CYCLOIDEA-like genes control floral symmetry, floral orientation, and nectar guide patterning.

Actinomorphic flowers usually orient vertically (relative to the horizon) and possess symmetric nectar guides, while zygomorphic flowers often face horizontally and have asymmetric nectar guides, indicating that floral symmetry, floral orientation, and nectar guide patterning are correlated. The origin of floral zygomorphy is dependent on the dorsoventrally asymmetric expression of CYCLOIDEA (CYC)-like genes. However, how horizontal orientation and asymmetric nectar guides are achieved remains poorly understood. Here, we selected Chirita pumila (Gesneriaceae) as a model plant to explore the molecular bases for these traits. By analyzing gene expression patterns, protein-DNA and protein-protein interactions, and encoded protein functions, we identified multiple roles and functional divergence of 2 CYC-like genes, i.e. CpCYC1 and CpCYC2, in controlling floral symmetry, floral orientation, and nectar guide patterning. CpCYC1 positively regulates its own expression, whereas CpCYC2 does not regulate itself. In addition, CpCYC2 upregulates CpCYC1, while CpCYC1 downregulates CpCYC2. This asymmetric auto-regulation and cross-regulation mechanism might explain the high expression levels of only 1 of these genes. We show that CpCYC1 and CpCYC2 determine asymmetric nectar guide formation, likely by directly repressing the flavonoid synthesis-related gene CpF3'5'H. We further suggest that CYC-like genes play multiple conserved roles in Gesneriaceae. These findings shed light on the repeated origins of zygomorphic flowers in angiosperms.

Neurocomputational Substrates Underlying the Effect of Identifiability on Third-Party Punishment.

The identifiable target effect refers to the preference for helping identified victims and punishing identifiable perpetrators compared with equivalent but unidentifiable counterparts. The identifiable target effect is often attributed to the heightened moral emotions evoked by identified targets. However, the specific neurocognitive processes that mediate and/or modulate this effect remain largely unknown. Here, we combined a third-party punishment game with brain imaging and computational modeling to unravel the neurocomputational underpinnings of the identifiable transgressor effect. Human participants (males and females) acted as bystanders and punished identified or anonymous wrongdoers. Participants were more punitive toward identified wrongdoers than anonymous wrongdoers because they took a vicarious perspective of victims and adopted lower reference points of inequity (i.e., more stringent norms) in the identified context than in the unidentified context. Accordingly, there were larger activity of the ventral anterior insula, more distinct multivariate neural patterns in the dorsal anterior insula and dorsal anterior cingulate cortex, and lower strength between ventral anterior insula and dorsolateral PFC and between dorsal anterior insula and ventral striatum connectivity in response to identified transgressors than anonymous transgressors. These findings implicate the interplay of expectancy violations, emotions, and self-interest in the identifiability effect. Last, individual differences in the identifiability effect were associated with empathic concern/social dominance orientation, activity in the precuneus/cuneus and temporo-parietal junction, and intrinsic functional connectivity of the dorsolateral PFC. Together, our work is the first to uncover the neurocomputational processes mediating identifiable transgressor effect and to characterize psychophysiological profiles modulating the effect.SIGNIFICANCE STATEMENT The identifiable target effect, more help to identified victims or stronger punishment to identifiable perpetrators, is common in daily life. We examined the neurocomputational mechanisms mediating/modulating the identifiability effect on third-party punishment by bridging literature from economics and cognitive neuroscience. Our findings reveal that identifiable transgressor effect is mediated by lower reference points of inequity (i.e., more stringent norms), which might be associated with a stronger involvement of the emotion processes and a weaker engagement of the analytic/deliberate processes. Furthermore, personality traits, altered brain activity, and intrinsic functional connectivity contribute to the individual variance in the identifiability effect. Overall, our study advances the understanding of the identifiability effect by shedding light on its component processes and modulating factors.

Identification, characterization and application of M16AT, a new organic solvent-tolerant (R)-enantio-selective type IV amine transaminase from Mycobacterium sp. ACS1612.

Biocatalysis has emerged as a powerful alternative to traditional chemical methods, especially for asymmetric synthesis. As biocatalysts usually exhibit excellent chemical, regio- and enantioselectivity, they facilitate and simplify many chemical processes for the production of a broad range of products. Here, a new biocatalyst called, R-selective amine transaminases (R-ATAs), was obtained from Mycobacterium sp. ACS1612 (M16AT) using in-silico prediction combined with a genome and protein database. A two-step simple purification process could yield a high concentration of pure enzyme, suggesting that industrial application would be inexpensive. Additionally, the newly identified and characterized R-ATAs displayed a broad substrate spectrum and strong tolerance to organic solvents. Moreover, the synthetic applicability of M16AT has been demonstrated by the asymmetric synthesis of (R)-fendiline from of (R)-1-phenylethan-1-amine.

Inhibition of HMGB1 improves experimental mice colitis by mediating NETs and macrophage polarization.

OBJECTIVE: Inflammatory bowel disease (IBD) is listed by the World Health Organization as one of the modern intractable diseases. High mobility histone box 1 (HMGB1), originally described as a non-histone nucleoprotein involved in transcriptional regulation, was later identified as a pro-inflammatory cytokine that may contribute to the pathogenesis of inflammatory diseases such as IBD. Neutrophil extracellular traps (NETs) play an important role in the pathophysiology of IBD The aim of this study was to investigate the role of HMGB1 in experimental colitis mice and its potential mechanisms of action. METHODS: We first constructed the experimental colitis mouse model. Intervention of mice by rhHMGB1 supplementation or HMGB1 inhibition. The pathological morphology of the colon was observed using HE staining. Apoptosis of colonic tissue intestinal epithelial cells was evaluated using Tunel assay. The expression of HMGB1, ZO-1 and occludin in colon tissue was detected by immunohistochemistry, ELISA and western-blot. We also assessed the effects of HMGB1 on colonic injury, NETs content, macrophage polarization and inflammatory cells in mice. The regulatory effect of HMGB1 inhibition on NETs was assessed by combining DNase I. RESULTS: Inhibition of HMGB1 significantly reduced the inflammatory model in experimental colitis mice, as evidenced by reduced body weight, increased colonic length, reduced DAI scores and apoptosis, reduced inflammatory response, and improved colonic histopathological morphology and intestinal mucosal barrier function. Meanwhile, inhibition of HMGB1 was able to reduce the expression of CD86, citH3 and MPO and increase the expression of CD206 in the colonic tissue of mice. In addition, DNase I intervention was also able to improve colonic inflammation in mice. And the best effect was observed when DNase I and inhibition of HMGB1 were intervened together. CONCLUSION: Inhibition of HMGB1 ameliorates IBD by mediating NETs and macrophage polarization.

CXCL6 promotes the progression of NAFLD through regulation of PPARα.

An increasing number of studies have shown that Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity, insulin resistance, dyslipidemia, hypertension and metabolic syndrome, but its specific pathogenesis remains unclear. By analyzing GEO database, we found CXCL6 was upregulated in liver tissues of patients with NAFLD. We also confirmed with qPCR that CXCL6 is highly expressed in serum of patients with NAFLD. To identify the underlying impact of CXCL6 on NAFLD, we established animal and cell models of NAFLD. Similarly, we confirmed by qPCR and Western blot that CXCL6 was upregulated in the NAFLD model in vitro and vivo. After transfecting NAFLD cells with siRNA targeting CXCL6 (si-CXCL6), a series of functional experiments were carried out, and these data indicated that the inhibition of CXCL6 reduced intracellular lipid deposition, decreased AST, ALT and TG level, facilitate cell proliferation and suppress their apoptosis. Furthermore, western blot and qPCR analyses displayed that the suppression of CXCL6 could raise the PPARα expression, but PPAR α inhibitor, GW6471 could partially counteract this effect. What's more, Oil Red O staining, biochemical analyzer and TG detection kit revealed that GW6471 could reverse the inhibitory effect of si-CXCL6 on NAFLD. In summary, we provide convincing evidence that CXCL6 is markedly elevated in NAFLD, and the CXCL6/PPARα regulatory network mediates disease progression of NAFLD.

Psychometric properties and measurement invariance of the Chinese version of the cognitive emotion regulation questionnaire-short in patients with cancer.

OBJECTIVE: The study aimed to evaluate the psychometric properties and measurement invariance (MI) of the Chinese version of the cognitive emotion regulation questionnaire-short (CERQ-short) in cancer patients. METHODS: This cross-sectional study included 505 cancer patients from mainland China. In addition to sociodemographic and clinical characteristics, the CERQ-short and the distress thermometer were included in the study measures. RESULTS: Item analysis indicated a promising result. And the results of CFA indicated that the CERQ-short demonstrated satisfactory factorial validity in cancer patients. Cronbach's alpha coefficients were between 0.663 and 0.910, while McDonald's omega coefficients were between 0.664 and 0.910. The CERQ-short had sufficient convergent, discriminant and concurrent validity among cancer patients. Lastly, MI supported that the CERQ-short demonstrated strong measurement equivalence across gender, residence and age. CONCLUSIONS: This study shows that the Chinese version of the CERQ-short has convincing psychometric properties and MI, which supports its use in cancer patients.

The effectiveness of positive psychological interventions for patients with cancer: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: To evaluate the effectiveness of positive psychological interventions on quality of life, positive psychological outcomes and negative psychological outcomes in patients with cancer. BACKGROUND: Patients with cancer often suffer from various psychological problems and have a poor quality of life. Positive psychological interventions have been increasingly applied to patients with cancer, but the results of these studies have not been synthesized. DESIGN: A systematic review and meta-analysis of randomized controlled trials according to PRISMA. METHODS: Six English databases and four Chinese databases were searched from the inception to December 2022. Two reviewers independently assessed the risk of bias using the Cochrane Risk of Bias tool. RevMan was used for meta-analysis. RESULTS: Twenty-nine randomized controlled trials examined the effects of positive psychological interventions including meaning therapy, dignity therapy, positive psychotherapy, mindfulness- based intervention, life review, expressive writing intervention, acceptance and commitment psychotherapy, attention and interpretation therapy, compassion training and spiritual therapy on patients with cancer. Positive psychological interventions significantly improved the quality of life, enhanced positive psychological outcomes including well-being, meaning of life, self-esteem, optimism, resilience and self-efficacy and alleviated negative psychological outcomes including depression, anxiety and hopelessness. However, the heterogeneity of some outcomes was rather high, due to the wide diversity of the interventions included. CONCLUSION: Positive psychological interventions have potentially positive effects on improving quality of life, enhancing positive psychological outcomes and alleviating negative psychological outcomes in patients with cancer. However, due to the heterogeneity and the lack of follow-up studies, more high-quality studies are needed to confirm the results of our review and to clarify the long-term effects of positive psychological interventions. RELEVANCE TO CLINICAL PRACTICE: As feasible psychological interventions, healthcare professionals can consider applying appropriate positive psychological interventions according to the condition of cancer patients. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

PA200-Mediated Proteasomal Protein Degradation and Regulation of Cellular Senescence.

Cellular senescence is closely related to DNA damage, proteasome inactivity, histone loss, epigenetic alterations, and tumorigenesis. The mammalian proteasome activator PA200 (also referred to as PSME4) or its yeast ortholog Blm10 promotes the acetylation-dependent degradation of the core histones during transcription, DNA repair, and spermatogenesis. According to recent studies, PA200 plays an important role in senescence, probably because of its role in promoting the degradation of the core histones. Loss of PA200 or Blm10 is a major cause of the decrease in proteasome activity during senescence. In this paper, recent research progress on the association of PA200 with cellular senescence is summarized, and the potential of PA200 to serve as a therapeutic target in age-related diseases is discussed.

[Clinical comprehensive evaluation of Shexiang Tongxin Dropping Pills].

Based on literature and questionnaire research, related evidence and related data on Shexiang Tongxin Dropping Pills were collected in terms of safety, effectiveness, economy, innovation, suitability, and accessibility. In addition, multi-criteria decision analysis(MCDA) model was used to comprehensively evaluate the clinical value of Shexiang Tongxin Dropping Pills. Quality control was carried out strictly based on evidence-based medicine evaluation. Shexiang Tongxin Dropping Pills were recommended for stable fatigue angina of coronary heart disease with Qi deficiency and blood stasis by guidelines and experts. The conventional treatment of western medicine adds Shexiang Tongxin Dropping Pills to reduce the frequency of angina attacks, shorten the duration, improve exercise tolerance, and improve the quality of life and Chinese symptoms, and the effectiveness is rated as grade A. Adverse reactions are mostly general adverse reactions, and no serious adverse reactions have been reported, consistent with the known risks listed in the instruction for adverse events, contraindications, and precautions. The safety is rated as grade A, and the daily cost is 7.74 yuan. The cost-effectiveness shows that it is a treatment regimen with pharmacoeconomic advantages, and the economic performance is rated as grade A. According to specialist research, Shexiang Tongxin Dropping Pills have good clinical innovation and service innovation, and innovation is rated as grade A. There are no special storage conditions, medicinal material ingredients, or other restrictions, and the clinical use meets the specifications of the medication guidelines. The suitability is rated as grade A. The price level, availability, and affordability of drugs are generally good, and the accessibility is rated as grade A. The clinical value of Shexiang Tongxin Dropping Pills is great.

[Guidelines for economic evaluation of post-marketing Chinese patent medicine].

With the premise of drug safety and effectiveness, pharmacoeconomic evaluation can provide optimal solutions for diversified decision-making application scenarios from different research perspectives while maximizing the rational utilization of existing healthcare resources. Chinese patent medicine is an essential component of pharmaceutical utilization in China and a significant part of healthcare expenditure in China. However, the economic evaluation of post-marketing Chinese patent medicine is lacking. These evaluations often lack standardization, exhibit varying quality, and are unable to effectively support healthcare decisions, indicating a need for improvement in overall quality. Given this situation, this project has gathered leading experts from China and has strictly adhered to the requirements of the group standards set by the China Association of Traditional Chinese Medicine in developing Guidelines for economic evaluation of post-marketing Chinese patent medicine, aiming to provide methodological guidance for the post-market pharmacoeconomic evaluation of Chinese patent medicine, enhancing the standardization of pharmacoeconomic evaluations of Chinese patent medicine and the scientific validity of research results, and thereby elevating the overall quality of pharmacoeconomic evaluations for post-marketing Chinese patent medicine. The guidelines adhere to the framework provided by relevant laws and regulations in China and technical guidance documents. It is based on guidance from traditional Chinese medicine(TCM) theories, focusing on the unique characteristics of TCM. It covers various aspects of pharmacoeconomic evaluation, including fundamental principles, research topic selection, research question definition, study design type selection, cost identification and measurement, health outcomes, and evaluation methods. The guidelines offer methodological recommendations and decision guidance to address common issues and challenges in the pharmacoeconomic evaluation of post-marketing Chinese patent medicine.

[A new sesquiterpene from Syringa oblata].

In this study, the chemical components of ethanol extract from the aromatic parts of Syringa oblata were systematically separated and purified by silica gel column chromatography, thin layer plate preparation and liquid phase preparation. Combined with ultraviolet analyzer(UV), infrared analyzer(IR), nuclear magnetic resonance analyzer(NMR), high resolution mass spectrometer(HR-ESI-MS), X-ray diffraction and other spectrum technology as well as literature physicochemical data comparison methods for structural identification, a total of 10 compounds were identified. They were identified as oblatanoid D(1),(-)-T-muurolol(2), oblatanoid E-G(3-5), 14-noreudesma-3-hydroxy-3-en-2,9-dione(6), 1-isopropyl-2,7-dimethylnaphthalene(7), isocoradiol(8), α-calacorene(9), cadin-4-en-1-ß-ol(10). Compound 1 is a new sesquiterpene compound that has not been reported, and the other 9 compounds are isolated from S. oblata for the first time. The compound 1 has a significant protective effect on the LPS-induced inflammatory injury model of RAW264.7 cells.

The hybridization origin of the Chinese endemic herb genus Notopterygium (Apiaceae): Evidence from population genomics and ecological niche analysis.

Hybridization is recognized as a major force in species evolution and biodiversity formation, generally leading to the origin and differentiation of new species. Multiple hybridization events cannot easily be reconstructed, yet they offer the potential to study a number of evolutionary processes. Here, we used nuclear expressed sequence tag-simple sequence repeat and large-scale single nucleotide polymorphism variation data, combined with niche analysis, to investigate the putative independent hybridization events in Notopterygium, a group of perennial herb plants endemic to China. Population genomic analysis indicated that the four studied species are genetically well-delimited and that N. forrestii and N. oviforme have originated by hybridization. According to Approximate Bayesian Computation, the best-fit model involved the formation of N. forrestii from the crossing of N. franchetii and N. incisum, with N. forrestii further backcrossing to N. franchetii to form N. oviforme. The niche analyses indicated that niche divergence [likely triggered by the regional climate changes, particularly the intensification of East Asian winter monsoon, and tectonic movements (affecting both Qinghai-Tibetan Plateau and Qinling Mountains)] may have promoted and maintained the reproductive isolation among hybrid species. N. forrestii shows ecological specialization with respect to their parental species, whereas N. oviforme has completely shifted its niche. These results suggested that the climate and environmental factors together triggered the two-step hybridization of the East Asia herb plants. Our study also emphasizes the power of genome-wide SNPs for investigating suspected cases of hybridization, particularly unravelling old hybridization events.

The transcription factor BnaWRKY10 regulates cytokinin dehydrogenase BnaCKX2 to control cytokinin distribution and seed size in Brassica napus.

Cytokinins (CKs) are phytohormones that promote cell division and differentiation. However, the regulation of CK distribution and homeostasis in Brassica napus is poorly understood. Here, the endogenous CKs were first quantified by LC-ESI-MS/MS in rapeseed tissues and visualized by TCSn::GUS reporter lines. Interestingly, the cytokinin oxidase/dehydrogenase BnaCKX2 homologs were mainly expressed in reproductive organs. Subsequently, the quadruple mutants of the four BnaCKX2 homologs were generated. Endogenous CKs were increased in the seeds of the BnaCKX2 quadruple mutants, resulting in a significantly reduced seed size. In contrast, overexpression of BnaA9.CKX2 resulted in larger seeds, probably by delaying endosperm cellularization. Furthermore, the transcription factor BnaC6.WRKY10b, but not BnaC6.WRKY10a, positively regulated BnaA9.CKX2 expression by binding directly to its promoter region. Overexpression of BnaC6.WRKY10b rather than BnaC6.WRKY10a resulted in lower concentration of CKs and larger seeds by activating BnaA9.CKX2 expression, indicating that the functional differentiation of BnaWRKY10 homologs might have occurred during B. napus evolution or domestication. Notably, the haploid types of BnaA9.CKX2 were associated with 1000-seed weight in the natural B. napus population. Overall, the study reveals the distribution of CKs in B. napus tissues, and shows that BnaWRKY10-mediated BnaCKX2 expression is essential for seed size regulation, providing promising targets for oil crop improvement.

The dynamics of lncRNAs transcription in interspecific F1 allotriploid hybrids between Brassica species.

Interspecific hybridization is the intrinsic forces behind genome evolution. Long non-coding RNAs (lncRNAs) are important for plant biological processes regulation. However, it is unclear that these non-coding fractions are impacted by interspecific hybridization. Here we examined the profiles of lncRNAs by comparing them with coding genes in Brassica napus, three accessions of Brassica rapa, and their F1 hybrids. 6206 high-confidential lncRNAs were identified in F 1 hybrids and their parentals, and the lncRNAs transcriptome in the F1 hybrids was reprogrammed by the genome shock. Notably, genome-wide unbalanced of lncRNAs were observed between An and Ar subgenomes, ELD (Expression Level Dominance) was biased toward the An -genome in F1 hybrids, and ELD of non-conserved lncRNAs was more than conserved lncRNAs. Our findings demonstrate that the reprogramed lncRNAs acts as important role in enhancing plant plasticity, leading to the acquisition of desirable traits in polyploid Brassica species.

Assessment of mandibular retromolar space in adults with regard to third molar eruption status.

OBJECTIVE: The aim of this study was to compare the difference in length and width of the mandibular retromolar space (RMS) stratified by the different eruption and impaction statuses of the third molars in patients with skeletal Class I malocclusion. MATERIALS AND METHODS: The right mandibular RMS in 186 adult patients categorized according to the different statuses of the third molar was analyzed by using cone-beam computed tomography (CBCT). The shortest distances between the inner lingual cortex of the mandibular body and second molar root were measured parallel to the posterior occlusal line (POL) at depths of 2, 4, 6, 8, and 10 mm (mandibular retromolar space length in root level, RLin2,4,6,8,10) on the axial slices with the cementoenamel junction (CEJ) as the reference level. The width of the RMS and second molar root was measured vertical to the POL at the terminal point of the molar distalization at depths of 2, 4, 6, 8, and 10 mm (width of the mandibular retromolar space, BW2,4,6,8,10/ width of the second molar distal root, TW2,4,6,8,10) from the CEJ. RESULTS: RL in different measurement planes was 2.72 ± 2.22 ~ 3.74 ± 2.26 for Group A, 5.27 ± 1.68 ~ 9.10 ± 2.04 for Group B, 1.94 ± 2.34 ~ 5.71 ± 4.37 for Group C, 1.83 ± 2.95 ~ 5.05 ± 4.24 for Group D, and 5.93 ± 3.97 ~ 10.52 ± 2.16 for Group E. The BW measurement results for A ~ E group were 9.71 ± 1.41 ~ 10.51 ± 1.81, 9.83 ± 1.39 ~ 12.55 ± 2.11, 9.96 ± 1.21 ~ 12.17 ± 1.62, 9.82 ± 1.47 ~ 12.28 ± 2.77, and 10.02 ± 1.20 ~ 12.75 ± 0.82, respectively. There was no significant difference between men and women in any measurements (P > 0.05). Patients with normal third molars erupted and those vertically impacted possessed larger RMS lengths than those in which the third molars were missing, horizontally impacted or mesially impacted (P < 0.05). In each measurement plane, TW was significantly smaller than BW (P < 0.05). CONCLUSIONS: Sex had no effect on the length or width of the mandibular RMS. Different statuses of third molars can also differentially affect the mandibular RMS. The mandibular RMS width is not a limit for mandibular molar distalization. CLINICAL RELEVANCE: When considering the distalization of mandibular molars, more attention should be directed to the lingual cortex of the mandible, and CBCT scans are recommended for patients who require significant mandibular molar distalization. The mandible buccal shelf and retromolar area maybe a safe zone to insert the miniscrew for molar distalization.

OUTCOMES OF AUTOTRANSPLANTED THIRD MOLARS WITH COMPLETE ROOT FORMATION: A SYSTEMIC REVIEW AND META-ANALYSIS.

OBJECTIVES: Clear evidence is lacking regarding the outcomes of autogenous tooth transplantation (ATT) of third molars with complete root formation. The current review aims to explore the long-term survival and complication rates. METHODS: A comprehensive search was performed in December 2022 of the PubMed, Scopus, Embase, EBSCO, Ovid, Science Direct, and Web of Science databases. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered at the International Prospective Register of Systematic Reviews (CRD42022337659). The pooled survival, root resorption, and ankyloses rates were calculated. Subgroup analyses were performed to explore the effects of sample size and 3D techniques. RESULTS: Twelve studies from 5 countries fulfilled the eligibility, with 759 third molars transplanted in 723 patients. Five studies reported 100% survival at 1-year follow-up. After excluding these 5 studies, the pooled survival rate was 93.62% at 1 year. The survival rate of 1 large sample study was significantly higher than that of small ones at 5 years. The complications of studies using 3D techniques were: root resorption 2.06% (95% CI: 0.22, 7.50) and ankyloses 2.81% (95% CI: 0.16, 12.22), compared to those without 3D techniques: root resorption 10.18% (95% CI: 4.50, 17.80) and ankyloses 6.49% (95% CI: 3.45, 10.96). CONCLUSIONS: ATT of third molars with complete root formation is a reliable alternative for replacement of a missing tooth and has a promising survival rate. The use of 3D techniques can reduce complication rates and improve long-term survival.

Proteasome subunit α4s is essential for formation of spermatoproteasomes and histone degradation during meiotic DNA repair in spermatocytes.

Meiosis, which produces haploid progeny, is critical to ensuring both faithful genome transmission and genetic diversity. Proteasomes play critical roles at various stages of spermatogenesis, including meiosis, but the underlying mechanisms remain unclear. The atypical proteasomes, which contain the activator PA200, catalyze the acetylation-dependent degradation of the core histones in elongated spermatids and DNA repair in somatic cells. We show here that the testis-specific proteasome subunit α4s/PSMA8 is essential for male fertility by promoting proper formation of spermatoproteasomes, which harbor both PA200 and constitutive catalytic subunits. Immunostaining of a spermatocyte marker, SYCP3, indicated that meiosis was halted at the stage of spermatocytes in the α4s-deficient testes. α4s stimulated the in vitro degradation of the acetylated core histones, instead of nonacetylated histones, by the PA200-proteasome. Deletion of α4s blocked degradation of the core histones at DNA damage loci in spermatocytes, leading to meiotic arrest at metaphase I. Thus, α4s is required for histone degradation at meiotic DNA damage loci, proper progression of meiosis, and fertility in males by promoting proper formation of spermatoproteasomes. These results are important for understanding male infertility and might provide potential targets for male contraception or treatment of male infertility.

Clinical and Imaging Indicators of Hemorrhagic Transformation in Acute Ischemic Stroke After Endovascular Thrombectomy.

BACKGROUND: Prior studies have investigated the clinical and imaging factors for hemorrhagic transformation (HT), especially symptomatic intracranial hemorrhage (sICH); however, whether alteplase increases the risk of HT after endovascular thrombectomy (EVT) is unknown. This study aimed to assess clinical and imaging features associated with HT, sICH, and parenchymal hematoma (PH) in patients with acute ischemic stroke after EVT, with and without intravenous alteplase in DIRECT-MT (Direct Intraarterial Thrombectomy to Revascularize Acute Ischemic Stroke Patients with Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals: a Multicenter Randomized Clinical Trial). METHODS: The DIRECT-MT trial is a randomized trial of EVT alone versus intravenous thrombolysis combined with EVT. HT, sICH, and PH was evaluated on follow-up computed tomography. Multivariable ordinal logistic regression analysis was used to test the association of stepwise selected determinants with HT, sICH, and PH. RESULTS: In total, 633 patients were analyzed; 261 (41.2%) had HT; 34 (5.4%) had sICH; and 85 (13.4%) had PH. The median age was 69, and 56.7% were men. The median National Institutes of Health Stroke Scale score was 18, and 320 patients were in combination-therapy group. Symptomatic intracranial hemorrhage was associated with higher baseline National Institutes of Health Stroke Scale score (adjusted odds ratio [OR], 1.06 [95% CI, 1.10-1.12]) and higher glucose level at hospital arrival (adjusted OR, 1.14 [95% CI, 1.00-1.29]). No association was found between alteplase treatment and HT, sICH, or PH. The independent predictor of sICH was higher baseline National Institutes of Health Stroke Scale score (adjusted OR, 1.09 [95% CI, 1.01-1.18]) in EVT alone group, and history of anticoagulant drugs (adjusted OR, 3.75 [95% CI, 1.07-13.06]), higher glucose level at hospital arrival (adjusted OR, 1.19 [95% CI, 1.03-1.38]), >3 passes of device (adjusted OR, 4.42 [95% CI, 1.36-14.32]) in combination-therapy group. CONCLUSIONS: In DIRECT-MT, independent predictors of sICH were baseline National Institutes of Health Stroke Scale score and glucose level at hospital arrival. Alteplase treatment did not increase the risk of HT, sICH, or PH after EVT. The independent predictor of sICH was different in EVT alone group and combination-therapy group. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03469206.

Use of medical exome sequencing for identification of underlying genetic defects in NICU: Experience in a cohort of 2303 neonates in China.

Emerging evidence demonstrates the clinical utility of genomic applications in newborn intensive care unit (NICU) patients with strong indications of Mendelian etiology. However, such applications' diagnostic yield and utility remain unclear for NICU cohorts with minimal phenotype selection. In this study, focused medical exome sequencing was used as a first-tier, singleton-focused diagnostic tool for 2303 unrelated sick neonates. Integrated analysis of single nucleotide variants (SNVs), small insertions and deletions (Indels), and large copy number variants (CNVs) was performed. The diagnostic rate in this NICU cohort is 12.3% (284/2303), with 190 probands with molecular diagnoses made from SNV/Indel analyses (66.9%), 93 patients with diagnostic aneuploidy/CNVs findings (32.8%), and 1 patient with both SNV and CNV (0.4%). In addition, 54 (2.3%) of patients had a reportable incidental finding. Multiple organ involvements, craniofacial abnormalities, and dermatologic abnormalities were the strongest positive predictors for a molecular diagnosis. Among the 190 cases with SNV/Indel defects, direct impacts on medical management were observed in 46.8% of patients after the results were reported. In this study, we demonstrate that focused medical exome sequencing is a powerful first-line diagnostic tool for NICU patients. Significant number of diagnosed NICU patients can benefit from more focused medical management and long-term care.

A deep learning-based system for real-time image reporting during esophagogastroduodenoscopy: a multicenter study.

BACKGROUND AND STUDY AIMS: Endoscopic reports are essential for the diagnosis and follow-up of gastrointestinal diseases. This study aimed to construct an intelligent system for automatic photo documentation during esophagogastroduodenoscopy (EGD) and test its utility in clinical practice. PATIENTS AND METHODS: Seven convolutional neural networks trained and tested using 210,198 images were integrated to construct the endoscopic automatic image reporting system (EAIRS). We tested its performance through man-machine comparison at three levels: internal, external, and prospective test. Between May 2021 and June 2021, patients undergoing EGD at Renmin Hospital of Wuhan University were recruited. The primary outcomes were accuracy for capturing anatomical landmarks, completeness for capturing anatomical landmarks, and detected lesions. RESULTS: The EAIRS outperformed endoscopists in retrospective internal and external test. A total of 161 consecutive patients were enrolled in the prospective test. The EAIRS achieved an accuracy of 95.2% in capturing anatomical landmarks in the prospective test. It also achieved higher completeness on capturing anatomical landmarks compared with endoscopists: (93.1% vs. 88.8%), and was comparable to endoscopists on capturing detected lesions: (99.0% vs. 98.0%). CONCLUSIONS: The EAIRS can generate qualified image reports and could be a powerful tool for generating endoscopic reports in clinical practice.