A novel anti-LAG-3/TIGIT bispecific antibody exhibits potent anti-tumor efficacy in mouse models as monotherapy or in combination with PD-1 antibody.

We report the generation of a novel anti-LAG-3/TIGIT bispecific IgG4 antibody, ZGGS15, and evaluated its anti-tumor efficacy in mouse models as monotherapy or in combination with a PD-1 antibody. ZGGS15 exhibited strong affinities for human LAG-3 and TIGIT, with KDs of 3.05 nM and 2.65 nM, respectively. ZGGS15 has EC50s of 0.69 nM and 1.87 nM for binding to human LAG-3 and TIGIT on CHO-K1 cells, respectively. ZGGS15 competitively inhibited the binding of LAG-3 to MHC-II (IC50 = 0.77 nM) and the binding of TIGIT to CD155 (IC50 = 0.24 nM). ZGGS15 does not induce ADCC, CDC, or obvious cytokine production. In vivo results showed that ZGGS15 had better anti-tumor inhibition than single anti-LAG-3 or anti-TIGIT agents and demonstrated a synergistic effect when combined with nivolumab, with a significantly higher tumor growth inhibition of 95.80% (p = 0.001). The tumor volume inhibition rate for ZGGS15 at 2 mg/kg was 69.70%, and for ZGGS15 at 5 mg/kg plus nivolumab at 1 mg/kg, it was 94.03% (p < 0.001). Our data reveal that ZGGS15 exhibits potent anti-tumor efficacy without eliciting ADCC or CDC or causing cytokine production, therefore having a safe profile.

The effects of exosomes originating from different cell sources on the differentiation of bone marrow mesenchymal stem cells into schwann cells.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can differentiate into Schwann cells (SCs) during peripheral nerve injury; in our previous research, we showed that SC-derived exosomes (SC-exos) played a direct induction role while fibroblast-derived exosomes (Fb-exos) had no obvious induction role. The induction role of neural stem cell (NSC)-derived exosomes (NSC-exos) has also been widely confirmed. However, no studies have compared the induction effects of these three types of cells at the same time. Therefore, by investigating the effect of these three cell-derived exosomes upon the induction of BMSCs to differentiate into SCs, this study explored the role of different exosomes in promoting the differentiation of stem cells into SCs cells, and conducted a comparison between the two groups by RNA sequencing to further narrow the range of target genes and related gene pathways in order to study their related mechanisms. MATERIALS AND METHODS: We extracted exosomes from SCs, fibroblasts (Fb) and neural stem cells (NSC) and then investigated the ability of these exosomes to induce differentiation into BMSCs under different culture conditions. The expression levels of key proteins and gene markers were detected in induced cells by fluorescence immunoassays, western blotting and polymerase chain reaction (PCR); then, we statistically compared the relative induction effects under different conditions. Finally, we analyzed the three types of exosomes by RNA-seq to predict target genes and related gene pathways. RESULTS: BMSCs were cultured by three media: conventional (no induction), pre-induction or pre-induction + original induction medium (ODM) with exosomes of the same cell origin under different culture conditions. When adding the three different types of exosomes separately, the overall induction of BMSCs to differentiate into SCs was significantly increased (P < 0.05). The induction ability was ranked as follows: pre-induction + ODM + exosome group > pre-induction + exosome group > non-induction + exosome group. Using exosomes from different cell sources under the same culture conditions, we observed the following trends under the three culture conditions: RSC96-exos group ≥ NSC-exos group > Fb-exos group. The overall ability to induce BMSCs into SCs was significantly greater in the RSC96-exos group and the NSC-exos group. Although there was no significant difference in induction efficiency when comparing these two groups, the overall induction ability of the RSC96-exos group was slightly higher than that of the NSC-exos group. By combining the differentiation induction results with the RNA-seq data, the three types of exosomes were divided into three comparative groups: RSC vs. NSC, RSC vs. Fb and NSC vs. Fb. We identified 203 differentially expressed mRNA target genes in these three groups. Two differentially expressed genes were upregulated simultaneously, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). We did not identify any co-upregulated target genes for the miRNAs, but did identify one target gene of the lncRNAs, namely ENSRNOG00000065005. Analysis identified 90 GO terms related to nerves and axons in the mRNAs; in addition, KEGG enrichment and GASA analysis identified 13 common differential expression pathways in the three groups. CONCLUSIONS: Our analysis found that pre-induction + ODM + RSC96/NSC-exos culture conditions were most conducive with regards to induction and differentiation. RSC96-exos and NSC-exos exhibited significantly greater differentiation efficiency of BMSCs into SCs. Although there was no statistical difference, the data indicated a trend for RSC96-exos to be advantageous We identified 203 differentially expressed mRNAs between the three groups and two differentially expressed target mRNAs were upregulated, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). 90 GO terms were related to nerves and axons. Finally, we identified 13 common differentially expressed pathways across our three types of exosomes. It is hoped that the efficiency of BMSCs induction differentiation into SCs can be improved, bringing hope to patients and more options for clinical treatment.

A cingulate-hippocampal circuit mediates early depressive-like behavior in the mouse model of Alzheimer disease.

Depressive symptoms usually precede the cognitive decline in Alzheimer disease (AD) and worsen the clinical outcome. However, the neural circuitry mediating early emotional dysfunction, especially depressive symptoms in AD, remains elusive. Anterior cingulate cortex (ACC) is closely related to depression and vulnerable in AD. By quantitative whole-brain mapping and electrophysiological recording, we found that the decreased axonal calcium activity in neurons of ACC and the glutamatergic projection from ACC to the ventral hippocampal CA1 (vCA1) is significantly impaired in 3-month-old 5×FAD mice, which exhibit depressive-like phenotype before cognition defects in early stage. The activation of ACC-vCA1 circuit by chemogenetic manipulation efficiently ameliorated the early depressive-like behaviors in 5×FAD mice. We further identified the upregulated neuregulin-1 (Nrg1) in ACC impaired the excitatory synaptic transmission from the ACC to vCA1 in AD. Our work reveals the role of ACC-vCA1 circuit in regulating AD associated depression symptom in a mouse model of AD.

Asymmetric Coordination Regulating D-orbital Spin-electron Filling in Single-atom Iron Catalyst for Efficient Oxygen Reduction.

The single-atom Fe-N-C catalyst has shown great promise for the oxygen reduction reaction (ORR), yet the intrinsic activity is not satisfactory. There is a pressing need to gain a deeper understanding of the charge configuration of the Fe-N-C catalyst and to develop rational modulation strategies. Herein, we have prepared a single-atom Fe catalyst with the co-coordination of N and O (denoted as Fe-N/O-C) and adjacent defect, proposing a strategy to optimize the d-orbital spin-electron filling of Fe sites by fine-tuning the first coordination shell. The Fe-N/O-C exhibits significantly better ORR activity compared to its Fe-N-C counterpart and commercial Pt/C, with a much more positive half-wave potential (0.927 V) and higher kinetic current density. Moreover, using the Fe-N/O-C catalyst, the Zn-air battery and proton exchange membrane fuel cell achieve peak power densities of up to 490 and 1179 mW cm-2, respectively. Theoretical studies and in situ electrochemical Raman spectroscopy reveal that Fe-N/O-C undergoes charge redistribution and negative shifting of the d-band center compared to Fe-N-C, thus optimizing the adsorption free energy of ORR intermediates. This work demonstrates the feasibility of introducing an asymmetric first coordination shell for single-atom catalysts and provides a new optimization direction for their practical application.

Obesity and Hypertension Mediate the Effect of Education on Deep Intracerebral Hemorrhage: A Mendelian Randomization Study.

BACKGROUND: Educational attainment (EA) as a stable indicator of socioeconomic status has been confirmed to affect intracerebral hemorrhage (ICH), but the mechanism relating EA and ICH is still unknown. AIM: To explore the causal relationship between EA and ICH through a bidirectional and two-step Mendelian randomization (MR) study. METHODS: Using summary-level Genome-wide Association Study (GWAS) data based from European ancestry, we performed bidirectional and two-step MR analyses to explore the causal relationship between educational attainment and ICH to understand the mediating influence of risk factors in this process. We also carried out subgroup analysis according to the different sites (deep and lobar) of ICH. A set of sensitivity analyses were performed to test valid MR assumptions. RESULTS: Bidirectional MR analysis consistently demonstrated a unidirectional causal effect, revealing that higher EA had a protective influence on ICH. Each additional 1-standard deviation (SD) increase in genetically predicted years of schooling was associated with a reduced risk of all ICH (inverse variance weighted (IVW) OR: 0.381 [95%CI: 0.264-0.549]), deep ICH (OR: 0.334 [95%CI: 0.216-0.517]), and lobar ICH (OR: 0.422 [95%CI: 0.261-0.682]). The mediating effect of EA on all ICH was mediated via systolic blood pressure (SBP) (6.93% [1.20-13.45%]) and body mass index (BMI) (17.87% [3.92-34.64%]), and the mediating effect of EA on deep ICH was also mediated via SBP (7.85% [1.55-15.07%]) and BMI (18.63% [4.02-36.26%]). CONCLUSION: This study provides robust genetic evidence for supporting the protective effect of EA on ICH risk, with further evidence that the effect of EA on deep ICH is partially mediated through hypertension and obesity. Further validation is needed to ascertain whether these findings are applicable to other racial or general population groups.

A General Molecular Structural Design for Highly Efficient Photopyroptosis that can be Activated within 10 s Irradiation.

Photopyroptosis is an emerging research branch of photodynamic therapy (PDT), whereas there remains a lack of molecular structural principles to fabricate photosensitizers for triggering a highly efficient pyroptosis. Herein, a general and rational structural design principle to implement this hypothesis, is proposed. The principle relies on the clamping of cationic moieties (e.g., pyridinium, imidazolium) onto one photosensitive core to facilitate a considerable mitochondrial targeting (both of the inner and the outer membranes) of the molecules, thus maximizing the photogenerated reactive oxygen species (ROS) at the specific site to trigger the gasdermin E-mediated pyroptosis. Through this design, the pyroptotic trigger can be achieved in a minimum of 10 s of irradiation with a substantially low light dosage (0.4 J cm⁻2), compared to relevant work reported (up to 60 J cm⁻2). Moreover, immunotherapy with high tumor inhibition efficiency is realized by applying the synthetic molecules alone. This structural paradigm is valuable for deepening the understanding of PDT (especially the mitochondrial-targeted PDT) from the perspective of pyroptosis, toward the future development of the state-of-the-art form of PDT.

A novel non-negative Bayesian stacking modeling method for Cancer survival prediction using high-dimensional omics data.

BACKGROUND: Survival prediction using high-dimensional molecular data is a hot topic in the field of genomics and precision medicine, especially for cancer studies. Considering that carcinogenesis has a pathway-based pathogenesis, developing models using such group structures is a closer mimic of disease progression and prognosis. Many approaches can be used to integrate group information; however, most of them are single-model methods, which may account for unstable prediction. METHODS: We introduced a novel survival stacking method that modeled using group structure information to improve the robustness of cancer survival prediction in the context of high-dimensional omics data. With a super learner, survival stacking combines the prediction from multiple sub-models that are independently trained using the features in pre-grouped biological pathways. In addition to a non-negative linear combination of sub-models, we extended the super learner to non-negative Bayesian hierarchical generalized linear model and artificial neural network. We compared the proposed modeling strategy with the widely used survival penalized method Lasso Cox and several group penalized methods, e.g., group Lasso Cox, via simulation study and real-world data application. RESULTS: The proposed survival stacking method showed superior and robust performance in terms of discrimination compared with single-model methods in case of high-noise simulated data and real-world data. The non-negative Bayesian stacking method can identify important biological signal pathways and genes that are associated with the prognosis of cancer. CONCLUSIONS: This study proposed a novel survival stacking strategy incorporating biological group information into the cancer prognosis models. Additionally, this study extended the super learner to non-negative Bayesian model and ANN, enriching the combination of sub-models. The proposed Bayesian stacking strategy exhibited favorable properties in the prediction and interpretation of complex survival data, which may aid in discovering cancer targets.

Effects of acupuncture for Bell's palsy patients in the acute phase and its impact on facial nerve edema: a study protocol for a randomized, controlled trial.

Background: Bell's palsy is an acute peripheral facial neuropathy, which is one of the most common causes of facial palsy of lower motor neurons. Facial nerve swelling is commonly observed in Bell's palsy. Acupuncture therapy has been widely used in the treatment of Bell's palsy. However, whether acupuncture can be effectively used in the acute stage is still controversial. There are no clinical trials conducted previously to evaluate the effect of acupuncture on facial nerve edema in Bell's palsy patients. The study aims to evaluate the potential efficacy of different acupuncture modalities on Bell's palsy patients in the acute phase, its effect on facial nerve edema, and to preliminarily explore its possible mechanism. Methods and analysis: In this randomized, controlled trial, 165 Bell's palsy patients with unilateral onset within 3 days will be recruited and randomly assigned to either the electroacupuncture group (n = 33), the acupuncture group (n = 33), the sham acupuncture group (n = 33), the blank control group (n = 33), or the acupuncture control group (n = 33) in a 1:1:1:1:1 ratio. The participants will receive 4 weeks of treatment and 8 weeks of follow-up. The five groups of participants will receive the following treatments: A: Electroacupuncture + Medication (prednisone acetate tablets, mecobalamin tablets, and vitamin B1 tablets); B: Acupuncture + Medication; C: Sham Acupuncture + Medication; D: Medication only; and E: Acupuncture only. The primary outcome will be the effectiveness rate of different acupuncture modalities in improving facial nerve function after the intervention period. The secondary outcomes will be the recovery speed, the diameter of the facial nerve, the echo intensity and thickness of facial muscles, blood flow parameters of the facial artery, the serum inflammatory level, safety evaluation, and adverse events. Preliminary exploration of its mechanism of action occurs through inflammation and immune response. The difference between groups will be assessed using repeated measure analysis of covariance (ANCOVA) and trend chi-square. Discussion: The trial will evaluate the efficacy and facial nerve edema of acupuncture for Bell's palsy patients in the acute phase and preliminarily explore its possible mechanism. The results thus may provide evidence for clinical application. Clinical trial registration: https://www.chictr.org.cn/bin/project/edit?pid=133211, identifier ChiCTR2100050815.

Screening and validation of atherosclerosis PAN-apoptotic immune-related genes based on single-cell sequencing.

Background: Carotid atherosclerosis (CAS) is a complication of atherosclerosis (AS). PAN-optosome is an inflammatory programmed cell death pathway event regulated by the PAN-optosome complex. CAS's PAN-optosome-related genes (PORGs) have yet to be studied. Hence, screening the PAN-optosome-related diagnostic genes for treating CAS was vital. Methods: We introduced transcriptome data to screen out differentially expressed genes (DEGs) in CAS. Subsequently, WGCNA analysis was utilized to mine module genes about PANoptosis score. We performed differential expression analysis (CAS samples vs. standard samples) to obtain CAS-related differentially expressed genes at the single-cell level. Venn diagram was executed to identify PAN-optosome-related differential genes (POR-DEGs) associated with CAS. Further, LASSO regression and RF algorithm were implemented to were executed to build a diagnostic model. We additionally performed immune infiltration and gene set enrichment analysis (GSEA) based on diagnostic genes. We verified the accuracy of the model genes by single-cell nuclear sequencing and RT-qPCR validation of clinical samples, as well as in vitro cellular experiments. Results: We identified 785 DEGs associated with CAS. Then, 4296 module genes about PANoptosis score were obtained. We obtained the 7365 and 1631 CAS-related DEGs at the single-cell level, respectively. 67 POR-DEGs were retained Venn diagram. Subsequently, 4 PAN-optosome-related diagnostic genes (CNTN4, FILIP1, PHGDH, and TFPI2) were identified via machine learning. Cellular function tests on four genes showed that these genes have essential roles in maintaining arterial cell viability and resisting cellular senescence. Conclusion: We obtained four PANoptosis-related diagnostic genes (CNTN4, FILIP1, PHGDH, and TFPI2) associated with CAS, laying a theoretical foundation for treating CAS.

A sensitive Ag+-mediated magnetic relaxation and colorimetry dual-mode sensing platform.

To address the relatively low sensitivity of current redox reagent-mediated magnetic relaxation sensing methods, we present a novel Ag+-mediated magnetic sensing platform that enhances the sensitivity by three orders of magnitude. The new sensing platform is based on Ag+-catalyzed oxidation of Mn2+ to KMnO4, accompanied by a distinct color change, which facilitates colorimetric detection. In the case of insufficient Ag+ ions, MnO2 is an additional oxidation product and the KMnO4/MnO2 ratio is dependent on the concentration of Ag+. When combined with a specific quantity of reducing agent, both KMnO4 and MnO2 are reduced to Mn2+ with a large relaxivity, and the concentration of Mn2+ in the resultant solution inversely correlates with the amount of KMnO4 since KMnO4 consumes more reductant during reduction. Consequently, the transverse relaxation rate of the solution exhibits a negative correlation with the Ag+ concentration. Thus, by coupling this Ag+-mediated Mn2+ to KMnO4 transformation with reactions that modulate Ag+ concentration, a dual-mode sensing platform for magnetic relaxation and colorimetry can be realized. Herein, we take H2O2 as an example to verify the detection performance of this sensing platform since H2O2 can oxidize Ag0 in Ag@Fe3O4 nanoparticles to Ag+. Experimental findings demonstrate detection limits of 10 nM and 20 nM for the magnetic relaxation and colorimetry modes, respectively, affirming the excellent sensitivity and the potential practical application of this strategy.

Edible Long-Afterglow Photoluminescent Materials for Bioimaging.

Confining luminophores into modified hydrophilic matrices or polymers is a straightforward and widely used approach for afterglow bioimaging. However, the afterglow quantum yield and lifetime of the related material remain unsatisfactory, severely limiting the using effect especially for deep-tissue time-resolved imaging. This fact largely stems from the dilemma between material biocompatibility and the quenching effect of water environment. We herein present an in situ metathesis promoted doping strategy, namely, mixing ∼10-3 weight ratio of organic-emitter multicarboxylates with inorganic salt reactants, followed by metathesis reactions to prepare a series of hydrophilic but water-insoluble organic-inorganic doping afterglow materials. This strategy led to the formation of edible long-afterglow photoluminescent materials with superior biocompatibility and excellent bioimaging effect. The phosphorescence quantum yield of the materials can reach dozens of percent (the highest case: 66.24%), together with the photoluminescent lifetime lasting for coupes of seconds. Specifically, a long-afterglow barium meal formed by coronene salt emitter and BaSO4 matrix was applied into animal experiments by gavage, and bright stomach afterglow imaging was observed by instruments or mobile phone after ceasing the photoexcitation with deep tissue penetration. This strategy allows a flexible dosage of the materials during bioimaging, facilitating the development of real-time probing and theranostic technology. This article is protected by copyright. All rights reserved.

Risk factors and outcomes for refeeding syndrome in acute ischaemic stroke patients.

AIM: Patients with acute ischaemic stroke are more likely to develop refeeding syndrome due to increased need for nutritional support when suffering alterations of consciousness and impairment of swallowing. This study aimed to evaluate the incidence, risk factors and outcomes of refeeding syndrome in stroke patients. METHODS: This was a retrospective observational study, using the prospective stroke database from hospital, included all consecutive acute ischaemic stroke patients who received enteral nutrition for more than 72 h from 1 January 2020 and 31 December 2022. Refeeding syndrome was defined as occurrence of new-onset hypophosphataemia within 72 h after enteral feeding. Multiple logistic regression analysis was conducted to evaluate risk factors and relationships between refeeding syndrome and stroke outcomes. RESULTS: 338 patients were included in the study. 50 patients (14.8%) developed refeeding syndrome. Higher scores on National Institutes of Health Stroke Scale and Nutritional Risk Screening 2002, albumin <30 g/L and BMI <18.5 kg/m2 were risk factors for refeeding syndrome. Moreover, refeeding syndrome was independently associated with a 3-month modified Rankin Scale score of >2 and 6-month mortality. CONCLUSIONS: Refeeding syndrome was common in stroke patients and higher baseline National Institutes of Health Stroke Scale, higher Nutritional Risk Screening 2002, albumin <30 g/L and BMI <18.5 kg/m2 were independent risk factors of refeeding syndrome. Occurrence of refeeding syndrome was significantly associated with higher 3-month modified Rankin Scale and 6-month mortality.

Prognostic value of the advanced lung cancer inflammation index in patients with gastric cancer after radical gastrectomy: a propensity-score matching cohort study and meta-analysis.

BACKGROUND: Insufficient evidence existed about the prognostic role of the advanced lung cancer inflammation index (ALI) for gastric cancer patients who underwent curative resection. The aim of this study was to identify the predictive ability of ALI for survival after curative gastrectomy. METHODS: We retrospectively analyzed 328 gastric cancer patients who received curative gastrectomy from the database of Chongqing University Cancer Hospital, and investigated the prognostic role of the preoperative ALI compared with clinicopathological variables and other serum biomarkers, such as preoperative neutrophil-to-lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and Lymphocyte-monocyte ratio (LMR). To minimize intergroup differences, propensity score matching (PSM) analysis was employed. Additionally, we performed a meta-analysis of four cohort studies published up to October 2023 following the PRISMA guidelines. RESULTS: In the overall cohort, patients in the low ALI group had a significantly worse overall survival compared to those in the high ALI group (P < 0.0001). Subgroup analysis identified that ALI maintained its prognostic significance across different subgroups. In addition, ROC analysis showed that ALI had a higher AUC value for 3-year overall survival compared to NLR, PLR, and LMR (0.576 vs. 0.573 vs. 0.557 vs. 0.557). Multivariate analysis indicated that ALI, other than other serum biomarkers, was an independent risk factor for decreased overall survival in GC patients following curative surgery (HR = 1.449; 95%CI: 1.028-2.045; P = 0.034). Consistently, PSM analysis supported all of these findings. The meta-analysis including 4 studies evaluating 2542 patients, confirmed the association between the low ALI and poor survival outcomes. CONCLUSION: The preoperative ALI was an independent prognostic factor for survival in gastric cancer patients who underwent curative gastrectomy.

Bispecific antibodies targeting CD20xCD3 in immunotherapy for adult B-cell lymphoma: insights from the 65th American Society of Hematology 2023 annual meeting.

INTRODUCTION: At the 65th American Society of Hematology (ASH) 2023 Annual Meeting, the latest advancements in CD20×CD3 BsAbs for B-cell lymphoma (BCL) were highlighted, particularly in relapsed/refractory (R/R) follicular lymphoma (FL) and R/R diffuse large B-cell lymphoma (DLBCL). AREAS COVERED: This summary highlights some of the major studies on CD20×CD3 BsAbs for BCL. EXPERT OPINION/COMMENTARY: CD20×CD3 is the most widely studied BsAb, with promising results in patients with R/R DLBCL and R/R FL ≥ two prior lines of systemic therapy. Trials with the first line of B-cell lymphoma also revealed promising results. Hopefully, BsAb monotherapy or BsAb-containing regimens may become the standard therapy in patients with FL and DLBCL.

Ligand-dependent folding and unfolding dynamics and free energy landscapes of acylphosphatase.

Acylphosphatase (AcP) is an enzyme which catalyses the hydrolysis of acylphosphate. The binding with the phosphate ion (Pi) assumes significance in preserving both the stability and enzymatic activity of AcP. While previous studies using single molecule force spectroscopy explored the mechanical properties of AcP, the influence of Pi on its folding and unfolding dynamic behaviors remains unexplored. In this work, using stable magnetic tweezers, we measured and compared the force-dependent folding and unfolding rates of AcP in the Tris buffer and phosphate buffer within a force range from 2 pN to 40 pN. We found that Pi exerts no discernible effect on the folding dynamics but consistently decreases the force-dependent unfolding rate of AcP by a constant ratio across the entire force spectrum. The free energy landscapes of AcP in the absence and presence of Pi are constructed. Our results reveal that Pi selectively binds to the native state of AcP, stabilizing it and suggesting the general properties of specific ligand-receptor interactions.

Anti-osteoporosis activity of casticin in ovariectomized rats.

Background: Postmenopausal osteoporosis (PMPO) is the most familiar type of osteoporosis, a silent bone disease. Casticin, a natural flavonoid constituent, improves osteoporosis in animal model. Nevertheless, the potential mechanism remains to be further explored. Methods: A model of PMPO was established in rats treated with ovariectomy (OVX) and RAW 264.7 cells induced with receptor activator of nuclear factor kappa-B ligand (RANKL). The effect and potential mechanism of casticin on PMPO were addressed by pathological staining, measurement of bone mineral density (BMD), three-point bending test, serum biochemical detection, filamentous-actin (F-actin) ring staining, TRAcP staining, reverse transcription quantitative polymerase chain reaction, western blot and examination of oxidative stress indicators. Results: The casticin treatment increased the femoral trabecular area, bone maturity, BMD, elastic modulus, maximum load, the level of calcium and estrogen with the reduced concentrations of alkaline phosphatase (ALP) and tumor necrosis factor (TNF)-α in OVX rats. An enhancement in the F-actin ring formation, TRAcP staining and the relative mRNA expression of NFATc1 and TRAP was observed in RANKL-induced RAW 264.7 cells, which was declined by the treatment of casticin. Moreover, the casticin treatment reversed the reduced the relative protein expression of Nrf2 and HO-1 and the concentrations of superoxide dismutase and glutathione peroxidase, and the increased content of malondialdehyde both in vivo and in vitro. Conclusion: Casticin improved bone density, bone biomechanics, the level of calcium and estrogen, the release of pro-inflammatory factor and oxidative stress to alleviate osteoporosis, which was associated with the upregulation of Nrf2/HO-1 pathway.

Crystallization-induced emission from F-doped carbon dots.

Herein, F-doped CDs with bright red SSF were synthesized by a solvothermal method using trifluoroethanol as the solvent and m-hydroxybenzaldehyde as the carbon source. Strong F-F interactions are vital for inducing crystallization, and solid luminescence is achieved by blocking the nonradiative energy dissipation pathways of crystalline organizations.

Cervicovaginal microbiota: a promising direction for prevention and treatment in cervical cancer.

Cervical cancer is a common malignancy in women, with high incidence rate and mortality. Persistent infection of high-risk human papillomavirus (HPV) is the most important risk factor for cervical cancer and precancerous lesions. Cervicovaginal microbiota (CVM) plays an essential role in the defense of HPV infections and prevention of subsequent lesions. Dominance of Lactobacillus is the key of CVM homeostasis, which can be regulated by host, exogenous and endogenous factors. Dysbiosis of CVM, including altered microbial, metabolic, and immune signatures, can contribute to persist HPV infection, leading to cervical cancer. However, there is no evidence of the causality between CVM and cervical cancer, and the underlying mechanism remains unexplored. Considering the close correlation between CVM dysbiosis and persistent HPV infection, this review will overview CVM, its role in cervical cancer development and related mechanisms, and the prospects for therapeutic applications.