GRM2 Regulates Functional Integration of Adult-Born DGCs by Paradoxically Modulating MEK/ERK1/2 Pathway.

Metabotropic glutamate receptor 2 (GRM2) is highly expressed in hippocampal dentate granule cells (DGCs), regulating synaptic transmission and hippocampal functions. Newborn DGCs are continuously generated throughout life and express GRM2 when they are mature. However, it remained unclear whether and how GRM2 regulates the development and integration of these newborn neurons. We discovered that the expression of GRM2 in adult-born DGCs increased with neuronal development in mice of both sexes. Lack of GRM2 caused developmental defects of DGCs and impaired hippocampus-dependent cognitive functions. Intriguingly, our data showed that knockdown of Grm2 resulted in decreased b/c-Raf kinases and paradoxically led to an excessive activation of MEK/ERK1/2 pathway. Inhibition of MEK ameliorated the developmental defects caused by Grm2 knockdown. Together, our results indicate that GRM2 is necessary for the development and functional integration of newborn DGCs in the adult hippocampus through regulating the phosphorylation and activation state of MEK/ERK1/2 pathway.SIGNIFICANCE STATEMENT Metabotropic glutamate receptor 2 (GRM2) is highly expressed in mature dentate granule cells (DGCs) in the hippocampus. It remains unclear whether GRM2 is required for the development and integration of adult-born DGCs. We provided in vivo and in vitro evidence to show that GRM2 regulates the development of adult-born DGCs and their integration into existing hippocampal circuits. Lack of GRM2 in a cohort of newborn DGCs impaired object-to-location memory in mice. Moreover, we revealed that GRM2 knockdown paradoxically upregulated MEK/ERK1/2 pathway by suppressing b/c-Raf in developing neurons, which is likely a common mechanism underlying the regulation of the development of neurons expressing GRM2. Thus, Raf/MEK/ERK1/2 pathway could be a potential target for brain diseases related to GRM2 abnormality.

Altitudinal variation of dragon fruit metabolite profiles as revealed by UPLC-MS/MS-based widely targeted metabolomics analysis.

BACKGROUND: Geographical factors affect the nutritional, therapeutic and commercial values of fruits. Dragon fruit (Hylocereus spp) is a popular fruit in Asia and a potential functional food with diverse pharmacological attributes. Although it is produced in various localities, the information related to the altitudinal variation of dragon fruit nutrients and active compounds is scarce. Hence, this study aimed to investigate the variations in metabolite profiles of H. polyrhizus (variety Jindu1) fruit pulps from three different altitudes of China, including Wangmo (WM, 650 m), Luodian (LD, 420 m), and Zhenning (ZN, 356 m). Jindu1 is the main cultivated pitaya variety in Guizhou province, China. RESULTS: The LC-MS (liquid chromatography-mass spectroscopy)-based widely targeted metabolic profiling identified 645 metabolites, of which flavonoids (22.64%), lipids (13.80%), phenolic acids (12.40%), amino acids and derivatives (10.39%), alkaloids (8.84%), and organic acids (8.37%) were dominant. Multivariate analyses unveiled that the metabolite profiles of the fruit differed regarding the altitude. Fruits from WM (highest altitude) were prime in quality, with higher levels of flavonoids, alkaloids, nucleotides and derivatives, amino acids and derivatives, and vitamins. Fruits from LD and ZN had the highest relative content of phenolic acids and terpenoids, respectively. We identified 69 significantly differentially accumulated metabolites across the pulps of the fruits from the three locations. KEGG analysis revealed that flavone and flavonol biosynthesis and isoflavonoid biosynthesis were the most differentially regulated. It was noteworthy that most active flavonoid compounds exhibited an increasing accumulation pattern along with the increase in altitude. Vitexin and isovitexin were the major differentially accumulated flavonoids. Furthermore, we identified two potential metabolic biomarkers (vitexin and kaempferol 3-O-[2-O-ß-D-galactose-6-O-a-L-rhamnose]-ß-D-glucoside) to discriminate between dragon fruits from different geographical origins. CONCLUSION: Our findings provide insights into metabolic changes in dragon fruits grown at different altitudes. Furthermore, they show that growing pitaya at high altitudes can produce fruit with higher levels of bioactive compounds, particularly flavonoids.

The Protective Role of Transcript-Induced in Spermiogenesis 40 in Cerebral Ischemia-Reperfusion Injury.

Prompt reperfusion after cerebral ischemia is important to maintain neuronal survival and reduce permanent disability and death. However, the resupply of blood can induce oxidative stress, inflammatory response and apoptosis, further leading to tissue damage. Here, we report the versatile biological roles of transcript-induced in spermiogenesis 40 (Tisp40) in ischemic stroke. We found that the expression of Tisp40 was upregulated in ischemia/reperfusion-induced brain tissues and oxygen glucose deprivation/returned -stimulated neurons. Tisp40 deficiency increased the infarct size and neurological deficit score, and promoted inflammation and apoptosis. Tisp40 overexpression played the opposite role. In vitro, the oxygen glucose deprivation/returned model was established in Tisp40 knockdown and overexpression primary cultured cortical neurons. Tisp40 knockdown can aggravate the process of inflammation and apoptosis, and Tisp40 overexpression ameliorated the aforementioned processes. Mechanistically, Tisp40 protected against ischemic stroke via activating the AKT signaling pathway. Tisp40 may be a new therapeutic target in brain ischemia/reperfusion injury.

Enhanced Efficiency and Stability of Inverted CsPbI2Br Perovskite Solar Cells via Fluorinated Organic Ammonium Salt Surface Passivation.

All-inorganic perovskite solar cells (PSCs) have recently received increasing attention due to their outstanding thermal stability. However, the performance of these devices, especially for the devices with a p-i-n structure, is still inferior to that of the typical organic-inorganic counterparts. In this study, we introduce phenylammonium iodides with different side groups on the surface of the CsPbI2Br perovskite film and investigate their passivation effects. Our studies indicate that the 4-trifluoromethyl phenylammonium iodide (CFPA) molecule with the -CF3 side group effectively decreases the trap density of the perovskite film by forming interactions with the undercoordinated Pb2+ ions and significantly inhibits the nonradiative recombination in the derived PSC, leading to an enhanced open-circuit voltage (Voc) from 0.96 to 1.10 V after passivation. Also, the CFPA post-treatment enables better energy-level alignment between the conduction band minimum of CsPbI2Br perovskite and [6,6]-phenyl C61 butyric acid methyl ester, thereby enhancing the charge extraction from the perovskite to the charge transport layer. These combined benefits result in a significant enhancement of the power conversion efficiency from 11.22 to 14.37% for inverted CsPbI2Br PSCs. The device without encapsulation exhibits a degradation of only ≈4% after 1992 h in a N2 glovebox.

Clinically Applicable Pan-Origin Cancer Detection for Lymph Nodes via Artificial Intelligence-Based Pathology.

INTRODUCTION: Lymph node metastasis is one of the most common ways of tumour metastasis. The presence or absence of lymph node involvement influences the cancer's stage, therapy, and prognosis. The integration of artificial intelligence systems in the histopathological diagnosis of lymph nodes after surgery is urgent. METHODS: Here, we propose a pan-origin lymph node cancer metastasis detection system. The system is trained by over 700 whole-slide images (WSIs) and is composed of two deep learning models to locate the lymph nodes and detect cancers. RESULTS: It achieved an area under the receiver operating characteristic curve (AUC) of 0.958, with a 95.2% sensitivity and 72.2% specificity, on 1,402 WSIs from 49 organs at the National Cancer Center, China. Moreover, we demonstrated that the system could perform robustly with 1,051 WSIs from 52 organs from another medical centre, with an AUC of 0.925. CONCLUSION: Our research represents a step forward in a pan-origin lymph node metastasis detection system, providing accurate pathological guidance by reducing the probability of missed diagnosis in routine clinical practice.

Fluorinated organic ammonium salt passivation for high-efficiency and stable inverted CsPbI2Br perovskite solar cells.

All-inorganic CsPbI2Br inverted perovskite solar cells (PSCs) have drawn increasing attention because of their outstanding thermal stability and compatible process with tandem cells. However, relatively low open circuit voltage (Voc) has lagged their progress far behind theoretical limits. Herein, we introduce phenylmethylammonium iodide and 4-trifluoromethyl phenylmethylammonium iodide (CFPMAI) on the surface of a CsPbI2Br perovskite film and investigate their passivation effects. It is found that CFPMAI with a -CF3 substituent significantly decreases the trap density of the perovskite film by forming interactions with the under-coordinated Pb2+ ions and effectively suppresses the non-radiative recombination in the resulting PSC. In addition, CFPMAI surface passivation facilitates the optimization of energy-level alignment at the CsPbI2Br perovskite/[6,6]-phenyl C61 butyric acid methyl ester interface, resulting in improved charge extraction from the perovskite to the charge transport layer. Consequently, the optimized inverted CsPbI2Br device exhibits a markedly improved champion efficiency of 14.43% with a Voc of 1.12 V, a Jsc of 16.31 mA/cm2, and a fill factor of 79.02%, compared to the 10.92% (Voc of 0.95 V) efficiency of the control device. This study confirms the importance of substituent groups on surface passivation molecules for effective passivation of defects and optimization of energy levels, particularly for Voc improvement.

Methyltransferase-like 3 modulates osteogenic differentiation of adipose-derived stem cells in osteoporotic rats.

BACKGROUND: Osteoporosis (OP) is a metabolic bone disease involving reduced bone mass. Adipose-derived stem cells (ASCs) play an important role in bone regeneration. Emerging evidence suggests that methyltransferase-like 3 (METTL3) plays a significant role in bone development and metabolism. Therefore, this study investigates changes to METTL3 in the osteogenic differentiation of adipose stem cells in osteoporotic rats (OP-ASCs) and explores ways to enhance their osteogenic ability. METHODS: An animal model of osteoporosis was established by removing both ovaries in rats. Real-time PCR and western blotting were performed to detect the expression of METTL3 and bone-related molecules, including runt-related transcription factor 2 (Runx2) and osteopontin (Opn). Furthermore, alkaline phosphatase staining was used to confirm the osteogenic potential of stem cells. Mettl3 small interfering RNA and Mettl3 overexpression lentivirus were used to assess the role of METTL3 in osteogenic differentiation of ASCs and OP-ASCs. RESULTS: The osteogenic differentiation capacity and Mettl3 expression significantly decreased in OP-ASCs. Moreover, Mettl3 silencing down-regulated the osteogenic ability of ASCs, and overexpression of Mettl3 recovered the impaired osteogenic capacity in OP-ASCs in vitro. CONCLUSION: The Mettl3 expression levels and osteogenic potential of OP-ASCs decreased. However, overexpression of METTL3 rescued the osteogenic ability of OP-ASCs, providing a new target for treatment of osteoporotic bone defects.

Aberration free synthetic aperture second harmonic generation holography.

Second harmonic generation (SHG) microscopy is a valuable tool for optical microscopy. SHG microscopy is normally performed as a point scanning imaging method, which lacks phase information and is limited in spatial resolution by the spatial frequency support of the illumination optics. In addition, aberrations in the illumination are difficult to remove. We propose and demonstrate SHG holographic synthetic aperture holographic imaging in both the forward (transmission) and backward (epi) imaging geometries. By taking a set of holograms with varying incident angle plane wave illumination, the spatial frequency support is increased and the input and output pupil phase aberrations are estimated and corrected - producing diffraction limited SHG imaging that combines the spatial frequency support of the input and output optics. The phase correction algorithm is computationally efficient and robust and can be applied to any set of measured field imaging data.

A short period of early life oxytocin treatment rescues social behavior dysfunction via suppression of hippocampal hyperactivity in male mice.

Early sensory experiences interact with genes to shape precise neural circuits during development. This process is vital for proper brain function in adulthood. Neurological dysfunctions caused by environmental alterations and/or genetic mutation may share the same molecular or cellular mechanisms. Here, we show that early life bilateral whisker trimming (BWT) subsequently affects social discrimination in adult male mice. Enhanced activation of the hippocampal dorsal CA3 (dCA3) in BWT mice was observed during social preference tests. Optogenetic activation of dCA3 in naive mice impaired social discrimination, whereas chemogenetic silencing of dCA3 rescued social discrimination deficit in BWT mice. Hippocampal oxytocin (OXT) is reduced after whisker trimming. Neonatal intraventricular compensation of OXT relieved dCA3 over-activation and prevented social dysfunction. Neonatal knockdown of OXT receptor in dCA3 mimics the effects of BWT, and cannot be rescued by OXT treatment. Social behavior deficits in a fragile X syndrome mouse model (Fmr1 KO mice) could also be recovered by early life OXT treatment, through negating dCA3 over-activation. Here, a possible avenue to prevent social dysfunction is uncovered.

Extracellular vesicle-mediated delivery of miR-127-3p inhibits the proliferation and invasion of choriocarcinoma cells by targeting ITGA6.

BACKGROUND: Choriocarcinoma (CC) is a highly aggressive malignant tumor that mostly occurs in women of childbearing age. Chemotherapy is the main treatment for CC, but it has side effects and causes drug resistance, which can lead to treatment failure. Extracellular vesicles (EVs) that deliver microRNAs (miRNAs) have emerged as a novel and promising therapeutic tool for inhibiting tumor progression and metastasis. This research aimed to study the effects of miR-127-3p-enriched EVs (EV-miR-127-3p) on CC and underlying mechanisms. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were performed to determine the miR-127-3p and integrin subunit alpha-6 (ITGA6) expression levels. The interaction between miR-127-3p and ITGA6 was confirmed by a dual-luciferase reporter assay. Human umbilical cord mesenchymal stem cells (hUCMSCs) were identified using flow cytometry and multilineage differentiation. Uptake of labeled EVs was demonstrated using immunofluorescence staining and flow cytometry assays. EV-miR-127-3p were isolated from the culture medium of hUCMSCs and co-cultured with JEG-3 or JAR cells to evaluate their effects on cell proliferation, invasion, migration, and apoptosis, using the cell counting kit-8, Transwell, and flow cytometry assays. Epithelial-mesenchymal transition (EMT) and the transforming growth factor (TGF)-ß1/Smad pathway were investigated using qRT-PCR and western blotting. RESULTS: The expression of miR-127-3p was downregulated, while that of ITGA6 was upregulated in CC cell lines. ITGA6 was identified as a target gene of miR-127-3p. EV-miR-127-3p could inhibit the proliferation, invasion, migration, and promote the apoptosis of CC cells. We observed that EV-miR-127-3p suppressed EMT of CC cells by targeting ITGA6. In addition, the knockdown of ITGA6 inhibited the TGF-ß1/Smad pathway and reversed the EMT-promoting effect. CONCLUSION: These results indicate that EV-miR-127-3p from hUCMSCs exhibits anti-tumor effects by targeting ITGA6, which may be used as a novel therapeutic strategy for CC treatment.

Homeostatic Regulation of Astrocytes by Visual Experience in the Developing Primary Visual Cortex.

During postnatal development, sensory experience shapes the organization and function of cortical circuits. Previous studies focusing on experience-dependent plasticity of neurons have revealed a variety of mechanisms underlying cortical circuit rewiring. Emerging evidence shows that astrocytes play important roles in shaping cortical circuits through extensive interactions with different types of neurons and other glia cells. However, it remains unclear how astrocytes respond to sensory experience during postnatal development. In the present study, we profiled the maturation of astrocytes in the primary visual cortex (V1) at different postnatal stages. We then investigated the anatomical and physiological changes of astrocytes in V1 induced by multiple types of visual experience within 4 postnatal weeks. Compared with monocular deprivation during the critical period, binocular deprivation showed stronger impact on reactive astrocytes in V1. Moreover, long-term binocular deprivation significantly reduced the density of reactive astrocytes in layer 2/3 of V1 while strengthening gap junction couplings between astrocytes at the same time. Therefore, our data demonstrated that cortical astrocytes could undergo homeostatic plasticity in response to long-term changes of sensory inputs. The plasticity of astrocytes may interact with the plasticity of neurons to cooperatively shape cortical circuit refinement during postnatal development.

Surface Engineering of Laser-Induced Graphene Enables Long-Term Monitoring of On-Body Uric Acid and pH Simultaneously.

Laser-induced graphene (LIG) suffers from serious decay in long-term biosensing, which greatly restricts its practical applications. Herein, we report a new strategy to engineer the LIG surface with Au clusters and chitosan sequentially to form a C-Au-LIG electrode with a superhydrophilic and highly conductive 3D graphene surface, which demonstrates superior performance and negligible decay in both long-term storage and practical usage in vitro and in vivo environments. Moreover, the C-Au-LIG electrode can be used for detecting uric acid (UA) and pH simultaneously from a single differential pulse voltammetry curve with low-detection limitation, high accuracy, and negligible interference with other sweat biomarkers. The integrated C-Au-LIG wearable biosensor was employed to continuously monitor the UA content in human sweat, which can well reflect the daily intake of purines for at least 10 days. Therefore, the C-Au-LIG electrode demonstrates significant application potential and provides inspiration for surface engineering of other biosensor materials and electrodes.

Manipulating Dual Bound States in the Continuum for Efficient Spatial Light Modulator.

Spatial light modulators (SLMs) that could control diverse optical properties are highly demanded by many optoelectronic systems. Recently, the integration of nonlinear χ(2) materials and metasurfaces has been recognized as a promising strategy for next-generation SLMs. However, their modulation efficiency still encounters challenges due to low quality factor and weak light-matter interaction. Here, we demonstrate an efficient SLM by manipulating the dual bound state in continuum (BIC) with the assistance of a binary-pore anodic alumina oxide template technique. The coexistence of symmetry-protected BIC and Fabry-Pérot BIC is obtained by a desirable sandwich configuration with a BIC metasurface and EO polymer, which efficiently restrain radiative loss and generate a strong quasi-BIC resonance. The assembled SLM with large absorption and Q-factor delivers a modulation depth of 77% and an f3 dB of nearly 100 MHz. This dual BIC metasurface provides potential for applications including switches, LIDAR, augmented and virtual reality, and so on.

Advances in the Study of Probiotics for Immunomodulation and Intervention in Food Allergy.

Food allergies are a serious food safety and public health issue. Soybean, dairy, aquatic, poultry, and nut products are common allergens inducing allergic reactions and adverse symptoms such as atopic dermatitis, allergic eczema, allergic asthma, and allergic rhinitis. Probiotics are assumed as an essential ingredient in maintaining intestinal microorganisms' composition. They have unique physiological roles and therapeutic effects in maintaining the mucosal barrier, immune function, and gastrointestinal tract, inhibiting the invasion of pathogenic bacteria, and preventing diarrhea and food allergies. Multiple pieces of evidence reveal a significant disruptive effect of probiotics on food allergy pathology and progression mechanisms. Thus, this review describes the allergenic proteins as an entry point and briefly describes the application of probiotics in allergenic foods. Then, the role of probiotics in preventing and curing allergic diseases by regulating human immunity through intestinal flora and intestinal barrier, modulating host immune active cells, and improving host amino acid metabolism are described in detail. The anti-allergic role of probiotics in the function and metabolism of the gastrointestinal tract has been comprehensively explored to furnish insights for relieving food allergy symptoms and preventing food allergy.

Time-Restricted Salutary Effects of Blood Flow Restoration on Venous Thrombosis and Vein Wall Injury in Mouse and Human Subjects.

BACKGROUND: Up to 50% of patients with proximal deep vein thrombosis (DVT) will develop the postthrombotic syndrome characterized by limb swelling and discomfort, hyperpigmentation, skin ulcers, and impaired quality of life. Although catheter-based interventions enabling the restoration of blood flow (RBF) have demonstrated little benefit on postthrombotic syndrome, the impact on the acuity of the thrombus and mechanisms underlying this finding remain obscure. In experimental and clinical studies, we examined whether RBF has a restricted time window for improving DVT resolution. METHODS: First, experimental stasis DVT was generated in C57/BL6 mice (n=291) by inferior vena cava ligation. To promote RBF, mice underwent mechanical deligation with or without intravenous recombinant tissue plasminogen activator administered 2 days after deligation. RBF was assessed over time by ultrasonography and intravital microscopy. Resected thrombosed inferior vena cava specimens underwent thrombus and vein wall histological and gene expression assays. Next, in a clinical study, we conducted a post hoc analysis of the ATTRACT (Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis) pharmacomechanical catheter-directed thrombolysis (PCDT) trial (NCT00790335) to assess the effects of PCDT on Venous Insufficiency Epidemiological and Economic Study quality-of-life and Villalta scores for specific symptom-onset-to-randomization timeframes. RESULTS: Mice that developed RBF by day 4, but not later, exhibited reduced day 8 thrombus burden parameters and reduced day 8 vein wall fibrosis and inflammation, compared with controls. In mice without RBF, recombinant tissue plasminogen activator administered at day 4, but not later, reduced day 8 thrombus burden and vein wall fibrosis. It is notable that, in mice already exhibiting RBF by day 4, recombinant tissue plasminogen activator administration did not further reduce thrombus burden or vein wall fibrosis. In the ATTRACT trial, patients receiving PCDT in an intermediate symptom-onset-to-randomization timeframe of 4 to 8 days demonstrated maximal benefits in Venous Insufficiency Epidemiological and Economic Study quality-of-life and Villalta scores (between-group difference=8.41 and 1.68, respectively, P<0.001 versus patients not receiving PCDT). PCDT did not improve postthrombotic syndrome scores for patients having a symptom-onset-to-randomization time of <4 days or >8 days. CONCLUSIONS: Taken together, these data illustrate that, within a restricted therapeutic window, RBF improves DVT resolution, and PCDT may improve clinical outcomes. Further studies are warranted to examine the value of time-restricted RBF strategies to reduce postthrombotic syndrome in patients with DVT.

Assessment of deep learning assistance for the pathological diagnosis of gastric cancer.

Previous studies on deep learning (DL) applications in pathology have focused on pathologist-versus-algorithm comparisons. However, DL will not replace the breadth and contextual knowledge of pathologists; rather, only through their combination may the benefits of DL be achieved. A fully crossed multireader multicase study was conducted to evaluate DL assistance with pathologists' diagnosis of gastric cancer. A total of 110 whole-slide images (WSI) (50 malignant and 60 benign) were interpreted by 16 board-certified pathologists with or without DL assistance, with a washout period between sessions. DL-assisted pathologists achieved a higher area under receiver operating characteristic curve (ROC-AUC) (0.911 vs. 0.863, P = 0.003) than unassisted in interpreting the 110 WSIs. Pathologists with DL assistance demonstrated higher sensitivity in detection of gastric cancer than without (90.63% vs. 82.75%, P = 0.010). No significant difference was observed in specificity with or without deep learning assistance (78.23% vs. 79.90%, P = 0.468). The average review time per WSI was shortened with DL assistance than without (22.68 vs. 26.37 second, P = 0.033). Our results demonstrated that DL assistance indeed improved pathologists' accuracy and efficiency in gastric cancer diagnosis and further boosted the acceptance of this new technique.

Electrical-Conductive/Insulating Bi-Functional Layers for Stable Zn Metal Anode.

Zinc-ion batteries are regarded as an extremely promising candidate for large-scale energy storage equipment due to the inexpensive ingredients and high safety. However, dendrite growth and side reactions occur in the Zn anode, which lead to exceedingly low coulombic efficiency (CE) and poor cycling stability. In this work, we propose a strategy of a conductive/insulating bi-functional coating layer (CIBL) for stable Zn metal anodes. Porous Ag nanowires (NWs) coating as a conductive layer effectively reduces the nuclear barrier and contains Zn2+ deposition in a certain space. Polyimide (PI) coatings as insulating layer implement a shunting effect on Zn2+ , which could reduce the differential concentration on the Zn surface and induce uniform deposition of Zn2+ . Therefore, the CIBL-Zn//CIBL-Zn battery achieves stable plating/stripping of over 1300 h at 1 mA cm-2 . The CE of CIBL-Zn//CIBL-Zn battery maintains at 99.2 % even after 1000 cycles. Moreover, the CIBL-Zn//V2 O5 battery exhibits a capacity of nearly 289.2 mA h g-1 at 5 A g-1 after 3000 cycles and no sign of capacity degradation is found, which further demonstrate the feasibility of this strategy in practical application.

Effect of thrombomodulin gene polymorphisms on venous thromboembolism: An analysis of evidence involving 6,629 patients.

BACKGROUD: The association between thrombomodulin gene (THBD) c.1418 C>T polymorphisms and the risk of venous thromboembolism (VTE) is controversial. The purpose of this meta-analysis was to evaluate THBD c.1418 C>T polymorphisms and the risk of VTE. METHODS: Computer searches were performed on the CNKI, Wanfang database, VIP database, PubMed, Embase, Web of Science, and Cochrane Library databases. The retrieval time limit was from the establishment of the database to June 2022. Case-control studies and cohort studies of THBD c.1418 C>T polymorphisms associated with VTE were included. The literature was screened according to inclusion and exclusion criteria, data extraction and literature quality evaluation. Meta-analysis was performed using STATA 14.0 software. RESULTS: A total of 12 literature were included, including 2980 cases in the case group and 3649 cases in the control group. The meta-analysis results showed no significant association of the THBD c.1418 C> T polymorphisms with the occurrence of VTE (T vs C: OR = 1.17, 95%CI = 0.93-1.48; TT vs CT+CC: OR = 1.00, 95%CI = 0.75-1.33; TT+CT vs CC: OR = 1.22, 95%CI = 0.94-1.59). Subgroup analyses revealed an increased risk of VTE in Asian populations due to THBD c.1418 C>T polymorphisms (T vs C: OR = 1.48, 95%CI = 1.06-2.07; TT vs CT+CC: OR = 1.80, 95%CI = 1.13-2.85; TT+CT vs CC: OR = 1.58, 95%CI = 1.07-2.32). THBD c.1418 C>T polymorphisms increased the risk of DVT (T vs C: OR = 1.51, 95%CI = 1.24-1.85; TT vs CT+CC: OR = 1.85, 95%CI = 1.10-3.12; TT+CT vs CC: OR = 1.64, 95%CI = 1.28-2.11). THBD c.1418 C>T polymorphisms reduced the risk of VTE in non-Asian populations (TT vs CT+CC: OR = 0.66, 95%CI = 0.45-0.98). CONCLUSION: THBD c.1418 C>T polymorphisms is associated with VTE in Asian population, which may be a factor in the occurrence of VTE in Asian population. THBD c.1418 C>T polymorphisms increases the risk of DVT. Given the limitations of this meta-analysis, the conclusions require being further supported by large-scale and high-quality studies.

Effects of carotid baroreceptor stimulation on aortic remodeling in obese rats.

BACKGROUND AND AIM: Our previous study found carotid baroreceptor stimulation (CBS) reduces body weight and white adipose tissue (WAT) weight, restores abnormal secretion of adipocytokines and inflammation factors, decreases systolic blood pressure (SBP) by inhibiting activation of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in obese rats. In this study, we explore effects of CBS on aortic remodeling in obese rats. METHODS AND RESULTS: Rats were fed high-fat diet (HFD) for 16 weeks to induce obesity and underwent either CBS device implantation and stimulation or sham operation at 8 weeks. BP and body weight were measured weekly. RAS activity of WAT, histological, biochemical and functional profiles of aortas were detected after 16 weeks. CBS effectively decreased BP in obese rats, downregulated mRNA expression of angiotensinogen (AGT) and renin in WAT, concentrations of AGT, renin, angiotensin II (Ang II), protein levels of Ang II receptor 1 (AT1R) and Ang II receptor 2 (AT2R) in WAT were declined. CBS inhibited reactive oxygen species (ROS) generation, inflammatory response and endoplasmic reticulum (ER) stress in aortas of obese rats, restrained vascular wall thickening and vascular smooth muscle cells (VSMCs) phenotypic switching, increased nitric oxide (NO) synthesis, promoted endothelium-dependent vasodilatation by decreasing protein expression of AT1R and leptin receptor (LepR), increasing protein expression of adiponectin receptor 1 (AdipoR1) in aortic VSMCs. CONCLUSION: CBS reduced BP and reversed aortic remodeling in obese rats, the underlying mechanism might be related to the suppressed SNS activity, restored adipocytokine secretion and restrained RAS activity of WAT.

One-photon red light-triggered disassembly of small-molecule nanoparticles for drug delivery.

BACKGROUND: Photoresponsive drug delivery can achieve spatiotemporal control of drug accumulation at desired sites. Long-wavelength light is preferable owing to its deep tissue penetration and low toxicity. One-photon upconversion-like photolysis via triplet-triplet energy transfer (TTET) between photosensitizer and photoresponsive group enables the use of long-wavelength light to activate short-wavelength light-responsive groups. However, such process requires oxygen-free environment to achieve efficient photolysis due to the oxygen quenching of triplet excited states. RESULTS: Herein, we report a strategy that uses red light to trigger disassembly of small-molecule nanoparticles by one-photon upconversion-like photolysis for cancer therapy. A photocleavable trigonal molecule, BTAEA, self-assembled into nanoparticles and enclosed photosensitizer, PtTPBP. Such nanoparticles protected TTET-based photolysis from oxygen quenching in normoxia aqueous solutions, resulting in efficient red light-triggered BTAEA cleavage, dissociation of nanoparticles and subsequent cargo release. With paclitaxel as the model drug, the red light-triggered drug release system demonstrated promising anti-tumor efficacy both in vitro and in vivo. CONCLUSIONS: This study provides a practical reference for constructing photoresponsive nanocarriers based on the one-photon upconversion-like photolysis.