Phase Behaviors and Photoresponsive Thin Films of Syndiotactic Side-Chain Liquid Crystalline Polymers with High Densely Substituted Azobenzene Mesogens.

Azobenzene-containing polymers (azopolymers) are a kind of fascinating stimuli-responsive materials with broad and versatile applications. In this work, a series of syndiotactic C1 type azopolymers of Pm-Azo-Cn with side-chain azobenzene mesogens of varied length alkoxy tails (n = 1, 4, 8, 10) and different length alkyl spacers (m = 6, 10) have been prepared via Rh-catalyzed carbene polymerization. The thermal properties and ordered assembly structures of thus synthesized side chain liquid crystalline polymers (SCLCPs) have been systematically investigated with differential scanning calorimetry (DSC), polarized optical microscopy (POM) and variable-temperature small/wide-angle X-ray scattering (SAXS/WAXS) analyses. P10-Azo-C1 and P10-Azo-C4 with shorter alkoxy tails exhibited hierarchical structures SmB/Colob and transformed into SmA/Colob at a higher temperature, while P10-Azo-C8 and P10-Azo-C10 with longer alkoxy tails only displayed side group dominated layered SmB phase and transformed into SmA phase at higher temperatures. For P6-Azo-C4 with a shorter spacer only showed a less ordered SmA phase owing to interference by partly coupling between the side chain azobenzene mesogens and the helical backbone. More importantly, the series high densely substituted syndiotactic C1 azopolymer thin films, exhibited evidently and smoothly reversible photoresponsive properties, which demonstrated promising photoresponsive device applications.

A scoping review of national policies for child road injury in China.

There has been limited examination of child road injury policies. This study aims to systematically characterize national policies relevant to child road safety in China over the past two decades and identify potential gaps based on the WHO child road safety framework. As a scoping review, this study searched for national policies for child road safety on the websites of government agencies. A total of 22,487 policies were searched, of which 103 policies issued by 37 institutions, were included in the analysis, including 12 policies jointly developed by multiple agencies. Mapping identified policies to strategies in the WHO framework, most WHO strategies requiring legislation were found to be in place in China and to fully meet the intent of the WHO recommendation. The single exception was in the area of child restraints which was deemed to not be fully covered due to a lack of eligible policies on enforcement of child restraint use laws. Two strategies requiring standards were fully covered; eight strategies requiring policy support were partially or not covered, mainly related to equipping emergency vehicles with child-appropriate medical equipment. Enhancing school bus safety was identified as a policy focus area in China beyond those recommended by the WHO framework. This study identified three areas for improvement: (1) strengthening road safety policies targeting children, (2) strengthening enforcement of legislation, e.g., child restraint use, and (3) increasing multiple-sector cooperation on policy formulation. Funding: Ye Jin is supported by the Scholarship from the George Institute for Global Health and Tuition Fee Scholarships from University of New South Wales.

Adaptive attenuation of virulence in hypervirulent carbapenem-resistant Klebsiella pneumoniae.

The emergence of nosocomial infections caused by hypervirulent and carbapenem-resistant K. pneumoniae (hv-CRKP) has become a significant public health challenge. The genetic traits of virulence and resistance plasmids in hv-CRKP have been extensively studied; however, research on the adaptive evolution strategies of clinical strains inside the host was scarce. This study aimed to understand the effects of antibiotic treatment on the phenotype and genotype characteristics of hv-CRKP. We investigated the evolution of hv-CRKP strains isolated from the same patient to elucidate the transition between hospital invasion and colonization. A comparative genomics analysis was performed to identify single nucleotide polymorphisms in the rmpA promoter. Subsequent validation through RNA-seq and gene deletion confirmed that distinct rmpA promoter sequences exert control over the mucoid phenotype. Additionally, biofilm experiments, cell adhesion assays, and animal infection models were conducted to illuminate the influence of rmpA promoter diversity on virulence changes. We demonstrated that the P12T and P11T promoters of rmpA possess strong activity, which leads to the evolution of CRKP into infectious and virulent strains. Meanwhile, the specific sequence of polyT motifs in the rmpA promoter led to a decrease in the lethality of hv-CRKP and enhanced cell adhesion and colonization. To summarize, the rmpA promoter of hv-CRKP is utilized to control capsule production, thereby modifying pathogenicity to better suit the host's ecological environment.IMPORTANCEThe prevalence of hospital-acquired illness caused by hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) is significant, leading to prolonged antibiotic treatment. However, there are few reports on the phenotypic changes of hv-CRKP in patients undergoing antibiotic treatment. We performed a comprehensive examination of the genetic evolutionary traits of hv-CRKP obtained from the same patient and observed variations in the promoter sequences of the virulence factor rmpA. The strong activity of the promoter sequences P11T and P12T enhances the consistent production of capsule polysaccharides, resulting in an invasive strain. Conversely, weak promoter activity of P9T and P10T is advantageous for exposing pili, hence improving bacterial cell attachment ability and facilitating bacterial colonization. This finding also explains the confusion of some clinical strains carrying wild-type rmpA but exhibiting a low mucoid phenotype. This adaptive alteration facilitates the dissemination of K. pneumoniae within the hospital setting.

Changes associated with the COVID-19 pandemic on postpartum screening results in Ontario, Canada: The healthy babies healthy children screening tool.

BACKGROUND: Research on the impact of the COVID-19 pandemic on mothers/childbearing parents has mainly been cross-sectional and focused on psychological symptoms. This study examined the impact on function using ongoing, systematic screening of a representative Ontario sample. METHODS: An interrupted time series analysis of repeated cross-sectional data from a province-wide screening program using the Healthy Babies Healthy Children (HBHC) tool assessed changes associated with the pandemic at the time of postpartum discharge from hospital. Postal codes were used to link to neighborhood-level data. The ability to parent or care for the baby/child and other psychosocial and behavioral outcomes were assessed. RESULTS: The co-primary outcomes of inability to parent or care for the baby/child were infrequently observed in the pre-pandemic (March 9, 2019-March 15, 2020) and initial pandemic periods (March 16, 2020-March 23, 2021) (parent 209/63,006 (0.33%)-177/56,117 (0.32%), care 537/62,955 (0.85%)-324/56,086 (0.58%)). Changes after pandemic onset were not observed for either outcome although a significant (p = 0.02) increase in slope was observed for inability to parent (with questionable clinical significance). For secondary outcomes, worsening was only seen for reported complications during labor/delivery. Significant improvements were observed in the likelihood of being unable to identify a support person to assist with care, need of newcomer support, and concerns about money over time. CONCLUSIONS: There were no substantive changes in concerns about ability to parent or care for children. Adverse impacts of the pandemic may have been mitigated by accommodations for remote work and social safety net policies.

Heatwaves increase road traffic injury morbidity risk and burden in China and its provinces.

Previous studies have demonstrated health impacts of climate change, but evidence on heatwaves' associations with road traffic injury (RTI) is limited. In this study, individual information of RTI cases in May-September during 2006-2021 in China were obtained from the National Injury Surveillance System. Daily maximum temperatures (TMmax) during 2006-2021 were collected from the ERA-5 reanalysis, and the projected daily TMmax during 2020-2099 were obtained from the latest Coupled Model Intercomparison Project Phase 6 Shared Socioeconomic Pathways scenarios (SSPs). We used a time-stratified case-crossover analysis to investigate the association between short-term exposure (lag01 days) to heatwaves (exceeding the 92.5th percentile of daily TMmax for ≥ three consecutive days) and RTI, and to project heatwave-related RTI until 2099 across China. Finally, a total of 1 031 082 RTI cases were included in the analyses. Compared with non-heatwaves, the risks of RTI increased by 3.61 % during heatwaves. Greater associations were found in people aged 15-64 years, in people with transportation occupation, for non-motor traffic vehicle injuries, for severe RTI cases, and in Western China particularly in Qinghai province. We projected substantial increases in attributable fraction (AF) of heatwave-related RTI in the future, particularly in Western and Southwest China. The national average increase in AF (per decade) during 2020s-2090s was 0.036 % for SSP1-2.6 scenario, and 0.267 % for SSP5-8.5 scenario. This study provided evidence on the associations of heatwaves with RTI, and the heatwave-related RTI will substantially increase in the future.

Ruthenium-Catalyzed Difunctionalization of Vinyl Cyclopropanes for Double m-C(sp2)-H/C-5(sp3)-H Functionalization.

With in-depth research on 1,2-difunctionalization, remote difunctionalization has garnered widespread attention for achieving multifunctionality. Herein, we report a strategy for achieving remote difunctionalization under mild conditions. This strategy exhibited good substrate suitability and functional group tolerance. In addition, the significance of this method is further evidenced by its successful application in scaling up and conducting additional transformations of target compounds. Mechanistic studies showed that a radical might be involved in this process.

Can We Differentiate Between Primary Sjögren Syndrome and Idiopathic Multicentric Castleman Disease Based on the Characteristics of Pulmonary Cysts?

PURPOSE: To identify radiological characteristics that could help differentiate cystic lung diseases between primary Sjögren syndrome (pSS) and idiopathic multicentric Castleman disease (iMCD). PATIENTS AND METHODS: Patients with pSS or iMCD who had cysts were enrolled. Cyst characteristics (number, size, morphology, and distribution) and other accompanying manifestations (nodules, ground-glass opacities, calcification, and thickening of the bronchovascular bundles and interlobular septa) were compared between them. RESULTS: Eleven patients with pSS and 25 patients with iMCD were eligible for our study. Eleven patients with pSS (100.0%) and 23 patients with iMCD (92.0%) had round or oval cysts. None of the patients with pSS had irregular cysts, but 21 (84.0%) patients with iMCD had irregular cysts (P = 0.005). Smooth-walled cysts were present in 11 patients with pSS (100.0%) and 18 patients with iMCD (72.0%). Only 1 patient with pSS (9.1%) exhibited non-smooth-walled cysts, whereas 23 patients with iMCD (92.0%) had non-smooth-walled cysts (P = 0.003). The presence of nodules was common in both groups (P = 1.000). However, the nodules were more likely to be larger and more numerous in patients with iMCD (P < 0.001). Cysts with mural nodules (52.2%) and central nodules (47.8%) were only observed in iMCD (P = 0.007). CONCLUSION: Although regular and smooth-walled cysts were common in the 2 diseases, irregular and non-smooth-walled cysts were more often associated with iMCD than pSS. Nodules in iMCD tended to be larger and more numerous, and a close positional relationship between nodules and cysts was only observed in iMCD.

Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

Associations of ambient temperature with the CO poisoning risk in China.

Although studies have explored the relationship between temperature and CO poisoning, the results are not consistent, and there is still a lack of early warning criteria of temperature related to CO poisoning. In order to comprehensively study the exposure-response relationship between daily average temperature and CO poisoning, and to further explore the early warning criteria of temperature related to CO poisoning, we used daily cases of CO poisoning in 31 National Injury Surveillance System (NISS) surveillance sites in seven administrative geographical regions of China and daily meteorological data obtained from the China Meteorological Science Data Sharing Service Platform from 2009 to 2019 to do the analysis. Daily meteorological data of 698 weather stations across China were interpolated at a 0.01° × 0.01°spatial resolution, which were then applied to extract the daily meteorological data of all included NISS sites. The Distributed Lag Non-linear Model (DLNM) model was applied to estimate the exposure-response associations (relative risk, RR) of daily mean temperature with CO poisoning, which was then further used to identify early warning criteria of temperature related to CO poisoning. A total of 10,618 CO poisoning cases were included in this study, with an average of 0.4 cases per day. There was generally a reverse J-shaped association between temperature and CO poisoning risk, indicating that both low and high temperature may increase the risk of CO poisoning, but low temperature usually has a longer lagged effects than high temperature. Spatialy, the exposure-response associations between temperatue and CO poisoning largely varied among regions, with greater effects of low temperatures in Southern China than in Northern China. The cumulative effects (RR, lag0-6 days) of 10 % percentile temperature ranged from 1.13 (95%CI: 1.01,1.26) in East China to 1.73 (95%CI:1.63,1.83) in South China. We also observed significant spatial variations in the early warning criteria of temperature related to CO poisoning across China. However, the patterns of high temperature effects on CO poisoning and the warning criteria of high temperature were mixed across China. In conclusions, both low temperature and high temperature may increase the risk of CO poisoning in China, and the effect of low temperature is more obvious, especially in South China, Northeast China, and North China. In addition, there is an urgent need to establish air temperature early warning and grading criteria for CO poisoning in different areas of China.

Continuous and controllable synthesis of MnO2 adsorbents for H2S removal at low temperature.

H2S is an extremely noxious impurity generated from nature and chemical industrial processes. High performing H2S adsorbents are required for chemical industry and environmental engineering. Herein, α-, γ-, and δ-MnO2 adsorbents with high sulfur capacity were synthesized through a continuous-flow approach with a microreactor system, achieving much higher efficiency than hydrothermal methods. The relationship between crystal structure and synthesis conditions such as residence time, reaction temperature, concentration of K+ in solution and reactant ratio is discussed. According to the H2S breakthrough tests at 150 °C, continuously prepared α-, γ-, and δ-MnO2 exhibited sulfur capacities of 669.5, 193.8 and 607.6 mg S/g sorbent, respectively, which was at a high level among the reported adsorbents. Such enhanced performance is related to the large surface area and mesopore volume, high reducibility, and a large number of oxygen species with high reactivity and mobility. Manganese sulfide and elemental sulfur were formed after desulfurization, which indicated the reaction consisted of two steps: redox and sulfidation of the sorbents. This study provides an innovative design strategy for the construction of nanomaterials with high H2S adsorption performances.

Association study of FLT4 and HYDIN single nucleotide polymorphisms with atrial septal defect susceptibility in the Han Chinese population of Southwest China.

BACKGROUND: Atrial septal defect (ASD) is a common form of congenital heart disease. Although several genes related to ASD have been found, the genetic factors of ASD remain unclear. This study aimed to evaluate the correlation between 10 candidate single nucleotide polymorphisms (SNPs) and sporadic atrial septal defects. METHODS: Based on the results of 34 individual whole exome sequences, 10 candidate SNPs were selected. In total, 489 ASD samples and 420 normal samples were collected. The 10 SNPs in the case group and the control group were identified through Snapshot genotyping technology. The χ2-test and unconditional regression model were used to evaluate the relationship between ASD and each candidate SNP. Haploview software was used to perform linkage disequilibrium and haplotype analysis. RESULTS: The χ2 results showed that the FLT4 rs383985 (P = 0.003, OR = 1.115-1.773), HYDIN rs7198975 (P = 0.04621, OR = 1.003-1.461), and HYDIN rs1774266 (P = 0.04621, OR = 1.003-1.461) alleles were significantly different between the control group and the case group (P < 0.05). Only the association with the FLT4 polymorphism was statistically significant after adjustment for multiple comparisons. CONCLUSION: These findings suggest that a possible molecular pathogenesis associated with sporadic ASD is worth exploring in future studies.

A mechanics-based model for predicting flexible needle bending with large curvature in soft tissue.

Percutaneous insertion is one of the most common minimally invasive procedures. Compared with traditional straight rigid needles, bevel-tipped flexible needle can generate curved trajectories to avoid obstacles and sensitive organs. However, the nonlinear large deflection problem challenges the bending prediction of the needle, which dramatically influences the surgical success rate. This paper analyzed the mechanism of needle-tissue interaction, and established a mechanics-based model of the needle bending during an insertion. And then, a discretization of the bending model was adopted to accurately predict the large bending of the needle in soft tissue. Insertion experiments were conducted to validate the bending prediction model. The results showed that the large needle bending was predicted with the mean/RMSE/maximumu error of 0.42 mm / 0.26 mm / 1.08 mm, which was clinically acceptable. This proved the rationality and accuracy of the proposed model.

Optical Information Transmission and Multimode Fluorescence Anticounterfeiting of Ca2-xMgxGe7O16:Mn2.

Multimode emission of Mn2+ for multimode fluorescence anticounterfeiting is achieved by cation site and interstitial occupancy in Ca2-xMgxGe7O16. The rings in Ca2-xMgxGe7O16 have a significant distortion for Mn2+ ions to enter the ring interstitials with a luminescence center at 665 nm, which is supported by XRD refinement results and first-principles calculations. The interstitial Mn2+ ion has good thermal stability with an activation energy of 0.36 eV. Surprisingly, these two luminescence centers, the cation site Mn and the interstitial Mn, have an obvious afterglow, and the disappearing afterglow will reappear by heating or irradiating with the 980 nm laser. The afterglow is significantly enhanced, as MnO2 is used as the manganese source, which is explained in detail by the thermal luminescence spectrum. Finally, Ca2-xMgxGe7O16:Mn2+ fully demonstrates its excellent prospects in fluorescent anticounterfeiting, information encryption, and optical information storage.

Effect of sheep bone protein hydrolysate on promoting calcium absorption and enhancing bone quality in low-calcium diet fed rats.

Calcium deficiency is prone to fractures, osteoporosis and other symptoms. In this study, sheep bone protein hydrolysates (SBPHs) were obtained by protease hydrolysis. A low-calcium-diet-induced calcium-deficiency rat model was established to investigate the effects of SBPHs on calcium absorption and intestinal flora composition. The results showed that an SBPHs + CaCl2 treatment significantly increased the bone calcium content, bone mineral density, trabecular bone volume, and trabecular thickness, and reduced trabecular separation, and changed the level of bone turnover markers (P < 0.05). Supplementation of SBPHs + CaCl2 can remarkably enhance the bone mechanical strength, and the microstructure of bone was improved, and the trabecular network was more continuous, complete, and thicker. Additionally, SBPHs + CaCl2 dietary increased the abundance of Firmicutes and reduced the abundance of Proteobacteria and Verrucomicrobiota, and promoted the production of short chain fatty acids. This study indicated that SBPHs promoted calcium absorption and could be applied to alleviate osteoporosis.

Effect of different levels of Lactobacillus added to diets on fat deposition and meat quality of Sunit lambs.

In this study, we examined the impact of adding Lactobacillus to the diet on fat distribution and meat quality of Sunit lambs. For 90 days, twenty-four lambs (19.31 ± 0.47 kg) were fed diets that contained 0 (NP), 6 (P1), 12 (P2), or 24 (P3) g of Lactobacillus casei/d. The results suggested that dietary supplementation with Lactobacillus decreased serum triglyceride in Sunit lambs (P < 0.001). The loin muscle area displayed notable increases in the P1 group (P < 0.05). Meanwhile, tail and visceral fat deposition of lambs were reduced when Lactobacillus was added to the diet (P < 0.05). Compared with the NP group, the values of shear force and cooking loss of in the P1 group exhibited a significant reduction, and intramuscular fat content increased significantly (P < 0.05). Additionally, the P1 group showed an increase in polyunsaturated fatty acids and a decrease in saturated fatty acids in the longissimus thoracis and biceps femoris muscles (P < 0.05). The P1 group showed downregulation of protein kinase AMP-activated catalytic subunit alpha 2 (AMPKα2) and carnitine palmitoyltransferase 1B expression in the longissimus thoracis muscle (P < 0.05). However, there was an upregulation of acetyl-CoA carboxylase (ACC), sterol regulatory element binding transcription factor 1 (SREBF1), and fatty acid synthase (FASN) expression (P < 0.05). In conclusion, feeding Sunit lambs 6 g/d of Lactobacillus as a dietary supplement may be a valuable way to improve fat distribution and meat quality. The AMPK/ACC and AMPK/SREBF1/FASN signaling pathways may be involved in this outcome.

A Nationwide Study on HER2-low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols.

Purpose: Notable effectiveness of trastuzumab deruxtecan (T-DXd) in patients with HER2-low advanced breast cancer (BC) has focused pathologists' attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from twenty-five institutions included in this study. Of these patients, 40.7% (range: 6.0%-76.3%) were classified as HER2-zero, 41.7% (range: 10.5%-69.1%) as HER2-low, and 17.5% (range: 6.7%-34.0%) as HER2-positive. HER2-low tumors were associated with positive ER and PR statuses (p<0.001 and p<0.001, respectively). Antigen retrieval times (≥ 36 min vs. < 36 min) and antibody incubation times (≥ 12 min vs. < 12 min) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy (CNB) and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3259) of the patients. Conclusion: The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Epidemiology and clinical features of Skin and Soft Tissue Infections Caused by PVL-Positive and PVL-Negative Methicillin-Resistant Staphylococcus aureus Isolates in inpatients in China: a single-center retrospective 7-year study.

Previous studies have mainly focused on outpatient cases of skin and soft tissue infections (SSTIs), with limited attention to inpatient occurrences. Thus, we aimed to compare the clinical parameters of inpatients with SSTIs, performed genomic characterization, and determined the subtypes of Panton-Valentine leucocidin (PVL) bacteriophages of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from these patients. We found that PVL-positive patients had shorter hospital stays (mean, 9 vs. 24 days; p < 0.001) and abscess resolution durations (mean, 8 vs. 13 days; p < 0.01). PVL-positive MRSA-induced SSTIs were more frequently associated with abscesses [36/55 (65.5%) vs. 15/124 (12.1%), p < 0.001], with 52.7% undergoing incision and drainage; over 80% of PVL-negative patients received incision, drainage, and antibiotics. In PVL-positive patients receiving empirical antibiotics, anti-staphylococcal agents such as vancomycin and linezolid were administered less frequently (32.7%, 18/55) than in PVL-negative patients (74.2%, 92/124), indicating that patients with PVL-positive SSTIs are more likely to require surgical drainage rather than antimicrobial treatment. We also found that the ST59 lineage was predominant, regardless of PVL status (41.3%, 74/179). Additionally, we investigated the linear structure of the lukSF-PV gene, revealing that major clusters were associated with specific STs, suggesting independent acquisition of PVL by different strain types and indicating that significant diversity was observed even within PVL-positive strains detected in the same facility. Overall, our study provides comprehensive insights into the clinical, genetic, and phage-related aspects of MRSA-induced SSTIs in hospitalized patients and contributes to a more profound understanding of the epidemiology and evolution of these pathogens in the Chinese population.

Phosphorylation of hnRNP A1-Serine 199 Is Not Required for T Cell Differentiation and Function.

hnRNP A1 is an important RNA-binding protein that influences many stages of RNA processing, including transcription, alternative splicing, mRNA nuclear export, and RNA stability. However, the role of hnRNP A1 in immune cells, specifically CD4+ T cells, remains unclear. We previously showed that Akt phosphorylation of hnRNP A1 was dependent on TCR signal strength and was associated with Treg differentiation. To explore the impact of hnRNP A1 phosphorylation by Akt on CD4+ T cell differentiation, our laboratory generated a mutant mouse model, hnRNP A1-S199A (A1-MUT) in which the major Akt phosphorylation site on hnRNP A1 was mutated to alanine using CRISPR Cas9 technology. Immune profiling of A1-MUT mice revealed changes in the numbers of Tregs in the mesenteric lymph node. We found no significant differences in naive CD4+ T cell differentiation into Th1, Th2, Th17, or T regulatory cells (Tregs) in vitro. In vivo, Treg differentiation assays using OTII-A1-Mut CD4+ T cells exposed to OVA food revealed migration and homing defects in the A1-MUT but no change in Treg induction. A1-MUT mice were immunized with NP- keyhole limpet hemocyanin, and normal germinal center development, normal numbers of NP-specific B cells, and no change in Tfh numbers were observed. In conclusion, Akt phosphorylation of hnRNP A1 S199 does not play a role in CD4+ T cell fate or function in the models tested. This hnRNP A1-S199A mouse model should be a valuable tool to study the role of Akt phosphorylation of hnRNP A1-S199 in different cell types or other mouse models of human disease.

Synthesis and Selective Anticancer Activity Evaluation of 2-phenylacrylonitrile Derivatives as Tubulin Inhibitors.

OBJECTIVE: This study aimed at synthesizing 13 series of novel derivatives with 2-phenylacrylonitrile, evaluating antitumor activity both in vivo and in vitro, and obtaining novel tubulin inhibitors. METHOD: The 13 series of 2-phenylacrylonitrile derivatives were synthesized by Knoevenagel condensation and the anti-proliferative activities were determined by MTT assay. The cell cycle and apoptosis were analyzed by flow cytometer. Quantitative cell migration was performed using 24-well Boyden chambers. The proteins were detected by western blotting. in vitro kinetics of microtubule assembly was measured using ELISA kit for Human ß-tubulin (TUBB). Molecular docking was done by Discovery Studio (DS) 2017 Client online tool. RESULTS: Among the derivatives, compound 1g2a possessed strong inhibitory activity against HCT116 (IC50 = 5.9 nM) and BEL-7402 (IC50 = 7.8 nM) cells. Compound 1g2a exhibited better selective antiproliferative activities and specificities than all the positive control drugs, including taxol. Compound 1g2a inhibited proliferation of HCT116 and BEL-7402 cells by arresting them in the G2/M phase of the cell cycle, inhibited the migration of HCT116 and BEL-7402 cells and the formation of cell colonies. Compound 1g2a showed excellent tubulin polymerization inhibitory activity on HCT116 and BEL-7402 cells. The results of molecular docking analyses showed that 1g2a may inhibit tubulin to exert anticancer effects. CONCLUSION: Compound 1g2a shows outstanding antitumor activity both in vivo and in vitro and has the potential to be further developed into a highly effective antitumor agent with little toxicity to normal tissues.

Using a participatory design to develop an implementation framework for integrating falls prevention for older people within the Chinese primary health care system.

BACKGROUND: Chinese National Essential Public Health Service Package (NEPHSP) has mandated primary health care providers to provide falls prevention for community-dwelling older people. But no implementation framework is available to guide better integration of falls prevention for older people within the primary health care system. METHODS: This is a two-stage online participatory design study consisting of eight workshops with stakeholders from three purposively selected cities. First, two workshops were organised at each study site to jointly develop the framework prototype. Second, to refine, optimise and finalise the prototype via two workshops with all study participants. Data analysis and synthesis occurred concurrently with data collection, supported by Tencent Cloud Meeting software. RESULTS: All participants confirmed that the integration of falls prevention for older people within the NEPHSP was weak and reached a consensus on five opportunities to better integrate falls prevention, including workforce training, community health promotion, health check-ups, health education and scheduled follow-up, during the delivery of NEPHSP. Three regional-tailored prototypes were then jointly developed and further synthesised into a generic implementation framework by researchers and end-users. Guided by this framework, 11 implementation strategies were co-developed under five themes. CONCLUSIONS: The current integration of falls prevention in the NEPHSP is weak. Five opportunities for integrating falls prevention in the NEPHSP and a five-themed implementation framework with strategies are co-identified and developed, using a participatory design approach. These findings may also provide other regions or countries, facing similar challenges, with insights for promoting falls prevention for older people.

KEYPOINTS: The integration of falls prevention for older people was weak in the Chinese PHC system.Five opportunities were identified for better integrating falls prevention for older people in the Chinese PHC system.We developed an implementation framework to strengthen the solid integration of falls prevention in the Chinese PHC system.