Tolerogenic dendritic cells alleviate collagen-induced arthritis by regulating T-cell differentiation and inhibiting NLRP3-mediated apoptosis.

OBJECTIVE: Tolerogenic dendritic cells (tolDCs) have emerged as a potential treatment for rheumatoid arthritis (RA). However, the detailed mechanism requires further investigation. In this study, we aimed to explore the effects of tolDCs on T-cell differentiation and NLRP3-mediated pyroptosis in a collagen-induced arthritis (CIA) rat model. METHODS: TolDCs were induced using NF-κB ODN decoy. The efficacy of tolDCs intervention in alleviating arthritis symptoms was evaluated in CIA rats. Flow cytometry was employed to analyze CD4+ T-cell subpopulations, while scanning electron microscopy was utilized to observe pyroptosis morphology. Immunohistochemistry was used to assess the expression of pyroptosis-associated proteins. RESULTS: TolDCs intervention significantly reduced joint inflammation and damage in CIA rats. Moreover, it successfully restored the balance of Th1/Th2 cells as well as the balance of Treg/Th17 cells. Furthermore, tolDCs intervention effectively suppressed NLRP3-mediated pyroptosis in the synovium, decreasing the release of IL-1ß and IL-18. CONCLUSION: Our findings underscore the efficacy of tolDCs in attenuating CIA progression through modulation of CD4+ T-cell subpopulations and inhibition of NLRP3-mediated pyroptosis.

Anisotropic Strain-Tailoring Nonlinear Optical Response in van der Waals NbOI2.

Two-dimensional (2D) NbOI2 demonstrates significant second-harmonic generation (SHG) with a high conversion efficiency. To unlock its full potential in practical applications, it is desirable to modulate the SHG behavior while utilizing the intrinsic lattice anisotropy. Here, we demonstrate direction-specific modulation of the SHG response in NbOI2 by applying anisotropic strain with respect to the intrinsic lattice orientations, where more than 2-fold enhancement in the SHG intensity is achieved under strain along the polar axis. The strain-driven SHG evolution is attributed to the strengthened built-in piezoelectric field (polar axis) and the enlarged Peierls distortions (nonpolar axis). Moreover, we provide quantifications of the correlation between strain and SHG intensity in terms of the susceptibility tensor. Our results demonstrate the effective coupling of orientation-specific strain to the anisotropic SHG response through the intrinsic polar order in 2D nonlinear optical crystals, opening a new paradigm toward the development of functional devices.

Predictors of amputation in patients with diabetic foot ulcers: a multi-centre retrospective cohort study.

PURPOSE: Investigating risk factors for amputation in patients with diabetic foot ulcer (DFU) and developing a nomogram prediction model. METHODS: We gathered case data of DFU patients from five medical institutions in Anhui Province, China. Following eligibility criteria, a retrospective case-control study was performed on data from 526 patients. RESULTS: Among the 526 patients (mean age: 63.32 ± 12.14), 179 were female, and 347 were male; 264 underwent amputation. Univariate analysis identified several predictors for amputation, including Blood type-B, Ambulation, history of amputation (Hx. Of amputation), Bacterial culture-positive, Wagner grade, peripheral arterial disease (PAD), and laboratory parameters (HbA1c, Hb, CRP, ALB, FIB, PLT, Protein). In the multivariate regression, six variables emerged as independent predictors: Blood type-B (OR = 2.332, 95%CI [1.488-3.657], p < 0.001), Hx. Of amputation (2.298 [1.348-3.917], p = 0.002), Bacterial culture-positive (2.490 [1.618-3.830], p <0.001), Wagner 3 (1.787 [1.049-3.046], p = 0.033), Wagner 4-5 (4.272 [2.444-7.468], p <0.001), PAD (1.554 [1.030-2.345], p = 0.036). We developed a nomogram prediction model utilizing the aforementioned independent risk factors. The model demonstrated a favorable predictive ability for amputation risk, as evidenced by its area under the receiver operating characteristics (ROC) curve of 0.756 and the well-fitted corrected nomogram calibration curve. CONCLUSION: Our findings underscore Blood type-B, Hx. Of amputation, Bacterial culture-positive, Wagner 3-5, and PAD as independent risk factors for amputation in DFU patients. The resultant nomogram exhibits substantial accuracy in predicting amputation occurrence. Timely identification of these risk factors can reduce DFU-related amputation rates.

Progression rate of radiation-induced carotid stenosis in head and neck cancer survivors after statin treatment: a retrospective cohort study.

BACKGROUND AND AIMS: Whether statin treatment is effective in retarding the progression of radiation-induced carotid stenosis (RICS) in head and neck cancer (HNC) survivors has not been well studied. The purpose of this study was to assess the association of statin treatment with RICS progression rate in HNC survivors after radiotherapy. METHODS: We conducted a retrospective cohort study at Sun Yat-sen Memorial Hospital, Sun Yat-sen University in Guangzhou, China. Between January 2010 and December 2021, we screened HNC survivors whose carotid ultrasound scans had shown stenosis of the common and/or internal carotid arteries. The primary outcome was the RICS progression rate. We compared eligible patients treated with statins with those who did not in multivariable Cox regression models. RESULTS: A total of 200 patients were included in this study, of whom 108 received statin treatment and 92 did not. Over a mean follow-up time of 1.5 years, 56 (28.0%) patients showed RICS progression, 24 (42.9%) and 32 (57.1%) in the statin and control groups, respectively. The statin group showed less RICS progression than the control group (adjusted-HR 0.49, 95% CI 0.30-0.80, P = 0.005). In the subgroup analysis, there was no significant interaction in the effect of statins on lowering RICS progression rate in the subgroups stratified by baseline low-density lipoprotein cholesterol (LDL-C) levels (P for interaction = 0.53) or baseline degrees of stenosis (P for interaction = 0.50). CONCLUSIONS: Statin treatment was associated with a lower risk of RICS progression in patients with HNC after radiotherapy, regardless of baseline LDL-C level and baseline stenosis degrees.

Brown Adipose Tissue Promotes Autologous Fat Grafts Retention Possibly Through Inhibiting Wnt/ß-Catenin Pathway.

BACKGROUND: In plastic surgery, autologous fat grafts (AFG) play an important role because of their abundant supply, biocompatibility, and low rejection rate. However, the lower retention rate of fat grafts limits their widespread use. Brown adipose tissue (BAT) can promote angiogenesis and regulate the level of associated inflammation. This study explored whether BAT has a facilitative effect on fat graft retention. METHODS: We obtained white adipose tissue (WAT) from c57 mice and combined it with either BAT from c57 mice or phosphate-buffered saline (PBS) as a control. These mixtures were injected subcutaneously into the back of thymus-free nude mice. After 12 weeks, fat grafts were harvested, weighed, and analyzed. RESULTS: We found that the BAT-grafted group had higher mass retention, more mature adipocytes, and higher vascularity than the other group. Further analysis revealed that BAT inhibited M1 macrophages; down-regulated IL-6, IL-1ß, and TNF-ß; upregulated M2 macrophages and Vascular endothelial growth factor-A (VEGFA); and promoted adipocyte regeneration by inhibiting the Wnt/ß-catenin pathway, which together promoted adipose graft retention. CONCLUSION: The study demonstrated that BAT improved adipose graft retention by promoting angiogenesis, inhibiting tissue inflammation levels and the Wnt/ß-catenin pathway. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Blockage of VEGF function by bevacizumab alleviates early-stage cerebrovascular dysfunction and improves cognitive function in a mouse model of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder and the predominant type of dementia worldwide. It is characterized by the progressive and irreversible decline of cognitive functions. In addition to the pathological beta-amyloid (Aß) deposition, glial activation, and neuronal injury in the postmortem brains of AD patients, increasing evidence suggests that the often overlooked vascular dysfunction is an important early event in AD pathophysiology. Vascular endothelial growth factor (VEGF) plays a critical role in regulating physiological functions and pathological changes in blood vessels, but whether VEGF is involved in the early stage of vascular pathology in AD remains unclear. METHODS: We used an antiangiogenic agent for clinical cancer treatment, the humanized monoclonal anti-VEGF antibody bevacizumab, to block VEGF binding to its receptors in the 5×FAD mouse model at an early age. After treatment, memory performance was evaluated by a novel object recognition test, and cerebral vascular permeability and perfusion were examined by an Evans blue assay and blood flow scanning imaging analysis. Immunofluorescence staining was used to measure glial activation and Aß deposits. VEGF and its receptors were analyzed by enzyme-linked immunosorbent assay and immunoblotting. RNA sequencing was performed to elucidate bevacizumab-associated transcriptional signatures in the hippocampus of 5×FAD mice. RESULTS: Bevacizumab treatment administered from 4 months of age dramatically improved cerebrovascular functions, reduced glial activation, and restored long-term memory in both sexes of 5×FAD mice. Notably, a sex-specific change in different VEGF receptors was identified in the cortex and hippocampus of 5×FAD mice. Soluble VEGFR1 was decreased in female mice, while full-length VEGFR2 was increased in male mice. Bevacizumab treatment reversed the altered expression of receptors to be comparable to the level in the wild-type mice. Gene Set Enrichment Analysis of transcriptomic changes revealed that bevacizumab effectively reversed the changes in the gene sets associated with blood-brain barrier integrity and vascular smooth muscle contraction in 5×FAD mice. CONCLUSIONS: Our study demonstrated the mechanistic roles of VEGF at the early stage of amyloidopathy and the protective effects of bevacizumab on cerebrovascular function and memory performance in 5×FAD mice. These findings also suggest the therapeutic potential of bevacizumab for the early intervention of AD.

Biomarkers of peripheral blood neutrophil extracellular traps in the diagnosis and progression of malignant tumors.

BACKGROUND AND AIMS: The mortality rate associated with malignant tumors remains high and there is a lack of effective diagnostic and tumor progression markers. Neutrophil extracellular traps (NETs) can promote tumor-associated thrombosis, invasive metastasis, and inflammatory responses, but there is a lack of research on the value of measuring NETs in the peripheral blood of patients with malignancies. METHODS: We included 263 patients with malignancies (55 gliomas, 101 ovarian, 64 colorectal, and 43 lung cancers) and 75 healthy controls in this study. We compared the levels of citrullinated histone H3 (citH3), cell-free DNA (cfDNA), and systemic inflammation-related parameters, including neutrophils, lymphocytes, monocytes, platelets, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune inflammation index, and systemic inflammation response index. We assessed the value of changes in NETs in peripheral blood to determine the diagnosis, venous thromboembolism, clinical staging, and systemic inflammatory response in patients with malignancy. RESULTS: The levels of citH3 and cfDNA in peripheral blood can distinguish between healthy controls and tumor patients. The levels of citH3 and cfDNA before clinical intervention did not predict the risk of combined venous thromboembolism in oncology patients in the short-term after clinical intervention. The levels of citH3, cfDNA, and systemic inflammation-related parameters in the peripheral blood of tumor patients increased with the clinical stage. There was a correlation between cfDNA levels in peripheral blood and systemic inflammation-related parameters in tumor patients, and this correlation was more significant in patients with advanced tumors. CONCLUSIONS: Changes in NETs in the peripheral blood differ between healthy controls and patients with malignant tumors. NETs may be involved in tumor-induced systemic inflammatory responses through interaction with circulating inflammatory cells, thus promoting tumor progression. NETs may be used as markers to assist in the diagnosis and progression of tumor malignancy.

Tibetan medicine Ruyi Zhenbao Pill ameliorates neuropathic pain by inhibiting the CXCL10-CXCR3 pathway in spinal cord of spinal nerve ligation model.

ETHNOPHARMACOLOGICAL RELEVANCE: Ruyi Zhenbao Pill (RYZBP) is a traditional Tibetan medicine that has been used for over 300 years in China to treat neurological diseases, specifically neuropathic pain (NP). However, its characteristics and mechanism of action in treating NP remains unclear. AIM OF THE STUDY: Based on animal experiments and transcriptomics to evaluate the characteristics and mechanism of RYZBP in treating NP. METHODS: Mice were divided into six groups using random assignment: sham-operation group, spinal nerve ligation (SNL) group, RYZBP low (0.65 g kg-1), medium (1.30 g kg-1), high (2.60 g kg-1) doses groups, and positive drug pregabalin (PGB, 0.05 g kg-1) group. Mice received intragastrical administered for 14 consecutive days. SNL and intrathecal injection models were employed. The analgesic effects were assessed using the Von Frey test, Acetone test, and Hot Plate test. L5 spinal dorsal horns were collected for transcriptomics on day 15. The potential signaling pathways and Hub genes of RYZBP to ameliorate NP were obtained through transcriptomics and network pharmacology. Molecular docking was utilized to evaluate the binding ability of candidate active ingredients with the Hub genes. Finally, western blot (WB) and immunofluorescence (IF) were used to validate the predicted targets. RESULTS: RYZBP demonstrated a dose-dependent alleviation of mechanical allodynia, cold and heat stimulus-induced pain in SNL mice. Transcriptomics analysis identified 24 differentially expressed genes, and pathway enrichment analysis revealed that the CXCL10-CXCR3 signal axis may be the primary biological pathway through which RYZBP relieve NP. Molecular docking test indicated that the active ingredient in RYZBP exhibit a strong affinity for the target protein CXCL10. WB and IF tests showed that RYZBP can significantly inhibit CXCL10 and CXCR3 and its downstream molecules expression in the spinal dorsal horn of SNL mice. Additionally, intrathecal injection of rmCXCL10 worsened pain hypersensitivity, while RYZBP was able to suppress the pain hypersensitivity response induced by rmCXCL10 and reduce the expression levels of CXCL10 and CXCR3 and its downstream molecules. CONCLUSION: RYZBP had a significant analgesic effect on NP model, and this effect may be related to inhibiting the CXCL10-CXCR3 pathway in the spinal dorsal horn.

Progression of cognitive dysfunction in NPC survivors with radiation-induced brain necrosis: A prospective cohort.

BACKGROUND AND PURPOSE: The evidence of longitudinal changes in cognition in nasopharyngeal carcinoma (NPC) survivors with radiation-induced brain necrosis (RIBN) after radiotherapy (RT) remained insufficient. We aimed to estimate the clinical progression rate of cognitive decline and identify patients with differential decline rates. MATERIALS AND METHODS: Based on an ongoing prospective cohort study, NPC patients aged ≥18 years old and diagnosed with RIBN were included in this current analysis if they finished the time frame of 3-year follow-up and had at least twice cognition assessments. The Chinese version of the Montreal Cognitive Assessment (MoCA) was used to assess the cognitive state. Linear mixed-effect models were used to analyze the annual progression rates of MoCA total and seven sub-items scores. RESULTS: Among 134 patients in this study, the transition probability from normal to mild/moderate cognitive dysfunction were 14.2 % (19/134) and 1.49 % (2/134) respectively during the median follow-up time of 2.35 years. The total MoCA score declined by -0.569 (SE 0.208) points annually (p = 0.008). Patients with ≤6 years of duration from RT to RIBN have higher annual progression rate of total scores [-0.851 (SE 0.321), p = 0.013; p for interaction = 0.041]. CONCLUSION: Our findings of the annual decline rate of cognition in NPC patients with RIBN from a 3-year longitudinal data, particularly for those who developed RIBN rapidly after RT, have important implications for the upcoming clinical trials designed to prevent or decrease cognitive decline in NPC patients with RIBN, regarding the selection of study patients and the calculation of sample size.

Target-Based Design, Synthesis, and Biological Evaluation of Novel 1,2,4-Triazolone Derivatives as Potential nAChR Modulators.

Novel agrochemicals have been successfully developed using target-based drug design (TBDD). To discover a novel, efficient, and highly selective nicotinic insecticide candidate, we developed a unified pharmacological model using TBDD by studying the binding modes of 11 nicotinic acetylcholine receptor (nAChR) modulators with acetylcholine binding protein (AChBP) targets for the first time. This model was used to design and develop a series of 1,2,4-triazolone derivatives. Bioassays demonstrated excellent insecticidal activities against Aphis glycines of compounds 4k (LC50 = 4.95 mg/L) and 4q (LC50 = 3.17 mg/L), and low toxicities to Apis mellifera. Additionally, compound 4q was stably bound to Aplysia californica AChBP, which was consistent with the pharmacological model obtained via molecular docking and molecular dynamics simulations. Therefore, compound 4q could be a potential lead candidate targeting nAChR. The explicit pharmacological model of nAChR modulators with Ac-AChBP in this study may facilitate the future rational design of eco-friendly nicotinic insecticides.

Precise Regulation of Juvenile Hormone III R-Stereoisomer Synthesis by Apis mellifera through Specifically Binding Methyl-(2E,6E)-farnesoate and Strictly Controlling Its Titer.

Juvenile hormone III (JH III) is a crucial hormone synthesized exclusively as R-stereoisomer in most insects. Herein, we established a mature Tris-HCl culture system for essential biochemical reactions and applied stable instrumental detection methods to analyze JH III, methyl farnesoate (MF) and juvenile hormone acid (JHA) using UPLC-MS/MS. Our results revealed that the R-JH III terminal synthesis pathway in Apis mellifera follows the "esterify then epoxidize" sequence, with precise methyl-(2E,6E)-farnesoate titer regulation and its spatial cis-trans isomerism, achieving selective R-JH III synthesis. Furthermore, we observed that the preferred generation of S/R-JH III chiral enantiomers varied depending on the spatial cis-trans isomerism of different MFs. Our results suggest that S-JH III could theoretically exist in insects, offering a novel perspective for understanding the synthesis mechanism of diverse complex juvenile hormones in different insect species.

A short neuropeptide F analog (sNPF), III-2 may particularly regulate juvenile hormone III to influence Spodoptera frugiperda metamorphosis and development.

Allatostatin (AS) or Allatotropin (AT) is a class of insect short neuropeptide F (sNPF) that affects insect growth and development by inhibiting or promote the synthesis of juvenile hormone (JH) in different insects. III-2 is a novel sNPF analog derived from a group of nitroaromatic groups connected by different amino acids. In this study, we found that III-2 showed high insecticidal activity against S. frugiperda larvae with a LC50 of 18.7 mg L-1. As demonstrated by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), III-2 particularly facilitated JH III and hindered 20E synthesis in S. frugiperda. The results of RNA-Seq and quantitative real-time polymerase chain reaction (qPCR) showed that III-2 treatment promoted the expression of key genes such as SfCYP15C1 in JH synthesis pathway and inhibited the expression of SfCYP314A1 and other genes in the 20E synthetic pathway. Significant differences were also observed in the expression of the genes related to cuticle formation. We report for the first time that sNPF compounds specifically interfere with the synthesis and secretion of a certain JH in insects, thus affecting the ecdysis and growth of insects, and leading to death. This study may provide a new plant conservation concept for us to seek the targeted control of certain insects based on specific interference with different JH.

S-dinotefuran affects the social behavior of honeybees (Apis mellifera)and increases their risk in the colony.

The toxic effects of neonicotinoid pesticides on honeybees is a global concern, whereas little is known about the effect of stereoisomeric pesticides among honeybee social behavior. In this study, we investigated the effects of stereoisomeric dinotefuran on honeybee social behavior. We found that honeybees exhibit a preference for consuming food containing S-dinotefuran, actively engage in trophallaxis with S-dinotefuran-consuming peers, and consequently acquire higher levels of S-dinotefuran compared with R-dinotefuran. In comparison to R-dinotefuran, S-dinotefuran stimulates honeybees to elevate their body temperature, thereby attracting more peers for trophallaxis. Transcriptome analysis revealed a significant enrichment of thermogenesis pathways due to S-dinotefuran exposure. Additionally, metabolome data indicated that S-dinotefuran may enhance body temperature by promoting lipid synthesis in the lysine degradation pathway. Consequently, body temperature emerges as a key factor influencing honeybee social behavior. Our study is the first to highlight the propensity of S-dinotefuran to raise honeybee body temperature, which prompts honeybee to preferentially engage in trophallaxis with peers exhibiting higher body temperatures. This preference may lead honeybees to collect more dinotefuran-contaminated food in the wild, significantly accelerating dinotefuran transmission within a population. Proactive trophallaxis further amplifies the risk of neonicotinoid pesticide transmission within a population, making honeybees that have consumed S-dinotefuran particularly favored within their colonies. These findings may contribute to our understanding of the higher risk associated with neonicotinoid use compared with other pesticides.

Efficacy of transcutaneous auricular vagus nerve stimulation on radiotherapy-related neuropathic pain in patients with head and neck cancers (RELAX): protocol for a multicentre, randomised, double-blind, sham-controlled trial.

INTRODUCTION: Radiotherapy-related neuropathic pain (RRNP) is one of the most distressing complications after radiotherapy for head and neck cancers. Drug therapy is not sufficiently effective and has limitations in terms of dose titration period and side effects. Transcutaneous auricular vagus nerve stimulation (taVNS), which stimulates the auricular branches of the vagus nerve through electrical impulses, has been proven to have analgesic effects in certain diseases. However, it is unknown whether taVNS can relieve RRNP. METHODS AND ANALYSIS: This is a multicentre, randomised, double-blind, parallel, sham-controlled trial. We will include adult patients newly diagnosed with neuropathic pain after radiotherapy for head and neck cancers. One hundred and sixteen individuals will be recruited and randomly assigned in a 1:1 ratio to receive taVNS or sham stimulation. The interventions will last for 7 days, twice daily for 30 min each. The primary efficacy outcome is pain reduction on day 7. The secondary outcomes are changes in functional interference, psychological distress, fatigue, quality of life and serum inflammatory factors. The study may provide a new early intervention strategy for RRNP among patients with head and neck cancers. ETHICS AND DISSEMINATION: This study has been approved by the Medical Research Ethics Committee of Sun Yat-sen University (SYSKY-2022-109-01) and will be conducted in strict accordance with the Declaration of Helsinki. Ethical approvals will be obtained separately for all centres involved in the study. Study results will be published in peer-reviewed academic journals. The database of the study will be available from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: NCT05543239.

Different types of milk consumption and the risk of dementia: Analysis from a large-scale cohort study.

BACKGROUND & AIMS: Previous studies have investigated whether milk consumption has a role in preventing the development of cognitive impairment, but the results were inconsistent. Importantly, most of them have disregarded the role of different types of milk. This study aimed to examine the associations between different types of milk consumption and the risk of dementia. METHODS: In this large-scale cohort study, participants without cognitive impairment at baseline were included from the UK Biobank. The type of milk mainly used was self-reported at baseline, including full-cream milk, skimmed-milk, soy milk, other milk, and no milk. The primary outcome was all-cause dementia. Secondary outcomes included Alzheimer's disease and vascular dementia. RESULTS: Of the 307,271 participants included in the study (mean age 56.3 [SD 8.1] years), 3789 (1.2%) incident all-cause dementia cases were observed over a median follow-up of 12.3 years. After adjustment for potential confounders, only soy milk consumers had a statistically significantly lower risk of all-cause dementia compared with no milk consumers (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.54 to 0.90). When compared with soy milk non-consumers consisting of full-cream milk, skimmed-milk, and other milk consumers, soy milk consumers still showed a lower risk of all-cause dementia (HR, 0.76; 95% CI, 0.63 to 0.92), and there was no significant interaction with genetic risk for dementia (P for interaction = 0.15). Soy milk consumers showed a lower risk of Alzheimer's disease (HR, 0.70; 95% CI, 0.51 to 0.94; P = 0.02), while the association was not significant for vascular dementia (HR, 0.72; 95% CI, 0.47 to 1.12; P = 0.14). CONCLUSIONS: The main consumption of soy milk was associated with a lower risk of dementia, particularly non-vascular dementia. Additional studies are needed to investigate how this association varies with the dose or frequency of the consumption of soy milk and to examine the generalizability of these findings in different populations.

Study on the Application of Concentrated Growth Factor Combined With Adipose Transplantation in Repairing Depressed Deformities of Soft Tissue in the Face.

BACKGROUND: Autologous fat is a rich source of adipose tissue that is safe for transplantation. Decreasing the long-term absorption rate is key to improve the survival of transplanted adipose tissue. The aim of this study was to assess the effect of concentrated growth factor (CGF) on the survival of transplanted adipose tissue for repair of facial depression malformations. METHODS: Coleman adipose granules (CAGs) were prepared from venous blood. In the animal experiment, the ears of 30 healthy male New Zealand white rabbits were randomly allocated to 1 of 4 groups: CGF + CAG (CGF group), platelet-rich fibrin (PRF) + CAG (PRF group), CAG alone (CAG group), and adipose granule transplantation group (control group). Postoperative survival of the transplanted adipose tissue was assessed, the survival and absorption rates of adipose were calculated, and immunohistochemical analysis of specimens was conducted by staining with hematoxylin and eosin and Oil Red O. Of 43 outpatients, 22 received simple adipose transplantation and 21 received autologous CGF combined with adipose transplantation. The adipose absorption rate, complication rate, and cosmetic improvement of the 2 groups were compared. RESULTS: More adipocytes that are normal were observed in the CGF group, with fewer vacuoles and more uniform distribution of adipose tissue. Survival of the adipose tissue was superior in the CGF and PRF groups. Meanwhile, vascular density and long-term stability were better in the CGF group than the PRF group. In terms of clinical efficacy, the uniformity and survival rate of the adipose tissue were relatively improved in the CGF group compared with the simple adipose particle transplantation group, with less early liquefaction. CONCLUSION: Concentrated growth factor stabilized and improved the survival of transplanted adipose tissue for filling of facial depression malformations.

Association of earlier age at menopause with risk of incident dementia, brain structural indices and the potential mediators: a prospective community-based cohort study.

Background: To date, there is no homogeneous evidence of whether earlier age at menopause is associated with incident dementia. In addition, the underlying mechanism and driven mediators are largely unknown. We aimed to fill these knowledge gaps. Methods: This community-based cohort study included 154,549 postmenopausal women without dementia at enrolment (between 2006 and 2010) from the UK Biobank who were followed up until June 2021. We followed up until June 2021. Age at menopause was entered as a categorical variable (<40, 40-49, and ≥50 years) with ≥50 years taken as a reference. The primary outcome was all-cause dementia in a time-to-event analysis and the secondary outcomes included Alzheimer's disease, vascular dementia, and other types of dementia. In addition, we investigated the association between magnetic resonance (MR) brain structure indices with earlier menopause, and explored the potential underlying driven mediators on the relationship between earlier menopause and dementia. Findings: 2266 (1.47%) dementia cases were observed over a median follow-up period of 12.3 years. After adjusting for confounders, women with earlier menopause showed a higher risk of all-cause dementia compared with those ≥50 years (adjusted-HRs [95% CIs]: 1.21 [1.09-1.34] and 1.71 [1.38-2.11] in the 40-49 years and <40 years groups, respectively; P for trend <0.001). No significant interactions between earlier menopause and polygenic risk score, cardiometabolic factors, type of menopause, or hormone-replacement therapy strata were found. Earlier menopause was negatively associated with brain MR global and regional grey matter indices, and positively associated with white matter hyperintensity. The relationship between earlier menopause and dementia was partially mediated by menopause-related comorbidities including sleep disturbance, mental health disorder, frailty, chronic pain, and metabolic syndrome, with the proportion (95% CI) of mediation effect being 3.35% (2.18-5.40), 1.38% (1.05-3.20), 5.23% (3.12-7.83), 3.64% (2.88-5.62) and 3.01% (2.29-4.40), respectively. Multiple mediator analysis showed a combined effect being 13.21% (11.11-18.20). Interpretation: Earlier age at menopause was associated with risk of incident dementia and deteriorating brain health. Further studies are warranted to clarify the underlying mechanisms by which earlier age at menopause is linked to an increased risk of dementia, and to determine public health strategies to attenuate this association. Funding: National Natural Science Foundation of China, the Science and Technology Program of Guangzhou, the Key Area Research and Development Program of Guangdong Province, the China Postdoctoral Science Foundation, and the Guangdong Basic and Applied Basic Research Foundation.

Simultaneous Detection and Distribution of Five Juvenile Hormones in 58 Insect Species and the Absolute Configuration in 32 Insect Species.

Juvenile hormone (JH) plays an important role in regulating various insect physiological processes. Herein, a novel method (chiral and achiral) for the simultaneous detection of five JHs was established by processing a whole insect without complicated hemolymph extraction. The proposed method was used to determine the distribution of JHs in 58 insect species and the absolute configuration of JHs in 32 species. The results showed that JHSB3 was uniquely synthesized in Hemiptera, JHB3 was unique to Diptera, and JH I and JH II were unique to Lepidoptera. JH III was present in most insect species surveyed, with social insects having generally higher JH III titers. Interestingly, JHSB3 and JHB3, both double epoxidation JHs, were found in insects with sucking mouthparts. The absolute conformation of JH III and the 10C of the detected JHs were all R stereoisomers.

Prognostic Value of Nutritional Assessments on Overall Survival in Head and Neck Cancer Survivors with Radiation-Induced Brain Necrosis.

Malnutrition is related to worsened prognosis, but the association between nutritional risk status and overall survival in radiation-induced brain necrosis (RN) has never been studied. We included consecutive patients who had received radiotherapy for head and neck cancer (HNC) and subsequently developed RN from 8 January 2005 through to 19 January 2020. The primary outcome was overall survival. We utilized three commonly-used nutritional assessments: the Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and the COntrolling NUTritional Status (CONUT) measure, to quantify the baseline nutritional risk. A total of 398 eligible patients were included. During a median follow-up of 2.3 years, 42 (10.6%) patients died of any cause. Malnutrition at admission was associated with an increased risk of future death, as assessed by the GNRI (per 1-point decreased, HR 1.05, 95%CI 1.02-1.09, p = 0.001), the PNI (per 1-point decreased, HR 1.07, 95%CI 1.03-1.12, p = 0.002), and the CONUT (per 1-point increased, HR 1.22, 95%CI 1.08-1.37, p = 0.001). There were no nonlinear correlations between all three indices and post-RN survival. Among HNC survivors with RN, the assessment of nutritional risk by composite indices upon admission could help identify patients who might be at high risk of future death and deliver better nutritional management.

Association of the awareness of the epidemic, mental health status with mobile phone screen use time in Chinese college students during COVID-19 isolation and control.

OBJECTIVE: This study aimed to investigate the awareness of the epidemic among college students and their mental health as well as to explore the association between their awareness of the epidemic mental health and the daily mobile phone screen use time, in order to provide guidance for the publicity of school epidemic prevention and control knowledge and the psychological counseling of students. METHODS: A cross-sectional design was employed among 780 college students, The Pandemic Fatigue Questionnaire, epidemic prevention and control knowledge and the mental health Scale were used to collect data through an online survey. RESULTS: 1. Awareness rate of the transmission routes and protective measures of COVID-19 among college students is higher when the daily mobile screen use time is 3-7 hours. 2. 21.79% of the 780 college students felt stressed; 24.87% felt anxious; 19.23% showed depression. 3. The scores of each subscale in the daily mobile phone screen use time of 3-7 hours and more than 7 hours were higher, and the scores of each subscale in the group of more than 7 hours were the highest. Further correlation analysis found that the time spent on mobile phone screens was positively correlated with stress, anxiety, and depression scores (r = 0.155, 0.180, 0.182, P<0.01). CONCLUSION: During the COVID-19 isolation and control period, college students with different mobile screen usage time have different understandings of the epidemic. Long-term mobile screen use is related to the occurrence of psychological problems such as stress, anxiety, and depression. Therefore, education departments and schools should pay attention to college students' mobile phone use time to reduce the occurrence of bad psychological state of students.