-60.58, P = 0.032). Immunological abnormalities included lymphopenia (93.1%), T lymphopenia (71.9%), CD4 + T lymphopenia (64.1%), a lack of hepatitis B vaccine antibodies (46.2%), and complete DiGeorge syndrome (cDGS) (2.3%). Severe lymphopenia and T lymphopenia improved at 3 years of age. Two patients with cDGS were treated with hematopoietic stem cell transplantation, and one survived. The mortality rate was 12.8% and the estimated 35-year survival probability was 77.5%. Major infections experienced > four times were significantly associated with a decreased survival rate of 60%. Patients with CHD without FTT or recurrent infections had a better 20-year survival rate (96.2%)., Conclusions: CHD, major infection, and FTT were common manifestations and poor prognostic factors. Autoimmunity, neuropsychiatric disorders, and hypoparathyroidism were significantly associated. Although T lymphopenia may improve with age, patients with 22q11.2DS require lifelong monitoring for immune dysregulation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Anhedonia is the core symptom of depression, which largely reflects the therapeutic effect of depression. Hypericum perforatum is one of the most important antidepressant herb that has fewer side effects than traditional antidepressants. Considering the antibacterial effect of Hypericum perforatum, we verified whether this antidepressant activity was related to intestinal microbiomics. So we established anhedonia mouse model to explore the underlying treatment mechanism of hyperforin, the key antidepressant ingredient of Hypericum perforatum and to screen new psychobiotics based on hyperforin. It was found that hyperforin prevented anhedonia induced by chronic restraint stress in mice and altered the richness and evenness of bacteria populations compared with stressed mice. Metastat analysis showed that Akkermansia muciniphila and Muribaculum intestinale were the bacterial species obviously affected by hyperforin, and their abundance in hyperforin-treated group significantly increased. The results suggest that the effect of hyperforin on anhedonia may be partly assisted by Akkermansia muciniphila. These also indicate that Muribaculum intestinale may be another important intestinal bacteria involved in the pathogenesis of anhedonia symptom and depression., (© 2022 The Society for Applied Microbiology.)

Background: Childhood asthma is an inflammatory disease with heterogeneous outcomes. We sought to determine the impact of total IgE, blood eosinophil, allergen sensitization, and inhaled corticosteroid (ICS) on longitudinal outcomes and to identify characteristics for discriminating different outcomes., Methods: We conducted a retrospective study in 383 childhood asthma patients and another 313 patients with blood eosinophil data only receiving regular program-based visits from September 1, 2004, to December 31, 2018. Peak expiratory flow (PEF) variability, PEF predicted %, asthma severity, and asthma control at each visit were assessed as clinical outcomes., Results: Our data show that the percentage of blood eosinophils was significantly associated with increased asthma severity (OR: 1.043, 95% CI: 1.002-1.086, P = 0.0392). Mold sensitization was significantly associated with asthma severity (OR: 2.2485, 95% CI: 1.3253-3.8150, P = 0.0027). Characteristics including sensitization status plus ICS dosage had the best area under the receiver operating characteristic curve (AUC) value for predicting longitudinal PEF predicted % (0.6609), PEF variability (0.6885), asthma severity (0.5918), and asthma control (0.6441), respectively., Conclusions: We showed that the risk for adverse clinical outcomes at follow-up differed between serum IgE, blood eosinophil, and allergen sensitization identified at baseline. Sensitization and ICS dosage were predictive characteristics of long-term clinical outcomes., Impact: The unique aspects of the study are its longitudinal assessment of patients receiving guideline-based asthma management program to help characterize the stability of the clinical outcomes over time. Characteristics including allergen sensitization and ICS dosage demonstrated an improved capability for distinguishing between better and worse clinical outcomes. Through longitudinal serial assessment, this study indicates the risk for adverse clinical outcomes differed between children with serum IgE/blood eosinophil/allergen sensitization characterized at baseline., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objectives: Observational studies have demonstrated associations between gout and hypertension, but whether they are causal remains unclear. Our work aims to assess the causal relationship between gout and hypertension., Methods: We obtained genetic information from the Taiwan Biobank, including 88,347 participants and 686,439 single-nucleotide polymorphisms (SNPs). A novel model of Mendelian randomisation (MR) with coarsened exposures was used to examine the causality between the liability of gout on hypertension and vice versa, using 4 SNPs associated with gout and 10 SNPs associated with hypertension after removal of SNPs associated with measured confounders. The binary exposure (gout/hypertension) can be considered a coarsened approximation of a latent continuous trait. The inverse-variance weighted (IVW) and polygenic risk score (PRS) methods were used to estimate effect size. The MR analysis with coarsened exposures was performed with and without adjustments for covariates., Results: Of the 88,347 participants, 3253 (3.68%) had gout and 11,948 (13.52%) had hypertension (men, 31.9%; mean age 51.1 [SD, 11.1] years). After adjusting to measured confounders, MR analysis with coarsened exposures showed a significant positive causal effect of the liability of gout on hypertension in both the IVW method (relative risk [RR], 1.10; 95% confidence interval [CI], 1.03-1.19; p = 0.0077) and the PRS method (RR, 1.10; 95% CI, 1.02-1.19; p = 0.0092). The result of causality was the same before and after involving measured confounders. However, there was no causal effect of the liability of hypertension on gout., Conclusions: In this study, we showed that the liability of gout has a causal effect on hypertension, but the liability of hypertension does not have a causal effect on gout. Adequate management of gout may reduce the risk of developing hypertension., (© 2022. The Author(s).)

Edge states in topological phase transitions have been observed in various platforms. To date, verification of the edge states and the associated topological invariant are mostly studied, and yet a quantitative measurement of topological phase transitions is still lacking. Here, we show the direct measurement of edge states and their localization lengths from survival probability. We employ photonic waveguide arrays to demonstrate the topological phase transitions based on the Su-Schrieffer-Heeger model. By measuring the survival probability at the lattice boundary, we show that in the long-time limit, the survival probability is P=(1-e^{-2/ξ&#95;{loc}})^{2}, where ξ&#95;{loc} is the localization length. This length derived from the survival probability is compared with the distance from the transition point, yielding a critical exponent of ν=0.94±0.04 at the phase boundary. Our experiment provides an alternative route to characterizing topological phase transitions and extracting their key physical quantities.

Neonatal infection with nonpolio enteroviruses (EVs) causes nonspecific febrile illnesses and even life-threatening multiorgan failure. Hepatitis, which often results in hepatic necrosis followed by disseminated intravascular coagulopathy, is one of the most severe and frequent fatal neonatal EV infection complications. Coxsackievirus B (CVB) 1-5 and many echoviruses have been most commonly identified. Neonatal EV infection treatment has usually involved initial supportive care. Studies for CVB and echovirus infection treatments were developed for more than thirty years. Intravenous immunoglobulin and pleconaril therapy was performed in some clinical trials. Additionally, other studies demonstrated antiviral and/or anti-inflammatory pathogenesis mechanisms of neonatal EV hepatitis in in vitro or in vivo models. These treatments represented promising options for the clinical practice of neonatal EV hepatitis. However, further investigation is needed to elucidate the whole therapeutic potential and safety problems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Tsai, Chen and Wang.)

Since the outbreak of COVID-19, mask wearing has become a global phenomenon. How do masks influence wearers' behavior in everyday life? We examine the effect of masks on wearers' deviant behavior in China, where mask wearing is mostly a public-health issue rather than a political issue. Drawing on behavioral ethics research, we test two competing hypotheses: (a) masks disinhibit wearers' deviant behavior by increasing their sense of anonymity and (b) masks are a moral symbol that reduces wearers' deviant behavior by heightening their moral awareness. The latter hypothesis was consistently supported by 10 studies (including direct replications) using mixed methods (e.g., traffic camera recording analysis, observational field studies, experiments, and natural field experiment) and different measures of deviant behavior (e.g., running a red light, bike parking in no-parking zones, cheating for money, and deviant behavior in the library). Our research ( n = 68,243) is among the first to uncover the psychological and behavioral consequences of mask wearing beyond its health benefits.

Introduction: Segmental eight-point bioimpedance has been increasingly used in practice. However, whether changes in bioimpedance analysis components before and after hemodialysis (HD) using this technique in a standing position is comparable to traditional whole-body wrist-to-ankle method is still unclear. We aimed to investigate the differences between two eight-point devices (InBody 770 and Seca mBCA 514) and one wrist-to-ankle (Hydra 4200) in HD patients and healthy subjects in a standing position., Methods: Thirteen HD patients were studied pre- and post-HD, and 12 healthy subjects once. Four measurements were performed in the following order: InBody; Seca; Hydra; and InBody again. Electrical equivalent models by each bioimpedance method and the fluid volume estimates by each device were also compared., Findings: Overall, total body water (TBW) was not different between the three devices, but InBody showed lower extracellular water (ECW) and higher intracellular water (ICW) compared to the other two devices. When intradialytic weight loss was used as a surrogate for changes in ECW (∆ECW) and changes in TBW (∆TBW), ∆ECW was underestimated by Hydra (-0.79 ± 0.89 L, p < 0.01), InBody (-1.44 ± 0.65 L, p < 0.0001), and Seca (-0.32 ± 1.34, n.s.). ∆TBW was underestimated by Hydra (-1.14 ± 2.81 L, n.s.) and InBody (-0.52 ± 0.85 L, p < 0.05) but overestimated by Seca (+0.93 ± 3.55 L, n.s.)., Discussion: Although segmental eight-point bioimpedance techniques provided comparable TBW measurements not affected by standing over a period of 10-15 min, the ECW/TBW ratio appeared to be significantly lower in InBody compared with Seca and Hydra. Results from our study showed lack of agreement between different bioimpedance devices; direct comparison of ECW, ICW, and ECW/TBW between different devices should be avoided and clinicians should use the same device to track the fluid status in their HD population in a longitudinal direction., (© 2022 International Society for Hemodialysis.)

Angiostrongylus cantonensis, the causative agent of human eosinophilic meningitis and eosinophilic meningoencepalitis, has been reported to cause cognitive impairments in the host. To determine whether drug treatment improves the cognitive functions, BALB/c mice infected with 50 third-stage larvae were treated with albendazole, dexamethasone, or co-therapy since day 7 or 14 post-infection for one or two weeks. Abilities of spatial memory and learning of these animals were assessed with the Morris water maze. Our results showed that body weight was significant higher then infected group in the albendazole and combined therapy groups. Significantly lower worm recovery rates were found in mice treated with the same groups. The mice treated with dexamethasone since day 7 for 14 day had significant longer time in the remaining groups were found in forced swimming test. The animals treated with albendazole and combined therapy since day 7 for 14 days was demonstrated to have significantly shorter latencies to the platform in learning memory on day 3 and 4. Mice in these two groups were demonstrated to have significantly higher sores in spatial memory tests. These results indicate that treatment with albendazole or combined therapy may be more efficient in preventing brain damages and depression as well as preserving their capabilities in learning and memory. Therefore, administration of albendazole alone or combined with dexamethasone should have higher efficacies than dexamethasone alone in treatment of BALB/c mice infected with a heavy dose of 50 third-stage larvae of A. cantonensis., Competing Interests: Declaration of competing interest The author declares that there is no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)