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Type III effectors (T3Es) are major determinants of Xanthomonas virulence and targets for resistance breeding. XopJ2 (synonym AvrBsT) is a highly conserved YopJ-family T3E acquired by X. perforans, the pathogen responsible for bacterial spot disease of tomato. In this study, we characterized a new variant (XopJ2b) of XopJ2, which is predicted to have a similar three-dimensional (3D) structure as the canonical XopJ2 (XopJ2a) despite sharing only 70% sequence identity. XopJ2b carries an acetyltransferase domain and the critical residues required for its activity, and the positions of these residues are predicted to be conserved in the 3D structure of the proteins. We demonstrated that XopJ2b is a functional T3E and triggers a hypersensitive response (HR) when translocated into pepper cells. Like XopJ2a, XopJ2b triggers HR in Arabidopsis that is suppressed by the deacetylase, SOBER1. We found xopJ2b in genome sequences of X. euvesicatoria, X. citri, X. guizotiae, and X. vasicola strains, suggesting widespread horizontal transfer. In X. perforans, xopJ2b was present in strains collected in North America, Africa, Asia, Australia, and Europe, whereas xopJ2a had a narrower geographic distribution. This study expands the Xanthomonas T3E repertoire, demonstrates functional conservation in T3E evolution, and further supports the importance of XopJ2 in X. perforans fitness on tomato. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Background Improving the quality of medical care in hospitals is a major priority for all departments. The early warning score (EWS) trend is an effective early risk stratification tool that reflects the changes in patient condition and allows better assessment of deterioration risk. Objective The aim of this study was to investigate whether utilizing the trend of the modified early warning score (MEWS) level within 4 h of a patient's arrival in the emergency department (ED) could identify patients at risk of clinical deterioration at 8 h after arrival in the ED. Methods We conducted a retrospective observational study of non‐trauma patients who had at least two vital sign measurements (Glasgow Coma Scale score, heart rate, blood pressure, respiratory rate, and body temperature) within 8 h of arriving in the ED. The primary outcome was patients who had MEWS ≥ 4 at 8 h after arrival in the ED. We performed multivariate logistic regression analysis using age, sex, MEWS level at arrival in the ED, MEWS level within 4 h after arrival in the ED, and MEWS level trend over time. Results Among the 5825 patients, 680 (11.7%) were at risk of deterioration at 8 h after arrival in the ED. To predict the risk of deteriorating conditions (MEWS ≥ 4), utilizing the MEWS level trend within 4 h of arrival in the ED was more effective in identifying patients at risk of deterioration after 8 h of arrival in the ED compared to using a single MEWS value during the ED stay. The corresponding areas under the receiver operating characteristic curve were 0.756 (95% confidence interval (CI) 0.734–0.778) and 0.846 (95% CI 0.827–0.865), respectively (p

Background/purpose: Oral submucous fibrosis (OSF), characterized by excessive collagen deposition by myofibroblasts, is often linked to Areca nuts consumption. Probiotics consumption has shown protective effects against fibrotic diseases, and recently, their metabolic byproducts, known as postbiotics, have demonstrated superior advantages over probiotics. However, studies on the therapeutic impact of postbiotics on OSF have been scarce. Therefore, this study aims to examine the effect of PostBio GK4, a postbiotic derived from Lactobacillus pentosus GK4, on OSF and explore its underlying mechanisms. Materials and methods: The cytotoxicity of GK4 in normal buccal mucosal fibroblasts (BMFs) and fibrotic BMFs (fBMFs) were assessed. Following this, we evaluated the effects of GK4 on collagen contraction, migratory, and wound healing capacities in arecoline-induced fibrotic BMFs. Next, Western blotting and ELISA were employed to assess GK4's impact on fibrosis-related proteins such as COL1A1, and α-SMA, as well as on TGF-β and Smad2/3 signaling pathway. Results: Arecoline was shown to stimulate cell migratory, contractile and wound healing abilities as well as the expression of α-SMA and COL1A1 in BMFs. Treatment with GK4 reduced all arecoline-induced phenomena in BMFs. Moreover, GK4 diminished the increased expression of TGF-β and Smad2/3. Conclusion: Our findings proposed that GK4 may exert a suppressive effect on arecoline-induced myofibroblast activities via the inhibition of TGF-β and Smad2/3 signaling pathway. Therefore, GK4 holds promise as an adjunct therapeutic approach for intervening in OSF. Further in-vivo and clinical studies are warranted to validate these observations.

Most speakers' first language (L1) in Hong Kong and Guangdong China is Cantonese. Even though the L1 of both Guangdong Cantonese speakers and Hong Kong Cantonese speakers is the same, their second languages (L2) belong to different language families. Previous studies have pointed out that L2 status in third language (L3) acquisition is a salient factor. This study aimed to: (1) examine Guangdong Cantonese speakers' pronunciation error patterns in their L2 Mandarin and L3 English and explore the language interaction patterns among these three languages; (2) compare the findings with those of Hong Kong Cantonese speakers whose L2 is English and L3 Mandarin in Chen and Han (2019. L3 phonology: contributions of L1 and L2 to L3 pronunciation learning by Hong Kong speakers. International Journal of Multilingualism, 16(4), 492-512. https://doi.org/10.1080/14790718.2019.1573901) to identify the roles of L1 and L2 in L3 acquisition. Results of the reading aloud tasks, a questionnaire survey and interview data show that the language interaction patterns among L1, L2 and L3 are influenced by learners' language proficiency.

Abstract We present an in‐depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low‐density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence‐based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.

Abstract Background There are several surgical options for osteonecrosis of the lunate, and confirming the effectiveness of various surgical methods remains challenging. Here, we present a case of stage IIIB osteonecrosis of the lunate repaired with a free medial femoral condyle osteocutaneous flap. Case presentation A 43-year-old male construction worker was admitted to our hospital due to right wrist pain, impaired mobility, and pain aggravated by activity for 10 months. The patient was diagnosed with stage IIIB osteonecrosis of the lunate based on the orthopantomogram and magnetic resonance imaging of the right wrist. Considering the patient’s medical history, physical examination, auxiliary examination, and wishes, reconstruction was performed using a free medial femoral condyle osteocutaneous flap. After the flap survived completely, the K-wires were removed one month after the operation, the external brace was removed two months after the operation, and functional wrist rehabilitation was initiated. After six months of follow-up, the wrist swelling and pain resolved, and the reconstructed lunate bone was viable. Additionally, the last follow-up was conducted in the sixth month after surgery; the affected hand grip strength improved from about 70% (28 kg) to 80% (32 kg) compared with the healthy side (40 kg); the visual analog scale score decreased from 6.5 points before the operation to 1 point; and the MAYO score increased from 60 points before the operation to 85 points. Conclusions The success of this case reinforces the potential of the free medial femoral condyle osteocutaneous flap as a new treatment option for stage IIIB osteonecrosis of the lunate and further expands the existing treatment options. Using a free medial femoral condyle osteocutaneous flap to reconstruct the lunate and restore the carpal anatomy may.

Abstract Secretory cells in the fallopian tube fimbria epithelium (FTE) are regarded as the main cells of origin of ovarian high-grade serous carcinoma (HGSC). Ovulation is the main cause of FTE oncogenesis, which proceeds through a sequence of TP53 mutations, chromosomal instability due to Rb/cyclin E aberration, in situ carcinoma (STIC), and metastasis to the ovary and peritoneum (metastatic HGSC). Previously, we have identified multiple oncogenic activities of the ovulatory follicular fluid (FF), which exerts the full spectrum of transforming activity on FTE cells at different stages of transformation. After ovulation, the FF is transfused into the peritoneal fluid (PF), in which the FTE constantly bathes. We wondered whether PF exerts the same spectrum of oncogenic activities as done by FF and whether these activities are derived from FF. By using a panel of FTE cell lines with p53 mutation (FT282-V), p53/CCNE1 aberrations (FT282-CCNE1), and p53/Rb aberrations plus spontaneous transformation, and peritoneal metastasis (FEXT2), we analyzed the changes of different transformation phenotypes after treating with FF and PF collected before or after ovulation. Similar to effects exhibited by FF, we found that, to a lesser extent, PF promoted anchorage-independent growth (AIG), migration, anoikis resistance, and peritoneal attachment in transforming FTE cells. The more transformed cells were typically more affected. Among the transforming activities exhibited by PF treatment, AIG, Matrigel invasion, and peritoneal attachment growth were higher with luteal-phase PF treatment than with the proliferative-phase PF treatment, suggesting an ovulation source. In contrast, changes in anoikis resistance and migration activities were similar in response to treatment with PF collected before and after ovulation, suggesting an ovulation-independent source. The overall transforming activity of luteal-phase PF was verified in an i.p. co-injection xenograft mouse model. Co-injection of Luc-FEXT2 cells with either FF or luteal-phase PF supported early peritoneal implantation, whereas co-injection with follicular-phase PF did not. This study, for the first time, demonstrates that PF from ovulating women can promote different oncogenic phenotypes in FTE cells at different stages of malignant transformation. Most of these activities, other than anoikis resistance and cell migration, are sourced from ovulation.

Elastomeric polymer materials are of interest due to their stretchability, low‐temperature processing, and scalability. In addition, the incorporation of 2D materials can further enhance the dielectric properties and capacitance of elastic polymer materials, thereby reducing the driving voltage and energy consumption. In this study, titanium dioxide (TiO2) nanosheets are cross‐linked with nitrile butadiene rubber using thiol‐ene click chemistry, which leads to the preparation of nanocomposite dielectric films with stretchability and high dielectric constant. Furthermore, by controlling the doping amount of the nanosheets, it is observed that the capacitance of the nanocomposite films increases from 25.61 to 684.67 nF cm−2, and the dielectric constant increases from 14.96 to 161.98. Finally, the stretchable nanocomposite films exhibit good insulating properties even at 50% strain. In this study, insight is provided into the potential of in situ cross‐linking between elastic polymer materials and 2D materials to produce high‐k dielectric materials with both stretchability and high insulating properties.

Erinacine A has been proven to have the ability to protect nerves and have the benefit of neurohealth. However, the pharmacokinetic and metabolites study of erinacine A in pigs, whose physiology and anatomy are similar to humans, have not been reported. In this study, 5 mg/kg of erinacine A was intravenously administered to the landrace pig. Blood, cerebrospinal fluid, and brain tissue samples were collected and analyzed by HPLC-QQQ/MS and UPLC-QTOF/MS. The results indicated the following pharmacokinetic parameters in plasma samples: with an area under the plasma concentration versus time curve (AUC) were 38.02 ± 0.03 mg∙min/L (AUC0-60) and 43.60 ± 0.06 mg∙min/L (AUC0-∞), clearance (CL) was 0.11 ± 0.00 L/min∙kg, volume of distribution (Vd) was 4.24 ± 0.00 L/kg, and terminal half-life (T1/2β) was 20.85 ± 0.03 min. In the cerebrospinal fluid samples, erinacine A was detected after 15 min and the highest concentration (5.26 ± 0.58 μg/L) was observed at 30 min. In the brain tissue sample, 77.45 ± 0.58 μg/L of erinacine A was found. In the study of metabolites, there were 6 identical metabolites in plasma and brain tissue. To our surprise, erinacine B was found to be the metabolite of erinacine A, and its concentration increased over time as erinacine A was metabolized. In summary, this study is the first to demonstrate that erinacine A can be found in the cerebrospinal fluid of landrace pigs. Additionally, the metabolite identification of erinacine A in landrace pigs is also investigated.

Abstract Background The hospitalization rate of ambulatory care sensitive conditions (ACSCs) has been recognized as an essential indicator reflective of the overall performance of healthcare system. At present, ACSCs has been widely used in practice and research to evaluate health service quality and efficiency worldwide. The definition of ACSCs varies across countries due to different challenges posed on healthcare systems. However, China does not have its own list of ACSCs. The study aims to develop a list to meet health system monitoring, reporting and evaluation needs in China. Methods To develop the list, we will combine the best methodological evidence available with real-world evidence, adopt a systematic and rigorous process and absorb multidisciplinary expertise. Specific steps include: (1) establishment of working groups; (2) generations of the initial list (review of already published lists, semi-structured interviews, calculations of hospitalization rate); (3) optimization of the list (evidence evaluation, Delphi consensus survey); and (4) approval of a final version of China’s ACSCs list. Within each step of the process, we will calculate frequencies and proportions, use descriptive analysis to summarize and draw conclusions, discuss the results, draft a report, and refine the list. Discussion Once completed, China’s list of ACSCs can be used to comprehensively evaluate the current situation and performance of health services, identify flaws and deficiencies embedded in the healthcare system to provide evidence-based implications to inform decision-makings towards the optimization of China’s healthcare system. The experiences might be broadly applicable and serve the purpose of being a prime example for nations with similar conditions.

The development of biomass-based solid polymer electrolytes (SPEs) as a desirable alternative to traditional organic liquid electrolytes and separators is crucial to advancing sustainable, safer, and high-performance lithium batteries. Biomass is a natural polymer with the advantages of biodegradability, low cost, and abundant availability. However, low ionic conductivity remains a major drawback limiting its commercial applications. Therefore, many literatures have reported the enhancement of ionic conductivity and mechanical stability of SPEs by chemically modifying biomass with various functional groups and composite structures. This review summarizes the structural features, physicochemical properties and different types of biomass derivatives, as well as recent advances in the field of biomass-based SPEs. Finally, we propose an outlook on the future development of cellulose-based SPEs for lithium metal batteries (LMBs).

Summary: Postoperative adhesions show a higher occurrence in females aged 16–60, especially after pelvic surgeries. This study explores the role of ovulation in adhesion formation in mice. Ovarian surgery in mice with normal- or super-ovulation led to pronounced adhesions, whereas ovulation-defective Pgr-KO mice showed minimal adhesions. Specifically, exposure to ovulatory follicular fluid (FF) markedly increased the adhesion. The hazardous exposure time window was one day before to 2.5 days after the surgery. Mechanistically, early FF exposure triggered adhesions via the blood coagulation cascade, while later exposure relied on the HGF/cMET signaling pathway. Prophylactic administration of a thrombin inhibitor pre-operatively or a cMET inhibitor postoperatively effectively mitigated FF-induced adhesions, while COX inhibitor treatment exhibited no discernible effect. These findings underscore ovulation as a pivotal factor in the development of pelvic wound adhesions and advocate for targeted preventive strategies such as c-MET inhibition, scheduling surgeries outside the ovulatory period, or employing oral contraceptive measures.

Introduction: Intra-arrest transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have been introduced in adult patients with cardiac arrest (CA). Whether the diagnostic performance of TTE or TEE is superior during resuscitation is unclear. We conducted a systematic review following PRISMA guidelines. Methods: We searched databases from PubMed, Embase, and Google Scholar and evaluated articles with intra-arrest TTE and TEE in adult patients with non-traumatic CA. Two authors independently screened and selected articles for inclusion; they then dual-extracted study characteristics and target conditions (pericardial effusion, aortic dissection, pulmonary embolism, myocardial infarction, hypovolemia, left ventricular dysfunction, and sonographic cardiac activity). We performed quality assessment using the Quality Assessment of Diagnostic Accuracy Studies Version 2 criteria. Results: A total of 27 studies were included: 14 studies with 2,145 patients assessed TTE; and 16 with 556 patients assessed TEE. A high risk of bias or applicability concerns in at least one domain was present in 20 studies (74%). Both TTE and TEE found positive findings in nearly one-half of the patients. The etiology of CA was identified in 13% (271/2,145), and intervention was performed in 38% (102/271) of patients in the TTE group. In patients who received TEE, the etiology was identified in 43% (239/556), and intervention was performed in 28% (68/239). In the TEE group, a higher incidence regarding the etiology of CA was observed, particularly for those with aortic dissection. However, the outcome of those with aortic dissection in the TEE group was poor. Conclusion: While TEE could identify more causes of CA than TTE, sonographic cardiac activity was reported much more in the TTE group. The impact of TTE and TEE on the return of spontaneous circulation and further survival was still inconclusive in the current dataset.

Abstract Background Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored. Methods Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the International Lung Cancer Consortium. Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean/PRS CI and the population level threshold. Results Considerable variances in PRS point estimates at the individual level were observed for both methods, with an average standard deviation (s.d.) of 0.12 for PRS-16-CV and a much larger s.d. of 0.88 for PRS-Bayes. Using PRS-16-CV, only 25.0% of individuals with PRS point estimates in the lowest decile of PRS and 16.8% in the highest decile have their entire 95% CI fully contained in the lowest and highest decile, respectively, while PRS-Bayes was unable to find any eligible individuals. Only 19% of the individuals were concordantly identified as having high genetic risk (> 90th percentile) using the two PRS estimators. An increased relative risk of lung cancer comparing the highest PRS percentile to the lowest was observed when taking the CI into account (OR = 2.73, 95% CI: 2.12–3.50, P-value = 4.13 × 10−15) compared to using PRS-16-CV mean (OR = 2.23, 95% CI: 1.99–2.49, P-value = 5.70 × 10−46). Improved risk prediction performance with higher AUC was consistently observed in individuals identified by PRS-16-CV CI, and the best performance was achieved by incorporating age, gender, and detailed smoking pack-years (AUC: 0.73, 95% CI = 0.72–0.74). Conclusions Lung cancer PRS estimates using different methods have modest correlations at the individual level, highlighting the importance of considering individual-level uncertainty when evaluating the practical utility of PRS.

Abstract Background The residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event. Methods Data on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/ ) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined. Results The 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log–alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure. Conclusion This study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

Given the increasing use of cannabis in the US, there is an urgent need to better understand the drug’s effects on central signaling mechanisms. Extracellular vesicles (EVs) have been identified as intercellular signaling mediators that contain a variety of cargo, including proteins. Here, we examined whether the main psychoactive component in cannabis, Δ9-tetrahydrocannabinol (THC), alters EV protein signaling dynamics in the brain. We first conducted in vitro studies, which found that THC activates signaling in choroid plexus epithelial cells, resulting in transcriptional upregulation of the cannabinoid 1 receptor and immediate early gene c-fos, in addition to the release of EVs containing RNA cargo. Next, male and female rats were examined for the effects of either acute or chronic exposure to aerosolized (‘vaped’) THC on circulating brain EVs. Cerebrospinal fluid was extracted from the brain, and EVs were isolated and processed with label-free quantitative proteomic analyses via high-resolution tandem mass spectrometry. Interestingly, circulating EV-localized proteins were differentially expressed based on acute or chronic THC exposure in a sex-specific manner. Taken together, these findings reveal that THC acts in the brain to modulate circulating EV signaling, thereby providing a novel understanding of how exogenous factors can regulate intercellular communication in the brain.

Early development is characterized by dynamic transitions in brain maturation, which may be impacted by environmental factors. Here, we sought to determine the effects of social isolation from postweaning and during adolescence on reward behavior and dopaminergic signaling in male rats. Subjects were socially isolated or group housed at postnatal day 21. Three weeks later, extracellular dopamine concentrations were examined in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (NAc) during a feeding bout. Surprisingly, opposing effects were found in which increased mPFC dopamine concentrations were observed in group housed, but not isolated, rats. In stark contrast, increased dopamine levels were found in the NAc of isolated, but not group housed, rats. Moreover, the absence of an effect in the mPFC of the isolated rats could not be reversed by subsequent group housing, demonstrating the remarkable long-term effects on dopamine signaling dynamics. When provided a highly palatable food, the isolated subjects exhibited a dramatic increase in mPFC dopamine levels when the chocolate was novel, but no effects following chronic chocolate consumption. In contrast, the group housed subjects showed significantly increased dopamine levels only with chronic chocolate consumption. The dopamine changes were correlated with differences in behavioral measures. Importantly, the deficit in reward-related behavior during isolation could be reversed by microinjection of either dopamine or cocaine into the mPFC. Together, these data provide evidence that social isolation from postweaning and during adolescence alters reward-induced dopamine levels in a brain region-specific manner, which has important functional implications for reward-related behavior.