Small RNA SmsR1 modulates acidogenicity and cariogenic virulence by affecting protein acetylation in Streptococcus mutans.

Post-transcriptional regulation by small RNAs and post-translational modifications (PTM) such as lysine acetylation play fundamental roles in physiological circuits, offering rapid responses to environmental signals with low energy consumption. Yet, the interplay between these regulatory systems remains underexplored. Here, we unveil the cross-talk between sRNAs and lysine acetylation in Streptococcus mutans, a primary cariogenic pathogen known for its potent acidogenic virulence. Through systematic overexpression of sRNAs in S. mutans, we identified sRNA SmsR1 as a critical player in modulating acidogenicity, a key cariogenic virulence feature in S. mutans. Furthermore, combined with the analysis of predicted target mRNA and transcriptome results, potential target genes were identified and experimentally verified. A direct interaction between SmsR1 and 5'-UTR region of pdhC gene was determined by in vitro binding assays. Importantly, we found that overexpression of SmsR1 reduced the expression of pdhC mRNA and increased the intracellular concentration of acetyl-CoA, resulting in global changes in protein acetylation levels. This was verified by acetyl-proteomics in S. mutans, along with an increase in acetylation level and decreased activity of LDH. Our study unravels a novel regulatory paradigm where sRNA bridges post-transcriptional regulation with post-translational modification, underscoring bacterial adeptness in fine-tuning responses to environmental stress.

Radiomics analysis of intratumoral and different peritumoral regions from multiparametric MRI for evaluating HER2 status of breast cancer: A comparative study.

Purpose: To investigate the potential of radiomics signatures (RSs) from intratumoral and peritumoral regions on multiparametric magnetic resonance imaging (MRI) to noninvasively evaluate HER2 status in breast cancer. Method: In this retrospective study, 992 patients with pathologically confirmed breast cancers who underwent preoperative MRI were enrolled. The breast cancer lesions were segmented manually, and the intratumor region of interest (ROIIntra) was dilated by 2, 4, 6 and 8 mm (ROIPeri2mm, ROIPeri4mm, ROIPeri6mm, and ROIPeri8mm, respectively). Quantitative radiomics features were extracted from dynamic contrast-enhanced T1-weighted imaging (DCE-T1), fat-saturated T2-weighted imaging (T2) and diffusion-weighted imaging (DWI). A three-step procedure was performed for feature selection, and RSs were constructed using a support vector machine (SVM) to predict HER2 status. Result: The best single-area RSs for predicting HER2 status were DCE_Peri4mm-RS, T2_Peri4mm-RS, and DWI_Peri4mm-RS, yielding areas under the curve (AUCs) of 0.716 (95% confidence interval (CI), 0.648-0.778), 0.706 (95% CI, 0.637-0.768), and 0.719 (95% CI, 0.651-0.780), respectively, in the test set. The optimal RSs combining intratumoral and peritumoral regions for evaluating HER2 status were DCE-T1_Intra + DCE_Peri4mm-RS, T2_Intra + T2_Peri6mm-RS and DWI_Intra + DWI_Peri4mm-RS, with AUCs of 0.752 (95% CI, 0.686-0.810), 0.754 (95% CI, 0.688-0.812) and 0.725 (95% CI, 0.657-0.786), respectively, in the test set. Combining three sequences in the ROIIntra, ROIPeri2mm, ROIPeri4mm, ROIPeri6mm and ROIPeri8mm areas, the optimal RS was DCE-T1_Peri4mm + T2_Peri4mm + DWI_Peri4mm-RS, achieving an AUC of 0.795 (95% CI, 0.733-0.849) in the test set. Conclusion: This study systematically explored the influence of the intratumoral region, different peritumoral sizes and their combination in radiomics analysis for predicting HER2 status in breast cancer based on multiparametric MRI and found the optimal RS.

Calcineurin regulates synaptic Ca2+-permeable AMPA receptors in hypothalamic presympathetic neurons via α2δ-1-mediated GluA1/GluA2 assembly.

Hypertension is a major adverse effect of calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporine, used clinically as immunosuppressants. Calcineurin inhibitor-induced hypertension (CIH) is linked to augmented sympathetic output from the hypothalamic paraventricular nucleus (PVN). GluA2-lacking, Ca2+-permeable AMPA receptors (CP-AMPARs) are a key feature of glutamatergic synaptic plasticity, yet their role in CIH remains elusive. Here, we found that systemic administration of FK506 in rats significantly increased serine phosphorylation of GluA1 and GluA2 in PVN synaptosomes. Strikingly, FK506 treatment reduced GluA1/GluA2 heteromers in both synaptosomes and endoplasmic reticulum-enriched fractions from the PVN. Blocking CP-AMPARs with IEM-1460 induced a larger reduction of AMPAR-mediated excitatory postsynaptic current (AMPAR-EPSC) amplitudes in retrogradely labelled, spinally projecting PVN neurons in FK506-treated rats than in vehicle-treated rats. Furthermore, FK506 treatment shifted the current-voltage relationship of AMPAR-EPSCs from linear to inward rectification in labelled PVN neurons. FK506 treatment profoundly enhanced physical interactions of α2δ-1 with GluA1 and GluA2 in the PVN. Inhibiting α2δ-1 with gabapentin, α2δ-1 genetic knockout, or disrupting α2δ-1-AMPAR interactions with an α2δ-1 C terminus peptide restored GluA1/GluA2 heteromers in the PVN and diminished inward rectification of AMPAR-EPSCs in labelled PVN neurons induced by FK506 treatment. Additionally, microinjection of IEM-1460 or α2δ-1 C terminus peptide into the PVN reduced renal sympathetic nerve discharges and arterial blood pressure elevated in FK506-treated rats but not in vehicle-treated rats. Thus, calcineurin in the hypothalamus constitutively regulates AMPAR subunit composition and phenotypes by controlling GluA1/GluA2 interactions with α2δ-1. Synaptic CP-AMPARs in PVN presympathetic neurons contribute to augmented sympathetic outflow in CIH. KEY POINTS: Systemic treatment with the calcineurin inhibitor increases serine phosphorylation of synaptic GluA1 and GluA2 in the PVN. Calcineurin inhibition enhances the prevalence of postsynaptic Ca2+-permeable AMPARs in PVN presympathetic neurons. Calcineurin inhibition potentiates α2δ-1 interactions with GluA1 and GluA2, disrupting intracellular assembly of GluA1/GluA2 heterotetramers in the PVN. Blocking Ca2+-permeable AMPARs or α2δ-1-AMPAR interactions in the PVN attenuates sympathetic outflow augmented by the calcineurin inhibitor.

Bu-Shen-Ning-Xin decoction inhibits macrophage activation to ameliorate premature ovarian insufficiency-related osteoimmune disorder via FSH/FSHR pathway.

Limited studies are associated with premature ovarian insufficiency (POI)-related osteoimmune disorder currently. Bu-Shen-Ning-Xin decoction (BSNXD) displayed a favorable role in treating postmenopausal osteoporosis. However, its impact on the POI-related osteoimmune disorder remains unclear. The study primarily utilized animal experiments and network pharmacology to investigate the effects and underlying mechanisms of BSNXD on the POI-related osteoimmune disorder. First, a 4-vinylcyclohexene dioxide (VCD)-induced POI murine model was conducted to explore the therapeutical action of BSNXD. Second, we analyzed the active compounds of BSNXD and predicted their potential mechanisms for POI-related osteoimmune disorder via network pharmacology, further confirmed by molecular biology experiments. The results demonstrated that VCD exposure led to elevated follicle-stimulating hormone (FSH) levels, a 50% reduction in the primordial follicles, bone microstructure changes, and macrophage activation, indicating an osteoimmune disorder. BSNXD inhibited macrophage activation and osteoclast differentiation but did not affect serum FSH and estradiol levels in the VCD-induced POI model. Network pharmacology predicted the potential mechanisms of BSNXD against the POI-related osteoimmune disorder involving tumor necrosis factor α and MAPK signaling pathways, highlighting BSNXD regulated inflammation, hormone, and osteoclast differentiation. Further experiments identified BSNXD treatment suppressed macrophage activation via downregulating FSH receptor (FSHR) expression and inhibiting the phosphorylation of ERK and CCAAT enhancer binding proteins ß. In conclusion, BSNXD regulated POI-related osteoimmune disorder by suppressing the FSH/FSHR pathway to reduce macrophage activation and further inhibiting osteoclastogenesis.

RNF31 alleviates liver steatosis by promoting p53/BNIP3-related mitophagy in hepatocytes.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is one of the liver illnesses that may be affected by mitophagy, which is the selective removal of damaged mitochondria. RNF31, an E3 ubiquitin ligase, is carcinogenic in many malignancies. However, the influence of RNF31 on mitochondrial homeostasis and NAFLD development remains unknown. METHODS: Oleic-palmitic acid treated hepatocytes and high-fat diet (HFD)-fed mice were established to observe the effect of RNF31 on hepatocyte mitophagy and steatosis. Mitophagy processes were comprehensively assessed by mt-Keima fluorescence imaging, while global changes in hepatic gene expression were measured by RNA-seq. RESULTS: The present study discovered a reduction in RNF31 expression in lipotoxic hepatocytes with mitochondrial dysfunction. The observed decrease in RNF31 expression was associated with reduced mitochondrial membrane potential, disturbed mitophagy, and increased steatosis. Additionally, the findings indicated that RNF31 is a pivotal factor in the initiation of mitophagy and the facilitation of mitochondrial homeostasis, resulting in a decrease in steatosis in lipotoxic hepatocytes. Mechanistically, RNF31 enhanced p53 ubiquitination and subsequent proteasomal degradation. Down-regulation of p53 led to increased expression of the mitophagy receptor protein BCL2 and adenovirus E1B 19 kDa-interacting protein 3 (BNIP3), thereby promoting mitophagy in hepatocytes. Furthermore, it was demonstrated that the transportation of RNF31 via small extracellular vesicles derived from mesenchymal stem cells (referred to as sEV) had a substantial influence on reducing hepatic steatosis and restoring liver function in HFD-fed mice. CONCLUSIONS: The findings highlight RNF31's essential role in the regulation of mitochondrial homeostasis in hepatocytes, emphasizing its potential as a therapeutic target for NAFLD.

Association of Launch Price and Clinical Value With Reimbursement Decisions for Anticancer Drugs in China.

BACKGROUND: To investigate the association of launch price and clinical value with reimbursement decisions for anticancer drugs after the implementation of reimbursement-linked price negotiation in China. METHODS: Anticancer drugs approved by the NMPA of China from January 2017 to June 2022 were eligible for inclusion. Approval and reimbursement dates of included drug indications were retrieved from publicly available resources. We collected measures of clinical value, including survival, quality of life, and overall response rate from pivotal clinical trials and calculated treatment price at launch. Univariate and multivariate Cox proportional hazards models were employed to estimate the association between launch price, clinical value, and reimbursement decisions of anticancer drugs in China. RESULTS: The median reimbursement lag was 579 days (IQR: 402 - 936) for 93 indications supported by randomized controlled trials and 637 days (IQR 373 - 858) for 42 indications supported by single-arm clinical trials. Reimbursement was granted to 60 (65%) and 23 (55%) indications supported by randomized controlled and single-arm clinical trials, respectively. The launch price of anticancer drugs was not associated with reimbursement decisions in multivariate regression analyses. Indications supported by randomized controlled trials with higher clinical value were more likely to be reimbursed (HR for survival=1.07, 95%CI: 1.00 -1.15, p = 0.037), while the overall response rate of indications supported by single-arm clinical trials was not associated with the likelihood of being reimbursed (HR = 2.09, 95%CI: 0.14 - 32.28, p = 0.595). CONCLUSION: The launch price of anticancer drugs may not have a significant impact on reimbursement decisions, while the implementation of reimbursement-linked price negotiation in China has prioritized anticancer drugs with higher clinical value, but only for indications supported by randomized controlled trials. Efforts are needed to prioritize indications supported by single-arm clinical trials that have higher value during the process of price negotiation.

TBHP/Et3N-Promoted Chemoselective Formylation and Peroxidation of Pyrrolo[2,1-a]isoquinolines.

An efficient formylation of pyrrolo[2,1-a]isoquinoline derivatives has been reached by the use of TBHP (tBuOOH) and Et3N as the mediator. In this strategy, CHO and CDO can be readily incorporated into heteroarenes by the utilization of CHCl3 and CDCl3 as the carbonyl sources. Interestingly, a solvent-controlled chemoselectivity was observed. The use of PhCl as a solvent resulted in dearomatization and peroxidation of pyrrolo[2,1-a]isoquinolines, delivering functionalized peroxides in 53-64% yields.

[Effects and mechanisms of negative air ions on blood pressure, oxidative stress and inflammation levels in SHR rats].

OBJECTIVE: To investigate the effects and possible mechanisms of negative air ions(NAIs) on blood pressure, oxidative stress, and inflammatory status in spontaneous hypertension rats(SHR). METHODS: A total of 60 SHR(half male and half female) were randomly divided into one-month and three-month groups, 30 rats per groups, based on the duration of the intervention. Each group was further randomized into three groups based on the daily intervention time: SHR control group, 2 h NAIs-SHR group, and 6 h NAIs-SHR group, 10 rats per groups. In addition, 20 Wistar Kyoto(WKY)(half male and half female), were randomized into one-month WKY group and three-month WKY group, 10 rats per groups, based on the intervention time. The 2 h NAIs-SHR group and 6 h NAIs-SHR group were exposed to an environment with NAIs concentrations of 4.5×10~4-5×10~4 cm~3 per day for 2 h and 6 h. The WKY group and SHR group were exposed to normal air on a daily basis. Blood pressure of rats in each group was measured every three days, while weight was measured once a week. After sacrificing the rats in the first month and the third month of rearing, wet weight of the organs was weighed. The enzyme linked immunosorbent assay(ELISA) was used to detect 8-hydroxylated deoxyguanosine(8-OHdG), interleukin-6(IL-6), interleukin-8(IL-8), tumor necrosis factor-α(TNF-α), nitric oxide(NO) and endothelin-1(ET-1) levels. Reactive oxygen species(ROS) detection kit was used to detect ROS level. Malondialdehyde(MDA) and superoxide dismutase(SOD), glutathione(GSH) and glutathione disulfide(GSSG) were measured by colorimetric analysis. HE staining was conducted to observe the histopathological morphological changes of the thoracic aorta in each group, and Western blot was conducted to detect the thoracic aortap38 mitogen-activated protein kinase(p38 MAPK), extracellular signal-regulated kinases(ERK), c-Jun n-terminal kinase(JNK), c-fos proteins, c-jun proteins and their phosphorylated proteins level. RESULTS: The weight of WKY male mice in the same week age group was higher than that of SHR control group, and there was no significant difference in the weight between the other groups. The coefficient of heart in SHR control group(4.66±0.48) was higher than that in WKY group(3.73±0.15)(P<0.05), while there were no significant differences in the coefficients of brain, kidney, liver and spleen among the groups. Blood pressure in WKY group at the same age was lower than that in SHR group, and blood pressure in SHR control group at 2-5 and 8-11 weeks was higher than that in 2 h NAIs-SHR and 6 h NAIs-SHR groups(P<0.05). HE staining showed that the internal, middle and external membranes of thoracic aorta in 2 h NAIs-SHR group and 6 h NAIs-SHR group were improved to varying degrees compared with those in SHR control group, including disordered internal membrane structure, thickened middle membrane and broken external membrane. In terms of oxidative stress levels, compared with the SHR control group, the ROS(0.66%±0.17%, 0.49%±0.32%) and 8-OHdG((48.29±8.00) ng/mL, (33.13±14.67)ng/mL) levels were lower in the 6 h NAIs-SHR group(P<0.05), while the GSH/GSSG ratio was higher in the one-month 6 h NAIs-SHR group(10.08±4.93). Compared with the 2 h NAIs-SHR group, the ROS level(0.99%±0.19%) was lower in the 6 h NAIs-SHR group(P<0.05). In terms of inflammatory factor levels, compared with the SHR control group, the IL-8 levels((160.44±56.54) ng/L, (145.77±38.39) ng/L) were lower in the 6 h NAIs-SHR group(P<0.05), while the ET-1 level((249.55±16.98) ng/L) was higher in the one-month WKY group. There was no significant difference in NO levels among the groups. The relative expression of p-p38 protein in the thoracic aorta of rats in the one-month SHR control group was lower than that in the WKY group(P<0.05). The relative expression of p-p38 and p-c-fos proteins in the thoracic aorta of rats at three-months was higher in the SHR control group than in the 2 h NAIs-SHR and 6 h NAIs-SHR groups(P<0.05). CONCLUSION: The intervention of NAIs at a concentration of 4.5×10~4-5×10~4/cm~3 may regulate the partial oxidation and inflammatory state of SHR rats through the ROS/MAPK/AP1 signaling pathway, thereby reducing their blood pressure level.

Fluorinated Polydopamine Shell Decorated Fillers in Polytetrafluoroethylene Composite for Achieving Highly Reduced Coefficient of Thermal Expansion.

The noticeable difference in the coefficient of thermal expansion (CTE) for polytetrafluoroethylene (PTFE) coatings and copper substrates is a major challenge for thermal debonding of the copper-clad laminate (CCL) in high-frequency communications. Theoretically, ceramic fillers with low CTEs in the coating can effectively reduce the gap, and there remains a trade-off between the dispersibility of fillers and the interfacial interactions with the polymeric matrix. Here, we propose a novel approach to prepare a pentafluorobenzoyl chloride (PFBC)-modified polydopamine (PDA) shell on silica particles by using amidation. Such modified particles perform excellent dispersion and exhibit diminished interfacial gaps in the PTFE matrix, which highly reduces CTE to 77 ppm/°C, accounting for only 48.1% of the neat coating. Moreover, the composite exhibits enhanced mechanical strength and toughness, and consequently suppresses thermal debonding in CCL under high-temperature conditions. Therefore, results present a promising potential for its use in the next-generation CCL of high-frequency communication devices.

Bacteroides and NAFLD: pathophysiology and therapy.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition observed globally, with the potential to progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Currently, the US Food and Drug Administration (FDA) has not approved any drugs for the treatment of NAFLD. NAFLD is characterized by histopathological abnormalities in the liver, such as lipid accumulation, steatosis, hepatic balloon degeneration, and inflammation. Dysbiosis of the gut microbiota and its metabolites significantly contribute to the initiation and advancement of NAFLD. Bacteroides, a potential probiotic, has shown strong potential in preventing the onset and progression of NAFLD. However, the precise mechanism by which Bacteroides treats NAFLD remains uncertain. In this review, we explore the current understanding of the role of Bacteroides and its metabolites in the treatment of NAFLD, focusing on their ability to reduce liver inflammation, mitigate hepatic steatosis, and enhance intestinal barrier function. Additionally, we summarize how Bacteroides alleviates pathological changes by restoring the metabolism, improving insulin resistance, regulating cytokines, and promoting tight-junctions. A deeper comprehension of the mechanisms through which Bacteroides is involved in the pathogenesis of NAFLD should aid the development of innovative drugs targeting NAFLD.

Identification of relevant differential genes to the divergent devel-opment of pectoral muscle in ducks by transcriptomic analysis.

Objective: The objective of this study was to identify candidate genes that play im-portant roles in skeletal muscle development in ducks. Methods: In this study, we investigated the transcriptional sequencing of embryonic pectoral muscles from two specialized line LCA and LCC ducks which were devel-oped from Liancheng White ducks (female) and Cherry Valley ducks (male) F6 hybrid population. In addition, prediction of target genes for the differentially expressed mRNAs was conducted and the enriched gene ontology (GO) terms and Kyoto En-cyclopedia of Genes and Genomes (KEGG) signaling pathways were further analyzed. Finally, a protein-to-protein interaction (PPI) network was analyzed by using the tar-get genes to gain insights into their potential functional association. Results: A total of 1428 differentially expressed genes (DEGs) with 762 being up-regulated genes and 666 being down-regulated genes in pectoral muscle of LCA and LCC ducks identified by RNA-seq (p < 0.05). Meanwhile, 23 GO terms in the down-regulated genes and 75 GO terms in up-regulated genes were significantly en-riched (p < 0.05). Furthermore, the top 5 most enriched pathways were ECM-receptor interaction, fatty acid degradation, pyruvate degradation, PPAR signaling pathway, and glycolysis/gluconeogenesis. Finally, the candidate genes including Integrin b3 (Itgb3), Pyruvate kinase M1/2 (Pkm), Insulin-like growth factor 1 (Igf1), glu-cose-6-phosphate isomerase（Gpi）, GABA type A receptor-associated protein-like 1(Gabarapl1), and Thyroid hormone receptor beta (Thrb) showed the most expression difference, and then were selected to verification by qRT-PCR. The result of qRT-PCR was consistent with that of transcriptome sequencing. Conclusion: This study provided information of molecular mechanisms underlying the developmental differences in skeletal muscles between specialized duck lines.

Decentralized Adaptive Secure Control of Uncertain Nonlinear Time-Varying Interconnected Systems Against Sensor and Actuator Attacks.

In this article, the decentralized adaptive secure control problem for cyber-physical systems (CPSs) against deception attacks is investigated. The CPSs are formed as a type of nonlinear interconnected strict-feedback systems with uncertain time-varying parameters. The attack affects the information transmission between sensor and actuator in a multiplicative manner. A novel decentralized adaptive backstepping secure control strategy is established by exploiting a particular kind of Nussbaum functions and a flat-zone Lyapunov function analysis approach. It is shown that all of closed-loop signals remain globally bounded, and each output signal eventually converges into a small neighborhood of the origin. Simulation results on an illustrative example are provided to display the effectiveness of the proposed control scheme.

Reliability and validity of a graphical computerized adaptive test Longshi scale for rapid assessment of activities of daily living in stroke survivors.

Stroke survivors frequently experience difficulties in daily activities, such as bathing, feeding, and mobility. This study aimed to evaluate the reliability and validity of a computer-adaptive test-Longshi scale (CAT-LS) for assessing activities of daily living (ADL) in stroke survivors. This cross-sectional study collected data using an electronic application. The ADL function of stroke survivors in rehabilitation departments of hospitals was assessed using both the CAT-LS and BI. Correlations between the CAT-LS and Barthel index (BI) and concurrent validity were evaluated using Pearson's correlation test and multiple linear regression. Interrater reliability was evaluated using the intraclass correlation coefficient based on a two-way random effect. The internal consistency of the CAT-LS was assessed using Cronbach's coefficient (α) and corrected item-total correlations. Overall, 103 medical institutions in China were used in this study. In total, 7151 patients with stroke were included in this study. The CAT-LS classified patients into three ADL groups (bedridden, domestic, and community) with significantly different BI scores (P < 0.05). The CAT-LS results obtained using the decision-tree scoring model were consistent with the scores for each BI item. A strong correlation was observed between CAT-LS and BI (Pearson's r: 0.6-0.894, P < 0.001). The CAT-LS demonstrated good internal consistency (Cronbach's α, 0.803-0.894) and interrater reliability (ICC, 0.928-0.979). CAT-LS is time-efficient and requires < 1 min to administer. The CAT-LS is a reliable and valid tool for assessing ADL function in stroke survivors and can provide rapid and accurate assessments that reduce the burden on healthcare professionals. Further validation of this tool in other populations and settings is necessary.Study registration number: No.: ChiCTR2000034067; http://www.chictr.org.cn/showproj.aspx?proj=54770 .

Comparison of temporomandibular joints in relation to ages and vertical facial types in skeletal class II female patients: a multiple-cross-sectional study.

BACKGROUND: The temporomandibular joint (TMJ) is closely related to the dynamic balance and stability of mandibular function and orthodontic treatment. Skeletal class II female patients are thought to be at high risk for TMJ disease. The relationship between the TMJ and craniofacial structures is still controversial. This study compared the morphology and position of the TMJ in skeletal class II adolescents and adults with various vertical facial types using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: A total of 117 skeletal class II patients were divided into three groups according to the FH-GoGn angle (hypodivergent, normodivergent and hyperdivergent), with 40 class I normodivergent patients serving as controls. Each group contained two age subgroups (adolescents: 11-14 years old, adults: 18-35 years old). The size (condylar length, height, long and short axis diameter, glenoid fossa width and depth) and shape (condylar neck inclination, condylar head angle and long axis angle, articular eminence inclination) of the condyle and fossa, joint space (anterior, superior, posterior, mesial and lateral), and position of the fossa (vertical, transverse, and anteroposterior distance) and condyle were measured and compared using CBCT. RESULTS: Class II hypodivergent patients exhibited the greatest condylar length, height, and long- and short-axis diameter; steepest articular eminence; deepest fossa depth; largest superior, mesial and lateral joint spaces; and highest fossa position in both age groups. The manifestations of class II hyperdivergent patients were mostly the opposite. In adults, except for the condylar long axis angle, the measurements of the condyle increased differently among skeletal patterns, while the measurements of the fossa decreased, as the joint spaces and fossa position remained approximately stable compared with those in adolescents. CONCLUSION: The vertical skeletal pattern, rather than the class II sagittal skeletal pattern, may be the main factor affecting the morphology and position of the TMJ. Attention should be given to the TMJ area in hyperdivergent patients with a relatively poor-fit condyle-fossa relationship. The changes in the TMJ with age were mainly morphological rather than positional and varied with skeletal pattern.

Chrysanthemum morifolium as a traditional herb: A review of historical development, classification, phytochemistry, pharmacology and application.

ETHNOPHARMACOLOGICAL RELEVANCE: In recent years, Chinese herbal medicine has gained more and more recognition in disease prevention and control due to its low toxicity and comprehensive treatment. C. morifolium (Chrysanthemum morifolium Ramat.), as the medicine food homology plant with the bioactivity of anti-oxidation, anti-inflammatory, neuroprotection and cardiovascular protection, has important therapeutic effects and health benefits for colds, inflammation, cardiovascular diseases and various chronic diseases. AIM OF THE STUDY: By reviewing the historical development, classification and distribution of germplasm resources, phytochemistry, pharmacology, and modern application of C. morifolium, the paper provides a reliable basis for the further research and application of chrysanthemum as therapeutic agents and functional additives. MATERIALS AND METHODS: The literature and information about C. morifolium published in the last ten years were collected from various platforms, including Google Scholar, PubMed, ScienceDirect, Web of Science and China Knowledge Network. RESULTS: A comprehensive analysis confirmed that C. morifolium originated in China, and it went through the development process from food and tea to medicine for more than 3000 years. During this period, different cultivars emerged through several breeding techniques and were distributed throughout the world. Moreover, A variety of chemical components such as flavonoids, phenolic acids, volatile oils, and terpenes in chrysanthemum have been proven they possess various pharmacology of anti-inflammatory, anti-oxidant, and prevention of chronic diseases by regulating inflammatory cytokines, oxidative stress responses and signaling pathways, which are the essential conditions to play a role in TCM, nutraceuticals and diet. CONCLUSION: This paper provides a comprehensive review of historical development, classification, phytochemistry, pharmacology, and modern application of C. morifolium. However, future studies should continue to focus on the bioactive compounds and the synergistic mechanism of the "multi-component, multi-target, and multi-pathway" of chrysanthemum, and it is necessary to develop more innovative products with therapeutic effects.

Deep learning assists detection of esophageal cancer and precursor lesions in a prospective, randomized controlled study.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

A semiparametric Gaussian mixture model for chest CT-based 3D blood vessel reconstruction.

Computed tomography (CT) has been a powerful diagnostic tool since its emergence in the 1970s. Using CT data, 3D structures of human internal organs and tissues, such as blood vessels, can be reconstructed using professional software. This 3D reconstruction is crucial for surgical operations and can serve as a vivid medical teaching example. However, traditional 3D reconstruction heavily relies on manual operations, which are time-consuming, subjective, and require substantial experience. To address this problem, we develop a novel semiparametric Gaussian mixture model tailored for the 3D reconstruction of blood vessels. This model extends the classical Gaussian mixture model by enabling nonparametric variations in the component-wise parameters of interest according to voxel positions. We develop a kernel-based expectation-maximization algorithm for estimating the model parameters, accompanied by a supporting asymptotic theory. Furthermore, we propose a novel regression method for optimal bandwidth selection. Compared to the conventional cross-validation-based (CV) method, the regression method outperforms the CV method in terms of computational and statistical efficiency. In application, this methodology facilitates the fully automated reconstruction of 3D blood vessel structures with remarkable accuracy.

Biosynthesis and Anticancer Activity of Genistein Glycoside Derivatives.

As a beneficial natural flavonoid, genistein has demonstrated a wide range of biological functions via regulating a number of targets and signaling pathways, such as anti-cancer, antioxidant, antibacterial, antiinflammatory, antifungal, antiviral, iron chelation, anti-obesity, anti-diabetes, and anti-hypertension. PubMed/Medline and Web of Science were searched using appropriate keywords until the end of December 2023. Despite its many potential benefits, genistein's clinical application is limited by low hydrophilicity, poor solubility, and suboptimal bioavailability due to its structure. These challenges can be addressed through the conversion of genistein into glycosides. Glycosylation of active small molecules may enhance their solubility, stability, and biological activity. In recent years, extensive research has been conducted on the synthesis, properties, and anticancer activity of glycoconjugates. Previous reviews were devoted to discussing the biological activities of genistin, with a little summary of the biosynthesis and the structure-activity relationship for their anticancer activity of genistein glycoside derivatives. Therefore, we summarized recent advances in the biosynthesis of genistein glycosylation and discussed the antitumor activities of genistein glycoside derivatives in a structure-activity relationship, which may provide important information for further development of genistein derivatives.

π-Extended Nonfullerene Acceptor for Compressed Molecular Packing in Organic Solar Cells To Achieve over 20% Efficiency.

Organic photovoltaics (OPVs) suffer from a trade-off between efficient charge transport and suppressed nonradiative recombination due to the aggregation-induced luminance quenching of organic semiconductors. To resolve this grand challenge, a π-extended nonfullerene acceptor (NFA) B6Cl with large voids among the honeycomb network is designed and introduced into photovoltaic systems. We find that the presence of a small amount of (i.e., 0.5 or 1 wt %) B6Cl can compress the molecular packing of the host acceptor L8-BO, leading to shortened π-π stacking distance from 3.59 to 3.50 Å (that will improve charge transport) together with ordered alkyl chain packing (that will inhibit nonradiative energy loss due to the suppressed C-C and C-H bonds vibrations), as validated by high-energy X-ray scattering measurements. This morphology transformation ultimately results in simultaneously improved JSC, FF, and VOC of OPVs. As a result, the maximum PCEs of PM6:L8-BO and D18:L8-BO are increased from 19.1 and 19.3% to 19.8 and 20.2%, respectively, which are among the highest values for single-junction OPVs. The university of B6Cl to increase the performance of OPVs is further evidenced in a range of polymer:NFA OPVs.

Near-Infrared Catalytic Chemiluminescence System based on Zinc Gallate Nanoprobe for Hydrazine Sensing.

To the deep tissue penetration and ultra-low background, developing near-infrared (NIR) chemiluminescence probes for human health and environmental safety has attracted more and more attention, but it remains a huge challenge. Herein, a novel NIR chemiluminescence (CL) system was rationally designed and developed, utilizing Cr3+-activated ZnGa2O4 (ZGC) nanoparticles as a catalytic luminophore via hypochlorite (NaClO) activation for poisonous target (hydrazine, N2H4) detection. With superior optical performance and unique catalytic structure of ZGC nanoparticles, the fabricated ZGC-NaClO-N2H4 CL system successfully demonstrated excellent NIR emission centered at 700 nm, fast response, and high sensibility (limit of detection down to 0.0126 µM). Further experimental studies and theoretical calculations found the cooperative catalytic chemiluminescence resonance energy transfer mechanism in the ZGC-NaClO-N2H4 system. Remarkably, the ZGC-based NIR CL system was further employed for N2H4 detection in a complicated matrix involving bioimaging and real water samples, thereby opening a new way as a highly reliable and accurate tool in biomedical and environmental monitoring applications.