Hidden symmetry-induced effective moving double-zero-index metamaterials.

Materials possessing an effective zero refractive index are often associated with Dirac-like cone dispersion at the center of the Brillouin zone (BZ). It has been reported the presence of hidden symmetry-enforced triply degenerate points [nexus points (NP)] away from the Brillouin zone center with the stacked dielectric photonic crystals. The spin-1 Dirac-like dispersion in the xy plane near the nexus point suggests a method for achieving zero refractive index materials. The stacked photonic crystals at the nexus points can be deemed as an effective moving double-zero-index medium (MDZIM) traveling with a speed relative to the laboratory reference. The ability of this moving double-zero-index medium to enable perfect wave tunneling across barriers without reflection has been demonstrated, dependent on the incident waves' specific angular orientations.

New Cytotoxic γ-Lactam Alkaloids from the Mangrove-Derived Fungus Talaromyces hainanensis sp. nov. Guided by Molecular Networking Strategy.

The fungus Talaromyces hainanensis, isolated from the mangrove soil, was characterized as a novel species by morphology observation and phylogenetic analyses. Four new γ-lactam alkaloids talaroilactams A-D (1-4) and two reported compounds harzianic acid (5) and isoharzianic acid (6) were identified from the fungus T. hainanensis WHUF0341, assisted by OSMAC along with molecular networking approaches. Their structures were determined through ECD calculations and spectroscopic analyses. Moreover, the biosynthetic route of 1-4 was also proposed. Compound 1 displayed potent cytotoxicity against HepG2 cell lines, with an IC50 value of 10.75 ± 1.11 µM. In addition, network pharmacology was employed to dissect the probable mechanisms contributing to the antihepatocellular carcinoma effects of compound 1, revealing that cytotoxicity was mainly associated with proteolysis, negative regulation of autophagy, inflammatory response, and the renin-angiotensin system. These results not only expanded the chemical space of natural products from the mangrove associated fungi but also afforded promising lead compounds for developing the antihepatocellular carcinoma agents.

Off-target autophagy inhibition by SHP2 allosteric inhibitors contributes to their anti-tumor activity in RAS-driven cancers.

Aberrant activation of RAS-MAPK signaling is common in cancer, and efforts to inhibit pathway components have yielded drugs with promising clinical activities. Unfortunately, treatment-provoked adaptive resistance mechanisms inevitably develop, limiting their therapeutic potential. As a central node essential for receptor tyrosine kinase mediated RAS activation, SHP2 has emerged as an attractive cancer target. Consequently, many SHP2 allosteric inhibitors are now in clinical testing. Here we discovered a previously unrecognized off-target effect associated with SHP2 allosteric inhibitors. We found that these inhibitors accumulate in the lysosome and block autophagic flux in a SHP2-independent manner. We showed that off-target autophagy inhibition by SHP2 allosteric inhibitors contributes to their anti-tumor activity. We also demonstrated that SHP2 allosteric inhibitors harboring this off-target activity not only suppress oncogenic RAS signaling but also overcome drug resistance such as MAPK rebound and protective autophagy in response to RAS-MAPK pathway blockage. Finally, we exemplified a therapeutic framework that harnesses both the on- and off-target activities of SHP2 allosteric inhibitors for improved treatment of mutant RAS driven and drug resistant malignancies such as pancreatic and colorectal cancers. Brief Summary: SHP2 allosteric inhibitors elicit off-target autophagy blockade that can be exploited for improved treatment of RAS-driven and drug-resistant cancers.

Near-Field Spin Chern Number Quantized by Real-Space Topology of Optical Structures.

The Chern number has been widely used to describe the topological properties of periodic structures in momentum space. Here, we introduce a real-space spin Chern number for the optical near fields of finite-sized structures. This new spin Chern number is intrinsically quantized and equal to the structure's Euler characteristic. The relationship is robust against continuous deformation of the structure's geometry and is irrelevant to the specific material constituents or external excitation. Our Letter enriches topological physics by extending the Chern number to real space, opening exciting possibilities for exploring the real-space topological properties of light.

Topological Photonic Alloy.

We present the new concept of photonic alloy as a nonperiodic topological material. By mixing nonmagnetized and magnetized rods in a nonperiodic 2D photonic crystal configuration, we realized photonic alloys in the microwave regime. Our experimental findings reveal that the photonic alloy sustains nonreciprocal chiral edge states even at very low concentration of magnetized rods. The nontrivial topology and the associated edge states of these nonperiodic systems can be characterized by the winding of the reflection phase. Our results indicate that the threshold concentrations for the investigated system within the first nontrivial band gap to exhibit topological behavior approach zero in the thermodynamic limit for substitutional alloys, while the threshold remains nonzero for interstitial alloys. At low concentration, the system exhibits an inhomogeneous structure characterized by isolated patches of nonpercolating magnetic domains that are spaced far apart within a topologically trivial photonic crystal. Surprisingly, the system manifests chiral edge states despite a local breakdown of time-reversal symmetry rather than a global one. Photonic alloys represent a new category of disordered topological materials, offering exciting opportunities for exploring topological materials with adjustable gaps.

Needs and Constraints for Cardiac Rehabilitation Among Patients with Coronary Heart Disease Within a Community-Based Setting: A Study Based on Focus Group Interviews.

Objective: This study aimed to explore the needs and constraints to cardiac rehabilitation (CR) among patients diagnosed with coronary heart disease (CHD) in a community-based setting, and thereby facilitating the implementation of effective CR programs for this population. Methods: Focus group interviews were used as the primary research methodology. A total of 11 community-dwelling individuals diagnosed with CHD were selected from a community hospital to participate in in-depth interviews, aiming to discern and analyze their requirements and constraints experienced concerning medical resources and healthcare agency. The textual data underwent examination using Colaizzi's method of descriptive data analysis. Results: Deficits existed in the perceptions of patients with CHD within a community-based setting about their condition and CR, and in the social support for this disease. Patients expressed expectations for professional guidance during CR, gained an understanding about the beneficial effects of emotional stability on cognitive function. Patients expressed their thoughts and feelings regarding the diversity of physical exercise options. Two main themes and seven sub-themes were identified: (a) "Insufficient CR resources for patients": Lack of awareness about CHD; inadequate knowledge about secondary prevention/CR; insufficient support from family and friends. (b) "Patient CR initiative": Patient self-adjustment; expectation of professional rehabilitation guidance; stable emotions improving cognition; diverse attitudes and awareness of exercise. Conclusion: For more effective CR, community-based medical teams should provide more comprehensive and individualized rehabilitation programs. They should focus on individual variations and preferences of patients, as well as enhance the autonomy of patients and improve their self-care ability through effective empowerment measures.

MRI radiomics enhances radiologists' ability for characterizing intestinal fibrosis in patients with Crohn's disease.

OBJECTIVES: We aimed to develop MRI-based radiomic models (RMs) to improve the diagnostic accuracy of radiologists in characterizing intestinal fibrosis in patients with Crohn's disease (CD). METHODS: This retrospective study included patients with refractory CD who underwent MR before surgery from November 2013 to September 2021. Resected bowel segments were histologically classified as none-mild or moderate-severe fibrosis. RMs based on different MR sequence combinations (RM1: T2WI and enhanced-T1WI; RM2: T2WI, enhanced-T1WI, diffusion-weighted imaging [DWI], and apparent diffusion coefficient [ADC]); RM3: T2WI, enhanced-T1WI, DWI, ADC, and magnetization transfer MRI [MTI]), were developed and validated in an independent test cohort. The RMs' diagnostic performance was compared to that of visual interpretation using identical sequences and a clinical model. RESULTS: The final population included 123 patients (81 men, 42 women; mean age: 30.26 ± 7.98 years; training cohort, n = 93; test cohort, n = 30). The area under the receiver operating characteristic curve (AUC) of RM1, RM2, and RM3 was 0.86 (p = 0.001), 0.88 (p = 0.001), and 0.93 (p = 0.02), respectively. The decision curve analysis confirmed a progressive improvement in the diagnostic performance of three RMs with the addition of more specific sequences. All RMs performance surpassed the visual interpretation based on the same MR sequences (visual model 1, AUC = 0.65, p = 0.56; visual model 2, AUC = 0.63, p = 0.04; visual model 3, AUC = 0.77, p = 0.002), as well as the clinical model composed of C-reactive protein and erythrocyte sedimentation rate (AUC = 0.60, p = 0.13). CONCLUSIONS: The RMs, utilizing various combinations of conventional, DWI and MTI sequences, significantly enhance radiologists' ability to accurately characterize intestinal fibrosis in patients with CD. CRITICAL RELEVANCE STATEMENT: The utilization of MRI-based RMs significantly enhances the diagnostic accuracy of radiologists in characterizing intestinal fibrosis. KEY POINTS: MRI-based RMs can characterize CD intestinal fibrosis using conventional, diffusion, and MTI sequences. The RMs achieved AUCs of 0.86-0.93 for assessing fibrosis grade. MRI-radiomics outperformed visual interpretation for grading CD intestinal fibrosis.

Mendelian Randomization Analysis of Circulating Cytokines and Risk of Autoimmune Neuroinflammatory Diseases.

Background: Cytokines act a vital role in autoimmune neuroinflammatory diseases (ANDs) with undetermined causal relationships. Mendelian randomization (MR) analysis was performed to estimate the causal effects of circulating levels of cytokines on the risk of ANDs. Methods: The causal relationship between 34 circulating cytokines and 4 kinds of ANDs, including multiple sclerosis (MS), neuromyelitis optica (NOM), chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) were explored using four methods of MR analysis. MR-PRESSO, MR-Egger regression methods and Cochran's Q statistic were utilized to identify the instrumental variables (IVs) with potential pleiotropy and heterogeneity. The Bonferroni correction was used for multiple group comparisons. P-value less than 3.68E-04 (0.05/ (34*4)) was considered statistically significant. Results: Negative causal effects of circulating levels of interleukin (IL)-8 (OR = 0.648, 95% CI: 0.494-0.851, P = 0.002) on risk of MS, chemokine (C-C Motif) ligand (CCL)-5 (OR = 0.295, 95% CI: 0.103-0.841, P = 0.022) and stem cell growth factor-beta (SCGF-ß) (OR = 0.745, 95% CI: 0.565-0.984, P = 0.038) on risk of CIDP, as well as positive causal effects of circulating levels of IL-2 receptor α (IL-2Rα) (OR = 1.216, 95% CI: 1.120-1.320, P = 3.20E-06) and chemokine C-X-C motif ligand (CXCL)-10 (OR = 1.404, 95% CI: 1.094-1.803, P = 0.008) on MS were observed. Nevertheless, only IL-2Rα still had a causal effect on MS after Bonferroni correction. Conclusion: The results identify a genetically predicted causal effect of IL-2Rα, IL-8 and CXCL-10 on MS, CCL-5 and SCGF-ß on CIDP.

Screening of plant growth-promoting rhizobacteria helps alleviate the joint toxicity of PVC+Cd pollution in sorghum plants.

Combined microplastic and heavy metal pollution (CM-HP) has become a popular research topic due to the ability of these pollutants to have complex interactions. Plant growth-promoting rhizobacteria (PGPR) are widely used to alleviate stress from heavy metal pollution in plants. However, the effects and mechanisms by which these bacteria interact under CM-HP have not been extensively studied. In this study, we isolated and screened PGPR from CM-HP soils and analyzed the effects of these PGPR on sorghum growth and Cd accumulation under combined PVC+Cd pollution through pot experiments. The results showed that the length and biomass of sorghum plants grown in PVC+Cd contaminated soil were significantly lower than those grown in soils contaminated with Cd alone, revealing an enhancement in toxicity when the two contaminants were mixed. Seven isolated and screened PGPR strains effectively alleviated stress due to PVC+Cd contamination, which resulted in a significant enhancement in sorghum biomass. PGPR mitigated the decrease in soil available potassium, available phosphorus and alkali-hydrolyzable nitrogen content caused by combined PVC+Cd pollution and increased the contents of these soil nutrients. Soil treatment with combined PVC+Cd pollution and PGPR inoculation can affect rhizosphere bacterial communities and change the composition of dominant populations, such as Proteobacteria, Firmicutes, and Actinobacteria. PICRUSt2 functional profile prediction revealed that combined PVC+Cd pollution and PGPR inoculation affected nitrogen fixation, nitrification, denitrification, organic phosphorus mineralization, inorganic phosphorus solubilization and the composition and abundance of genes related the N and P cycles. The Mantel test showed that functional strain abundance, the diversity index and N and P cycling-related genes were affected by test strain inoculation and were significant factors affecting sorghum growth, Cd content and accumulation. This study revealed that soil inoculation with isolated and screened PGPR can affect the soil inorganic nutrient content and bacterial community composition, thereby alleviating the stress caused by CM-HP and providing a theoretical basis and data support for the remediation of CM-HP.

Association of gene polymorphisms and the decreased expression of long non-coding RNA LOC553103 with rheumatoid arthritis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in many key bioprocesses, including the occurrence and development of rheumatoid arthritis (RA). We aimed to analyze the association of genetic variants of long non-coding RNA LOC553103 and its peripheral blood mononuclear cells (PBMC) expression with RA. METHODS: We enrolled 457 RA patients and 551 healthy controls and conducted a case-control study to analyze the relationship between LOC553103 gene rs272879 and the susceptibility of RA by TaqMan single nucleotide polymorphism genotyping. Among them, we sampled 92 cases and 92 controls, respectively, to detect the PBMC level of LOC553103 using quantitative real-time polymerase chain reaction technology. We explored the association between LOC553103 rs272879 and its PBMC expression levels in 71 RA patients. Mann-Whitney, Chi-square, and Spearman correlation analysis were used for statistical analysis and P-value <.05 was considered statistically significant. RESULTS: The genotype frequency of LOC553103 rs272879 CC was increased, and CG was decreased in RA patients compared to the control group (χ2 = 6.772, P = .034). The LOC553103 expression level in PBMC of RA patients was downregulated compared to healthy control (Z = -4.497, P < .001). Moreover, negative correlations were observed between the PBMC level of LOC553103 and erythrocyte sedimentation rate (rs = -0.262, P = .018), white blood cell count (rs = -0.382, P = .004), platelet (rs = -0.293, P = .030), and disease activity score in 28 joints (rs = -0.271, P = .016) in RA patients. CONCLUSIONS: This study provides the first evidence supporting an association between LOC553103 gene polymorphisms and susceptibility of RA and a relationship of PBMC level of LOC553103 with clinical manifestations and laboratory indicators of RA patients.

Model-based precision dosing and remedial dosing recommendations for delayed or missed doses of isoniazid in Chinese patients with tuberculosis.

AIMS: Isoniazid (INH) has been used as a first-line drug to treat tuberculosis (TB) for more than 50 years. However, large interindividual variability was found in its pharmacokinetics, and effects of nonadherence to INH treatment and corresponding remedy regime remain unclear. This study aimed to develop a population pharmacokinetic (PPK) model of INH in Chinese patients with TB to provide model-informed precision dosing and explore appropriate remedial dosing regimens for nonadherent patients. METHODS: In total, 1012 INH observations from 736 TB patients were included. A nonlinear mixed-effects modelling was used to analyse the PPK of INH. Using Monte Carlo simulations to determine optimal dosage regimens and design remedial dosing regimens. RESULTS: A 2-compartmental model, including first-order absorption and elimination with allometric scaling, was found to best describe the PK characteristics of INH. A mixture model was used to characterize dual rates of INH elimination. Estimates of apparent clearance in fast and slow eliminators were 28.0 and 11.2 L/h, respectively. The proportion of fast eliminators in the population was estimated to be 40.5%. Monte Carlo simulations determined optimal dosage regimens for slow and fast eliminators with different body weight. For remedial dosing regimens, the missed dose should be taken as soon as possible when the delay does not exceed 12 h, and an additional dose is not needed. delay for an INH dose exceeds 12 h, the patient only needs to take the next single dose normally. CONCLUSION: PPK modelling and simulation provide valid evidence on the precision dosing and remedial dosing regimen of INH.

Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system.

The present letter to the editor is related to the study titled 'Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells'. Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

A review of the pharmacological action and mechanism of natural plant polysaccharides in depression.

Depression is a prevalent mental disorder. However, clinical treatment options primarily based on chemical drugs have demonstrated varying degrees of adverse reactions and drug resistance, including somnolence, nausea, and cognitive impairment. Therefore, the development of novel antidepressant medications that effectively reduce suffering and side effects has become a prominent area of research. Polysaccharides are bioactive compounds extracted from natural plants that possess diverse pharmacological activities and medicinal values. It has been discovered that polysaccharides can effectively mitigate depression symptoms. This paper provides an overview of the pharmacological action and mechanisms, intervention approaches, and experimental models regarding the antidepressant effects of polysaccharides derived from various natural sources. Additionally, we summarize the roles and potential mechanisms through which these polysaccharides prevent depression by regulating neurotransmitters, HPA axis, neurotrophic factors, neuroinflammation, oxidative stress, tryptophan metabolism, and gut microbiota. Natural plant polysaccharides hold promise as adjunctive antidepressants for prevention, reduction, and treatment of depression by exerting their therapeutic effects through multiple pathways and targets. Therefore, this review aims to provide scientific evidence for developing polysaccharide resources as effective antidepressant drugs.

Evaluation of the influence of different build angles on the surface characteristics, accuracy, and dimensional stability of the complete denture base printed by digital light processing.

Purpose: This study aims to investigate the influence of the build angle on the surface characteristics, accuracy, and dimensional stability of digital light processing (DLP) printed resin bases. Material and methods: Rectangular and complete denture base samples were fabricated at 0, 45, and 90-degree angles (n = 5 for rectangular samples; n = 10 for maxillary and mandibular denture base samples) using a DLP printer. Surface morphology and roughness were assessed using a profilometer, followed by measuring hydrophilicity with a contact angle meter. Accuracy (trueness and precision) and dimensional stability were evaluated at intervals of 1, 3, 7, 14, 28, and 42 days after base printing using best-fit-alignment and deviation analysis in 3D software. Statistical analysis was performed using one-way ANOVA for surface characteristics (α = 0.05), multi-way ANOVA for accuracy and dimensional stability data, and Tukey's test for post-hoc comparisons. Results: The 0-degree group exhibited significantly lower mean roughness (1.27 ± 0.19 µm) and contact angle (80.50 ± 3.71°) (P < 0.001) compared to the 90-degree and 45-degree groups. The 0-degree build angle led to superior trueness (maxilla: 77.80 ± 9.35 µm, mandible: 61.67 ± 10.32 µm) and precision (maxilla: 27.51 ± 7.43 µm, mandible: 53.50 ± 15.16 µm) compared to other groups (P < 0.001). Maxillary base precision was superior to mandibular base precision (P < 0.001). The maxillary base exhibited less dimensional deviation than the mandibular base. The 90-degree group showed the highest deviation compared to the other two groups, and all groups' deviations increased over time (P < 0.001). Conclusions: The build angle significantly influences the surface characteristics, accuracy, and dimensional stability of DLP-printed denture bases. A 0-degree build angle provides the most favorable performance. The maxillary base displayed superior precision and dimensional stability than the mandibular base.

Hormonal and reproductive factors in relation to the risk of rheumatoid arthritis in women: a prospective cohort study with 223 526 participants.

OBJECTIVE: This study aimed to examine rheumatoid arthritis (RA) risk associated with hormonal and reproductive factors in women from the large cohort of the UK Biobank. METHODS: Data on hormonal and reproductive factors in women were collected from a prospective cohort of 223 526 UK Biobank participants. The potential relationship between reproductive factors and RA risk was assessed using restricted cubic spline. Hazard ratios (HR) were estimated using Cox proportional hazard regressions. RESULTS: During a median follow-up of 12.39 years, 3313 women with RA were identified. Age at menarche >14 years was associated with a greater RA risk (HR 1.13, 95% CI 1.02 to 1.26) compared with menarche at 13. The multiple adjusted HR for RA in women with menopause at <45 years was 1.46. Reproductive years <33 increased the risk of RA (HR 1.39, 95% CI 1.21 to 1.59). Compared with those with 2 children, women with ≥4 children were associated with a higher risk of RA (HR 1.18, 95% CI 1.04 to 1.34). Women who had a hysterectomy (HR 1.40, 95% CI 1.25 to 1.56) or oophorectomy (HR 1.21, 95% CI 1.08 to 1.35) had a higher risk of RA than those without a hysterectomy or oophorectomy. Both hormone replacement therapy (HRT) use (HR 1.46, 95% CI 1.35 to 1.57) and HRT duration (HR 1.02, 95% CI 1.01 to 1.03) were associated with a higher risk of RA. CONCLUSIONS: Some hormonal and reproductive factors were associated with a higher risk of RA. Hormonal and reproductive factors should be considered in risk assessment and formulating management plans in female patients with RA.

The supplementation of Rothia as a potential preventive approach for bone loss in mice with ovariectomy-induced osteoporosis.

There is an inseparable link between bone metabolism and gut microbiota, and the supplementation of probiotics exhibits a significant role in maintaining the homeostasis of gut microbiota and inhibiting bone loss. This study aims to explore the preventive and therapeutic potentials and the specific mechanisms of Rothia on osteoporosis. The mice models of osteoporosis induced by ovariectomy (OVX) were built, and the regular (once a day) and quantitative (200 µL/d) gavage of Rothia was performed for 8 weeks starting from 1 week after OVX. Microcomputed tomography was used to analyze the bone mass and bone microstructure of mice in each group after sacrifice. Histological staining and immunohistochemistry were then applied to identify the expression of pro-inflammatory cytokines, intestinal permeability, and osteogenic and osteoclastic activities of mice. The collected feces of mice in each group were used for 16S rRNA high-throughput sequencing to detect the alterations in composition, abundance, and diversity of gut microbiota. This study demonstrated that the gavage of Rothia alleviated bone loss in mice with OVX-induced osteoporosis, improved OVX-induced intestinal mucosal barrier injury, optimized intestinal permeability (zonula occludens protein 1 and occludin), reduced intestinal inflammation (tumor necrosis factor-α and interleukin-1ß), and regulated imbalance of gut microbiota. Based on "gut-bone" axis, this study revealed that regular and quantitative gavage of Rothia can relieve bone loss in mice with OVX-induced osteoporosis by repairing the intestinal mucosal barrier injury, optimizing the intestinal permeability, inhibiting the release of pro-inflammatory cytokines, and improving the disorder of gut microbiota.

A Novel Cargo Delivery System-AnCar-ExoLaIMTS Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro-inflammatory macrophages via antigen recognition, which is named AnCar-ExoLaIMTS . The data indicate that the phagocytosis efficiencies of pro-inflammatory macrophages for different AnCar-ExoLaIMTS show obvious differences. The AnCar-ExoLaIMTS3 has the best targeting ability for pro-inflammatory macrophages in vitro and in vivo. Mechanically, AnCar-ExoLaIMTS3 can specifically recognize the leucine-rich repeat domain of the TLR4 receptor, and then enter into pro-inflammatory macrophages via the TLR4-mediated receptor endocytosis pathway. Moreover, AnCar-ExoLaIMTS3 can efficiently deliver therapeutic cargo to pro-inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF-1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.

Two adjacent NAC transcription factors regulate fruit maturity date and flavor in peach.

Although maturity date (MD) is an essential factor affecting fresh fruit marketing and has a pleiotropic effect on fruit taste qualities, the underlying mechanisms remain largely unclear. In this study, we functionally characterized two adjacent NAM-ATAF1/2-CUC2 (NAC) transcription factors (TFs), PpNAC1 and PpNAC5, both of which were associated with fruit MD in peach. PpNAC1 and PpNAC5 were found capable of activating transcription of genes associated with cell elongation, cell wall degradation and ethylene biosynthesis, suggesting their regulatory roles in fruit enlargement and ripening. Furthermore, PpNAC1 and PpNAC5 had pleiotropic effects on fruit taste due to their ability to activate transcription of genes for sugar accumulation and organic acid degradation. Interestingly, both PpNAC1 and PpNAC5 orthologues were found in fruit-producing angiosperms and adjacently arranged in all 91 tested dicots but absent in fruitless gymnosperms, suggesting their important roles in fruit development. Our results provide insight into the regulatory roles of NAC TFs in MD and fruit taste.

Gut microbiota from essential tremor patients aggravates tremors in mice.

Background and objective: Essential tremor (ET) lacks effective treatments because its underlying mechanism is largely unknown, but may involve gut microbiota via the microbiome-gut-brain axis. We explored the effects of gut microbiota on ET in mice. Methods: Specific pathogen-free C57BL/6J mice were gavaged with stools from ET patients or matched healthy individuals. After 3 weeks of gavaging, behavioral tests were performed on all mice. Next, each mouse was injected with harmaline to induce tremors. The tremor duration was recorded; the tremor score was estimated every 30 min. Behavioral tests were repeated after modeling. Intestinal tissues and fecal samples of the mice were examined using histology and 16Sr DNA sequencing, respectively. Results: Compared with mice receiving microbiota from healthy controls, mice receiving fecal suspensions from ET patients showed worse performance in the pre-modeling behavioral tests. After modeling, ET-group mice showed significantly greater tremor scores, longer tremor duration, and worse motor performance. They also had significantly lower body weight and lower fecal pellet count. Pathological scoring revealed more severe intestinal lesions in ET-group mice. The 16S rDNA sequencing data revealed significant differences in microbiota indices, and a correlation between these indices and tremors in mice. Functional predictions indicated that the abundance of GABA-related enzymes was altered in ET-group mice. Conclusion: Mice transplanted with gut microbiota from ET patients showed worse performance in behavioral tests. After modeling, ET-group mice presented longer tremor duration, higher tremor score, and worse motor performance. This study provides evidence for gut microbiota dysbiosis that may affect the pathogenesis of ET.

Management of acute carbamazepine poisoning: A narrative review.

Standard management protocols are lacking and specific antidotes are unavailable for acute carbamazepine (CBZ) poisoning. The objective of this review is to provide currently available information on acute CBZ poisoning, including its management, by describing and summarizing various therapeutic methods for its treatment according to previously published studies. Several treatment methods for CBZ poisoning will be briefly introduced, their advantages and disadvantages will be analyzed and compared, and suggestions for the clinical treatment of CBZ poisoning will be provided. A literature search was performed in various English and Chinese databases. In addition, the reference lists of identified articles were screened for additional relevant studies, including non-indexed reports. Non-peer-reviewed sources were also included. In the present review, 154 articles met the inclusion criteria including case reports, case series, descriptive cohorts, pharmacokinetic studies, and in vitro studies. Data on 67 patients, including 4 fatalities, were reviewed. Based on the summary of cases reported in the included articles, the cure rate of CBZ poisoning after symptomatic treatment was 82% and the efficiency of hemoperfusion was 58.2%. Based on the literature review, CBZ is moderately dialyzable and the recommendation for CBZ poisoning is supportive management and gastric lavage. In severe cases, extracorporeal treatment is recommended, with hemodialysis as the first choice.