OTULIN-related conditions: Report of a new case and review of the literature using GenIA.

OTULIN encodes an eponymous linear deubiquitinase (DUB) essential for controlling inflammation as a negative regulator of the canonical NF-κB signaling pathway via the regulation of M1-Ub dynamics. Biallelic loss-of-function (LOF) mutations in OTULIN cause an autosomal recessive condition named Otulin-Related Autoinflammatory Syndrome (ORAS), also known as Otulipenia or AutoInflammation, Panniculitis, and Dermatosis Syndrome (AIPDS). Monoallelic OTULIN LOF, also known as OTULIN Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has been linked to an incompletely penetrant, dominantly inherited susceptibility to invasive Staphylococcal infections. At the same time, a recent novel ORAS-like inflammatory syndrome was described in association with a heterozygous missense mutation that appears to exert dominant negative (DN) effects. In this manuscript, we report the identification of a novel homozygous missense mutation, c.595 T > A; p.(Trp199Arg), in a Moroccan infant with an ORAS phenotype and provide experimental evidence for its pathogenicity. We go on to systematically review the literature for OTULIN-associated conditions by using the GenIA database (www.geniadb.net) to collect, extract and harmonize all clinical, laboratory and functional data for published patients and variants. Our comprehensive synthesis of genotypic, phenotypic, and mechanistic data enables a more in-depth view of the diverse mechanisms and pathways by which the OTULIN pathogenic variants may lead to human immune disease. This review may help variant classification activities and inform future variant evaluation, as well as the development of diagnostic and management guidelines. It also identifies current knowledge gaps and raises additional questions warranting future investigation.

A system review of central nervous system tumors on children in China: epidemiology and clinical characteristics.

BACKGROUND: Central nervous system (CNS) tumors are the most common solid tumors in children and the leading cause of cancer-related death in the latter. Currently, the incidence rate exceeds that of leukemia and ranks first in the incidence of malignant tumors in children. METHODS: The epidemiological data on childhood CNS tumors were collected from the Chinese Cancer Registry Annual Report. The annual percent change (APC) of incidence and mortality-rate changes were estimated via Joinpoint regression. Due to a lack of pertinent data, we performed a system review on the clinical-pathological characteristics in Chinese publications. RESULTS: There was no significant increase in the incidence rate (APC: -0.1, 95% CI: -1.5 to 1.3), but there was a significant increase in the mortality rate (APC: 1.8, 95% CI: 0.3 to 3.4) for childhood CNS tumors. In the subgroup analysis, there were significant increases in both the incidence and mortality rates in rural areas (APC in the incidence: 6.2, 95% CI: 2.4 to 10.2; APC in mortality: 4.4, 95% CI: 0.4 to 8.4). The most common location and type of childhood CNS were, respectively, the cerebral hemisphere (25.5%, 95% CI: 21.7% to 29.4%) and astrocytomas (26.8%, 95% CI: 23.9% to 29.6%). CONCLUSIONS: The epidemiological trends, and the relevant prediction, highlighted the need to pay continual attention to childhood CNS tumors, and the clinicopathology evinced its own distinctive characteristics. Timely detection and effective treatment must be further promoted regarding childhood CNS tumors with a view to decreasing the disease burden, especially in rural areas.

Ac2-26 Reduced Lung Injury After Cardiopulmonary Bypass via the AKT1/GSK3ß/eNOS Pathway.

INTRODUCTION: Cardiopulmonary bypass (CPB) leads to severe inflammation and lung injury. Our previous study showed that Ac2-26 (an active n-terminal peptide of Annexin A1) can reduce acute lung injury. The aim of this study was to evaluate the effect of Ac2-26 on lung injury in CPB rats. METHODS: Forty rats were randomly divided into the sham, CPB, Ac, Ac/serine/threonine kinase 1 (AKT1), and Ac/ glycogen synthase kinase (GSK)-3ß groups. The rats in the sham group only received anesthesia, intubation, and cannulation. The rats in the other 4 groups received the standard CPB procedure. The rats in the CPB, Ac, Ac/AKT1, and Ac/GSK3ß groups were immediately injected with saline, Ac2-26 (1 mg/kg), Ac2-26 combined with short hairpin RNA (AKT1), or Ac2-26 combined with a GSK3ß inhibitor after CPB. At 12 h after the end of CPB, the PaO2/ fraction of inspired oxygen ratio, wet/dry weight ratio and protein content in the bronchoalveolar lavage fluid (BALF) were recorded. The numbers of macrophages and neutrophils in the BALF and blood were determined. Cytokine levels in the blood and BALF were investigated. Lung tissue histology and apoptosis were estimated. The expression of nuclear factor kappa- B, AKT1, GSK3ß, endothelial nitric oxide synthase and apoptosis-related proteins was analyzed. The survival of all the rats was recorded. RESULTS: Compared with the rats in the sham group, all the parameters examined worsened in the rats that received CPB. Compared with those in the CPB group, Ac2-26 significantly improved pulmonary capillary permeability, reduced cytokine levels, and decreased histological scores and apoptosis. The protective effect of Ac2-26 on lung injury was significantly reversed by AKT1 short hairpin RNA or a GSK3ß inhibitor. CONCLUSIONS: Ac2-26 significantly reduced lung injury and inflammation after CPB. The protective effect of Ac2-26 mainly depended on the AKT1/GSK3ß/endothelial nitric oxide synthase pathway.

Breast cancer screening and early diagnosis in China: a systematic review and meta-analysis on 10.72 million women.

BACKGROUND: The incidence of breast cancer among Chinese women has gradually increased in recent years. This study aims to analyze the situation of breast cancer screening programs in China and compare the cancer detection rates (CDRs), early-stage cancer detection rates (ECDRs), and the proportions of early-stage cancer among different programs. METHODS: We conducted a systematic review and meta-analysis of studies in multiple literature databases. Studies that were published between January 1, 2010 and June 30, 2023 were retrieved. A random effects model was employed to pool the single group rate, and subgroup analyses were carried out based on screening model, time, process, age, population, and follow-up method. RESULTS: A total of 35 studies, including 47 databases, satisfied the inclusion criteria. Compared with opportunistic screening, the CDR (1.32‰, 95% CI: 1.10‰-1.56‰) and the ECDR (0.82‰, 95% CI: 0.66‰-0.99‰) were lower for population screening, but the proportion of early-stage breast cancer (80.17%, 95% CI: 71.40%-87.83%) was higher. In subgroup analysis, the CDR of population screening was higher in the urban group (2.28‰, 95% CI: 1.70‰-2.94‰), in the breast ultrasonography (BUS) in parallel with mammography (MAM) group (3.29‰, 95% CI: 2.48‰-4.21‰), and in the second screening follow-up group (2.47‰, 95% CI: 1.64‰-3.47‰), and the proportion of early-stage breast cancer was 85.70% (95% CI: 68.73%-97.29%), 88.18% (95% CI: 84.53%-91.46%), and 90.05% (95% CI: 84.07%-94.95%), respectively. CONCLUSION: There were significant differences between opportunistic and population screening programs. The results of these population screening studies were influenced by the screening process, age, population, and follow-up method. In the future, China should carry out more high-quality and systematic population-based screening programs to improve screening coverage and service.

Meta-analysis and systematic review of the relationship between sex and the risk or incidence of poststroke aphasia and its types.

OBJECTIVE: To analyse and discuss the association of gender differences with the risk and incidence of poststroke aphasia (PSA) and its types, and to provide evidence-based guidance for the prevention and treatment of poststroke aphasia in clinical practice. DATA SOURCES: Embase, PubMed, Cochrane Library and Web of Science were searched from January 1, 2002, to December 1, 2023. STUDY SELECTION: Including the total number of strokes, aphasia, the number of different sexes or the number of PSA corresponding to different sex. DATA EXTRACTION: Studies with missing data, aphasia caused by nonstroke and noncompliance with the requirements of literature types were excluded. DATA SYNTHESIS: 36 papers were included, from 19 countries. The analysis of 168,259 patients with stroke and 31,058 patients with PSA showed that the risk of PSA was 1.23 times higher in female than in male (OR = 1.23, 95% CI = 1.19-1.29, P < 0.001), with a prevalence of PSA of 31% in men and 36% in women, and an overall prevalence of 34% (P < 0.001). Analysis of the risk of the different types of aphasia in 1,048 patients with PSA showed a high risk in females for global, broca and Wenicke aphasia, and a high risk in males for anomic, conductive and transcortical aphasia, which was not statistically significant by meta-analysis. The incidence of global aphasia (males vs. females, 29% vs. 32%) and broca aphasia (17% vs 19%) were higher in females, and anomic aphasia (19% vs 14%) was higher in males, which was statistically significant (P < 0.05). CONCLUSIONS: There are gender differences in the incidence and types of PSA. The risk of PSA in female is higher than that in male.

Effects of subtle variation in forest canopy openness on cache pilferage and its implications for forest regeneration.

Scatter-hoarding rodents play important roles in plant regeneration and species coexistence in many forest ecosystems. Cache pilferage, the behavior of rodents seeking or relocating seeds cached by other individuals, is ubiquitous during the scatter-hoarding process. The effects of canopy openness on cache pilferage have received considerable attention, most of which have focused on the comparison between full canopy cover and completely open areas, such as forest gaps. However, little attention has been given to whether the subtle variation in forest canopy openness affects cache pilferage, although subtle variation in light environments exists in many forests, especially tropical and subtropical forests, where the overall canopy is large and the forest window is relatively small. Here, we directly tested these questions by simulating 400 artificial caches, each containing one seed from four selected tree species, in a subtropical forest in southwestern China. The overall canopy openness of the forest was relatively small (with a mean value of 11.1%), but subtle spatial variation still existed (ranging from 5.7% to 19.5%). Overall, caches with lower canopy openness were more likely to be pilfered and removed faster, although not all species showed the same pattern. Our study highlights that subtle variation in forest canopy openness, even in a closed primary forest, has significant effects on cache pilferage by rodents, which may influence the following seed germination and forest regeneration processes. Additionally, seedling species composition may further be altered because the canopy effects on cache pilferage are species-specific.

Structurally diverse diterpenoids and phenanthrene derivatives from the roots of Baliospermumsolanifolium.

Ten undescribed diterpenoids (1-10) and three undescribed phenanthrene derivatives (11-13), together with seven known compounds, were isolated from the roots of Baliospermum solanifolium. Their structures were determined by a combination of spectroscopic data analysis, electronic circular dichroism calculations and single-crystal X-ray diffraction studies. Compounds 1-7 (baliosperoids A-G) represent the examples of 20-nor-ent-podocarpane class first discovered in nature. In particular, compound 7 possesses a unique 2,3-seco ring system incorporating γ-butanolide moiety. All isolates were assessed for their cytotoxic activities against HT-29, HCT-116, HCT-15, MCF-7, and A549 cell lines as well as their inhibitory effects on lipopolysaccharide-induced NO production in RAW264.7 cells. Compound 1, a 20-nor-ent-podocarpane-type diterpenoid possessing a Δ1,2 double bond, not only exhibited considerable proliferation inhibition against five human cancer cell lines, with IC50 values ranging from 4.13 to 23.45 µM, but also displayed the most potent inhibitory activity on NO production with IC50 value at the nanomolar level (0.63 ± 0.21 µM).

A novel NTRK1 splice site variant causing congenital insensitivity to pain with anhidrosis in a Chinese family.

Background: Congenital insensitivity to pain with anhidrosis (CIPA, OMIM #256800), also known as hereditary sensory and autonomic neuropathy type Ⅳ (HSAN-IV), is a rare autosomal recessive disorder characterized by recurrent episodic fevers, anhidrosis, insensitivity to noxious stimuli, self-mutilating behavior and intellectual disability. CIPA can be caused by the variants in NTRK1 gene, which encodes a high-affinity tyrosine kinase receptor for nerve growth factor. To ascertain the hereditary cause of a patient with CIPA accompanied by the additional symptoms of mild growth retardation, prone to fracture, underdeveloped nails of fingers and toes, irregular tooth alignment, enamel hypoplasia, postoperative wound healing difficulty, hand and limb deformity, and dislocation of hip joint, whole exome sequencing was used and revealed a compound heterozygous variant in NTRK1. Methods: DNA was extracted from peripheral blood samples of pediatric patients and their parents, and subjected to comprehensive analysis using whole-exome sequencing (WES), followed by verification of variant sites in the NTRK1 gene through Sanger sequencing. To elucidate the functional impact of the newly discovered variants, an in vitro experimental system was established. Splicing analysis was conducted using PCR and Sanger sequencing, while expression levels were assessed through qPCR and Western blot techniques. Results: One hotspot variant c.851-33T>A(ClinVar ID: 21308) and a novel variant c.850 + 5G>A(ClinVar ID:3069176) was inherited from her father and mother, respectively, identified in the affected individuals. The c.850 + 5G>A variant in NTRK1 resulted in two forms of aberrant mRNA splicing: 13bp deletion (c.838_850del13, p. Val280Ser fs180) and 25bp deletion (826_850del25, p. Val276Ser fs180) in exon 7, both leading to a translational termination at a premature stop codon and forming a C-terminal truncated protein. The expression of two abnormal splicing isoforms was decreased both in the level of mRNA and protein. Conclusion: In conclusion, this study elucidated the genetic cause of a patient with CIPA and identified a novel variant c.850 + 5G>A in NTRK1, which broadened the and enriched the NTRK1 mutation spectrum.

Assessment of serum vitamin D levels in children aged 0-17 years old in a Chinese population: a comprehensive study.

Vitamin D deficiency and insufficiency pose global public health challenges, yet research on serum vitamin D levels in the 0-17-year-old age group in southeastern China remains limited. This study aimed to fill this gap by investigating serum 25(OH)D levels in children in the region aged 0-17 years, contributing crucial data for understanding vitamin D nutritional status. Liquid chromatography‒mass spectrometry/mass spectrometry (LC‒MS/MS) technology was used. Vitamin D testing was integrated into routine diagnostic procedures for 11,116 children in Wujiang District, Suzhou City. Among the 0-17-year age group, comprising 6348 boys and 4768 girls, the prevalence of serum 25(OH)D deficiency and insufficiency was 21.4% and 31.0%, respectively. The median serum 25(OH)D concentration was 29.72 ng/mL (21.84-39.84 ng/mL) in boys compared to 28.48 ng/mL (20.65-39.23 ng/mL) in girls. Seasonal variations were observed, with median serum 25(OH)D concentrations of 29.02 ng/mL (20.73-39.72 ng/mL) in spring, 28.79 ng/mL (21.53-39.37 ng/mL) in summer, 30.12 ng/mL (22.00-39.70 ng/mL) in autumn, and 28.58 ng/mL (19.97-39.46 ng/mL) in winter. Statistically significant differences were noted in the serum 25(OH)D levels during autumn and winter. In conclusion, the rate of adequate vitamin D levels in local children was 47.5%, revealing a relatively high prevalence of vitamin D deficiency (21.4%) and insufficiency (31.0%), especially during the post-preschool period. Advocating for vitamin D supplementation in children is crucial for ensuring adequate vitamin D support.

The efficacy and safety of enhanced recovery after surgery (ERAS) Program in laparoscopic distal gastrectomy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Although ERAS Program had some advantages in laparoscopic distal gastrectomy (LDG), its efficacy and safety remained unclear. We conducted a systematic review and meta-analysis to assess the efficacy and safety of the ERAS group and the traditional care (TC) group in LDG. METHODS: Multiple databases were retrieved from 1 January 2000 to 30 April 2023. The risk ratio (RR), standardized mean difference (SMD) and their 95% confidence interval (CI) were used to estimate the results. RESULTS: Our meta-analysis contained 17 randomized controlled trials (RCTs) studies, which comprised 1468 patients. Regarding efficacy, the ERAS group had significantly shorter postoperative time to first flatus (SMD = -1.29 [95% CI: -1.68, -0.90]), shorter time to first defecation (SMD = -1.26 [95% CI: -1.90, -0.61]), shorter hospital stays (SMD = -0.99 [95% CI: -1.34, -0.63]), and lower hospitalization costs (SMD = -1.17 [95% CI: -1.86, -0.48]) compared to the TC group. Furthermore, in the ERAS group, C-reactive protein levels were lower on postoperative days 1, 3 or 4, and 7; albumin levels were higher on postoperative days 3 or 4 and 7; and interleukin-6 levels were lower on postoperative days 1 and 3. Regarding safety, the overall postoperative complication rate was lower in the ERAS group (RR: 0.76 [95% CI: 0.60, 0.97]), but there was no significant difference in the individual postoperative complication rate. Other indicators were also not statistically significant. CONCLUSION: The combination of ERAS Program with laparoscopy surgery was safe and effective for the perioperative management of patients with distal gastric cancer.

Dual-modal analysis of cis-diols in traditional Chinese medicine via boronic acid incorporated metal organic frameworks.

In this study, a boronic acid incorporated metal organic frameworks (inBA-MIL-100) were prepared via metal-ligand-fragment co-assembly strategy. The prepared frameworks can be served either as enrichment sorbent or SALDI-MS matrix for cis-diol containing molecules. Thus, a dual-modal analysis of cis-diols in traditional Chinese medicine has been established. Several significant advantages of the proposed strategy have been experimentally demonstrated, including high selectivity, high binding capacity (70 mg/g), good generality (5-250 µg/mL for HPLC based sample preparation, 10-500 ng/mL for SALDI-MS), high sensitivity (LOD: 180 ng/mL for HPLC based sample preparation, 5 ng/mL for SALDI-MS) and reliable quantification (RSD<3 % for HPLC based sample preparation, RSD<12 % for SALDI-MS) performance. Finally, the successful analysis of various cis-diols (active component and mycotoxin) in various Chinese traditional medicine was also achieved.

Incorporation of ascorbic acid in chitosan-based coating combined with plasma-activated water: A technology for quality preservation of red grapes after simulated transportation.

Red grapes possess multiple bioactivities but are highly susceptible to spoilage due to the lack of efficient preservation techniques. Plasma-activated water (PAW) treatment and the incorporation of antioxidants in bio-based coatings are promising methods for preserving produce. In this study, we tested a novel combination by incorporating ascorbic acid (AA) into a chitosan-based edible coating (CH) and combining it with plasma-activated water (PAW) treatment (CA-PAW) before simulating transport vibrations to extend the shelf-life of red grapes. The results from storage at 4 °C for 20 d indicated that the CA-PAW treatment reduced microbial counts by 2.62 log10 CFU/g for bacteria, 1.72 log10 CFU/g for yeasts and molds, and 1.1 log10 CFU/g for coliforms, in comparison to the control group treated with sterile deionized water. Total phenols and total flavonoid content were the highest observed, at 111.2 mg GAE/100 g and 262.67 mg RE/100 g, respectively. This treatment also inhibited water migration and erosion, and reduced damage to cell structure. Microstructural observations revealed that the CH coating on the surface of red grapes diminished the degradation of bioactive components. In conclusion, the CA-PAW treatment effectively inhibited the adverse physiological changes caused by vibration and mechanical damage to red grapes, maintained their nutritional and sensory qualities, and extended the shelf life by at least 8 d.

Multiunit Frontal Eye Field Activity Codes the Visuomotor Transformation, But Not Gaze Prediction or Retrospective Target Memory, in a Delayed Saccade Task.

Single-unit (SU) activity-action potentials isolated from one neuron-has traditionally been employed to relate neuronal activity to behavior. However, recent investigations have shown that multiunit (MU) activity-ensemble neural activity recorded within the vicinity of one microelectrode-may also contain accurate estimations of task-related neural population dynamics. Here, using an established model-fitting approach, we compared the spatial codes of SU response fields with corresponding MU response fields recorded from the frontal eye fields (FEFs) in head-unrestrained monkeys (Macaca mulatta) during a memory-guided saccade task. Overall, both SU and MU populations showed a simple visuomotor transformation: the visual response coded target-in-eye coordinates, transitioning progressively during the delay toward a future gaze-in-eye code in the saccade motor response. However, the SU population showed additional secondary codes, including a predictive gaze code in the visual response and retention of a target code in the motor response. Further, when SUs were separated into regular/fast spiking neurons, these cell types showed different spatial code progressions during the late delay period, only converging toward gaze coding during the final saccade motor response. Finally, reconstructing MU populations (by summing SU data within the same sites) failed to replicate either the SU or MU pattern. These results confirm the theoretical and practical potential of MU activity recordings as a biomarker for fundamental sensorimotor transformations (e.g., target-to-gaze coding in the oculomotor system), while also highlighting the importance of SU activity for coding more subtle (e.g., predictive/memory) aspects of sensorimotor behavior.

Effects of plasma-activated water combined with ultrasonic treatment of corn starch on structural, thermal, physicochemical, functional, and pasting properties.

In this study, corn starch was used as the raw material, and modified starch was prepared using a method combining plasma-activated water and ultrasound treatment (PUL). This method was compared with treatments using plasma-activated water (PAW) and ultrasound (UL) alone. The structure, thermal, physicochemical, pasting, and functional properties of the native and treated starches were evaluated. The results indicated that PAW and UL treatments did not alter the shape of the starch granules but caused some surface damage. The PUL treatment increased the starch gelatinization temperature and enthalpy (from 11.22 J/g to 13.13 J/g), as well as its relative crystallinity (increased by 0.51 %), gel hardness (increased by 16.19 %) compared to untreated starch, without inducing a crystalline transition. The PUL treatment resulted in a whitening of the samples. The dual treatment enhanced the thermal stability of the starch paste, which can be attributed to the synergistic effect between PAW and ultrasound (PAW can modify the starch structure at a molecular level, while ultrasound can further disrupt the granule weak crystalline structures, leading to improved thermal properties). Furthermore, FTIR results suggested significant changes in the functional groups related to the water-binding capacity of starch, and the order of the double-helical structure was disrupted. The findings of this study suggest that PUL treatment is a promising new green modification technique for improving the starch structure and enhancing starch properties. However, further research is needed to tailor the approach based on the specific properties of the raw material.

Autophagic degradation of DHCR7 activates AKT3 and promotes sevoflurane-induced hippocampal neuroinflammation in neonatal mice.

Repeated sevoflurane exposure in neonatal mice triggers neuroinflammation with detrimental effects on cognitive function. Yet, the mechanism of the sevoflurane-induced cytokine response is largely unknown. In this study, we reveal that 3-MA, an autophagy inhibitor, attenuated the sevoflurane-induced neuroinflammation and cognitive dysfunction, including the decreased freezing time and fewer platform crossings, in the neonate mice. 3-Methyladenine (3-MA) suppressed sevoflurane-induced expression of interleukin-6 and tumor necrosis factor-alpha in vitro. Moreover, sevoflurane activates IRF3, facilitating cytokine transcription in an AKT3-dependent manner. Mechanistically, sevoflurane-induced autophagic degradation of dehydrocholesterol-reductase-7 (DHCR7) resulted in accumulations of its substrate 7-dehydrocholesterol (7-DHC), mimicking the effect of sevoflurane on AKT3 activation and IRF3-driven cytokine expression. 3-MA significantly reversed sevoflurane-induced DHCR7 degradation, AKT phosphorylation, IRF3 activation, and the accumulation of 7-DHC in the hippocampal CA1 region. These findings pave the way for additional investigations aimed at developing novel strategies to mitigate postoperative cognitive impairment in pediatric patients.

Low hysteresis zwitterionic supramolecular polymer ion-conductive elastomers with anti-freezing properties, high stretchability, and self-adhesion for flexible electronic devices.

The fabrication of stretchable ionic conductors with low hysteresis and anti-freezing properties to enhance the durability and reliability of flexible electronics even at low temperatures remains an unmet challenge. Here, we report a facile strategy to fabricate low hysteresis, high stretchability, self-adhesion and anti-freezing zwitterionic supramolecular polymer ion-conductive elastomers (ICEs) by photoinitiated polymerization of aqueous precursor solutions containing a newly designed zwitterionic monomer carboxybetaine ureido acrylate (CBUIA) followed by solvent evaporation. The resultant poly(carboxybetaine ureido acrylate) (PCBUIA) ICEs are highly stretchable and self-adhesive owing to the presence of strong hydrogen bonds between ureido groups and dipole-dipole interactions of zwitterions. The zwitterion groups on the polymer side chains and loaded-lithium chloride endow PCBUIA ICEs with excellent anti-freezing properties, demonstrating mechanical flexibility and ionic transport properties even at a low temperature (-20 °C). Remarkably, the PCBUIA ICEs demonstrate a low hysteresis (≈10%) during cyclic mechanical loading-unloading (≤500%), and are successfully applied as wearable strain sensors and triboelectric nanogenerators (TENGs) for energy harvesting and human motion monitoring. In addition, the PCBUIA ICE-based TENG was used as a wireless sensing terminal for Internet of Things smart devices to enable wireless sensing of finger motion state detection.

The Unprecedented Biodegradable Polyzwitterion: A Removal-Free Patch for Accelerating Infected Diabetic Wound Healing.

Zwitterionic polymers have emerged as an important class of biomaterials to construct wound dressings and antifouling coatings over the past decade due to their excellent hydrophilicity. However, all the reported zwitterionic polymers as wound dressings are nondegradable because of noncleavable carbon─carbon bonding backbones, and must be removed periodically after treatment to avoid hypoxia in the wound, thus leading to potential secondary injury. In this work, a biodegradable polyzwitterion patch is fabricated for the first time by ring-opening polymerization of carboxybetaine dithiolane (CBDS), which is self-crosslinked via inter-amide hydrogen bonds and zwitterionic dipole-dipole interactions on the side chains. The unprecedented polyCBDS (PCBDS) patch demonstrates enough ductility owing to the intermolecular physical interactions to fully cover irregular wounds, also showing excellent biodegradability and antifouling performance resulted from the existence of disulfide bonds and carboxybetaine groups. Besides, the PCBDS degradation-induced released CBDS owns potent antioxidant and antibacterial activities. This PCBDS patch is used as a diabetic wound dressing, inhibiting bacterial adhesion on the external surface, and its degradation products can exactly kill bacteria and scavenge excessive reactive oxygen species (ROS) at the wound site to regulate local microenvironment, including regulation of cytokine express and macrophage polarization, accelerating infected diabetic wound repair, and also avoiding the potential secondary injury.

Bcl-xL mediates interferon-beta secretion by protease-activated receptor 2 deficiency through the mitochondrial permeability transition pore in colorectal cancer metastasis.

Cellular plasticity and immune escape are synergistic drivers of tumor colonization in metastatic organs. Activation of protease-activated receptor 2 (PAR2) signaling promotes metastasis of colorectal carcinoma (CRC). The role of PAR2 in regulating the immune microenvironment and cancer progression remains unclear. We demonstrated that the regulation of liver metastasis by PAR2 requires a competent immune system. PAR2 knockdown enhanced liver infiltration of activated CD8+ T cells prior to metastatic foci formation in an interferon receptor-dependent manner. PAR2 depletion increased interferon (IFN)-ß production via the cGAS-STING and RIG-1 pathways. PAR2 inhibition increased mitochondrial permeability and cytosolic accumulation of mitochondrial DNA, which was reversed by Bcl-xL expression. Strikingly, shRNA against PAR2 with an immune checkpoint blocker (ICB) acted synergistically to suppress liver metastasis. Analysis of single-cell sequence data and 24 paired samples confirmed the regulatory effect of PAR2 on the metastatic immune environment in human CRC. Therefore, PAR2 signaling is involved in stabilizing the mitochondrial membrane and regulating the immune microenvironment through IFN-ß during liver metastasis in CRC. The synergistic effect of the PAR2 inhibitor and ICB provides a potential therapeutic strategy for metastatic CRC treatment.

Impact of task-oriented training based on acupuncture rehabilitation on upper extremity function and quality of life of patients with early stroke.

BACKGROUND: Eighty percent of stroke patients develop upper limb dysfunction, especially hand dysfunction, which has a very slow recovery, resulting in economic burden to families and society. AIM: To investigate the impact of task-oriented training based on acupuncture therapy on upper extremity function in patients with early stroke. METHODS: Patients with early stroke hemiplegia who visited our hospital between January 2021 and October 2022 were divided into a control group and an observation group, each with 50 cases. The control group underwent head acupuncture plus routine upper limb rehabilitation training (acupuncture therapy). In addition to acupuncture and rehabilitation, the observation group underwent upper limb task-oriented training (30 min). Each group underwent treatment 5 d/wk for 4 wk. Upper extremity function was assessed in both groups using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Wolf Motor Function Rating Scale (WMFT), modified Barthel Index (MBI), and Canadian Occupational Performance Measure (COPM). Quality of life was evaluated using the Short-Form 36-Item Health Survey (SF-36). Clinical efficacy of the interventions was also evaluated. RESULTS: Before intervention, no significant differences were observed in the FMA-UE, MBI, and WMFT scores between the two groups (P > 0.05). After intervention, the FMA-UE, WMFT, MBI, COPM-Functional Mobility and Satisfaction, and SF-36 scores increased in both groups (P < 0.05), with even higher scores in the observation group (P < 0.05). The observation group also obtained a higher total effective rate than the control group (P < 0.05). CONCLUSION: Task-oriented training based on acupuncture rehabilitation significantly enhanced upper extremity mobility, quality of life, and clinical efficacy in patients with early stroke.

Distinct molecular profiles drive multifaceted characteristics of colorectal cancer metastatic seeds.

Metastasis of primary tumors remains a challenge for early diagnosis and prevention. The cellular properties and molecular drivers of metastatically competent clones within primary tumors remain unclear. Here, we generated 10-16 single cell-derived lines from each of three colorectal cancer (CRC) tumors to identify and characterize metastatic seeds. We found that intrinsic factors conferred clones with distinct metastatic potential and cellular communication capabilities, determining organ-specific metastasis. Poorly differentiated or highly metastatic clones, rather than drug-resistant clones, exhibited poor clinical prognostic impact. Personalized genetic alterations, instead of mutation burden, determined the occurrence of metastatic potential during clonal evolution. Additionally, we developed a gene signature for capturing metastatic potential of primary CRC tumors and demonstrated a strategy for identifying metastatic drivers using isogenic clones with distinct metastatic potential in primary tumors. This study provides insight into the origin and mechanisms of metastasis and will help develop potential anti-metastatic therapeutic targets for CRC patients.