Berberine Inhibits Ferroptosis and Stabilizes Atherosclerotic Plaque through NRF2/SLC7A11/GPX4 Pathway.

OBJECTIVE: To investigate potential mechanisms of anti-atherosclerosis by berberine (BBR) using ApoE-/- mice. METHODS: Eight 8-week-old C57BL/6J mice were used as a blank control group (normal), and 56 8-week-old AopE-/- mice were fed a high-fat diet for 12 weeks, according to a completely random method, and were divided into the model group, BBR low-dose group (50 mg/kg, BBRL), BBR medium-dose group (100 mg/kg, BBRM), BBR high-dose group (150 mg/kg, BBRH), BBR+nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor group (100 mg/kg BBR+30 mg/kg ML385, BBRM+ML385), NRF2 inhibitor group (30 mg/kg, ML385), and positive control group (2.5 mg/kg, atorvastatin), 8 in each group. After 4 weeks of intragastric administration, samples were collected and serum, aorta, heart and liver tissues were isolated. Biochemical kits were used to detect serum lipid content and the expression levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in all experimental groups. The pathological changes of atherosclerosis (AS) were observed by aorta gross Oil Red O, aortic sinus hematoxylin-eosin (HE) and Masson staining. Liver lipopathy was observed in mice by HE staining. The morphology of mitochondria in aorta cells was observed under transmission electron microscope. Flow cytometry was used to detect reactive oxygen species (ROS) expression in aorta of mice in each group. The content of ferrous ion Fe2+ in serum of mice was detected by biochemical kit. The mRNA and protein relative expression levels of NRF2, glutathione peroxidase 4 (GPX4) and recombinant solute carrier family 7 member 11 (SLC7A11) were detected by quantitative real time polymerase chain reaction (RT-qPCR) and Western blot, respectively. RESULTS: BBRM and BBRH groups delayed the progression of AS and reduced the plaque area (P<0.01). The characteristic morphological changes of ferroptosis were rarely observed in BBR-treated AS mice, and the content of Fe2+ in BBR group was significantly lower than that in the model group (P<0.01). BBR decreased ROS and MDA levels in mouse aorta, increased SOD activity (P<0.01), significantly up-regulated NRF2/SLC7A11/GPX4 protein and mRNA expression levels (P<0.01), and inhibited lipid peroxidation. Compared with the model group, the body weight, blood lipid level and aortic plaque area of ML385 group increased (P<0.01); the morphology of mitochondria showed significant ferroptosis characteristics; the serum Fe2+, MDA and ROS levels increased (P<0.05 or P<0.01), and the activity of SOD decreased (P<0.01). Compared with BBRM group, the iron inhibition effect of BBRM+ML385 group was significantly weakened, and the plaque area significantly increased (P<0.01). CONCLUSION: Through NRF2/SLC7A11/GPX4 pathway, BBR can resist oxidative stress, inhibit ferroptosis, reduce plaque area, stabilize plaque, and exert anti-AS effects.

[Application and prospects of hyperspectral remote sensing in monitoring plant diversity in grassland]. / é«˜å ‰è°±é¥æ„Ÿåœ¨è‰åŽŸæ¤ç‰©å¤šæ ·æ€§ç›‘æµ‹ä¸­çš„åº”ç”¨ä¸Žå±•æœ›.

The biodiversity of grasslands is important for ecosystem function and health. The protection and mana-gement of grassland biodiversity requires the collection of the information on plant diversity. Hyperspectral remote sensing, with its unique advantages of extensive coverage and high spectral resolution, offers a new solution for long-term monitoring of plant diversity. We first reviewed the development history of hyperspectral remote sensing technology, emphasized its advantages in monitoring grassland plant diversity, and further analyzed its specific applications in this field. Finally, we discussed the challenges faced by hyperspectral remote sensing technology in its applications, such as the complexity of data processing, accuracy of algorithms, and integration with ground-based remote sensing data, and proposes prospects for future research directions. With the advancement of remote sensing technology and the integrated application of multi-source data, hyperspectral remote sensing would play an increasingly important role in grassland ecological monitoring and biodiversity conservation, which could provide scientific basis and technical support for global ecological protection and sustainable development.

Carbon-based Flame Retardants for Polymers: A Bottom-up Review.

This state-of-the-art review is geared toward elucidating the molecular understanding of the carbon-based flame-retardant mechanisms for polymers via holistic characterization combining detailed analytical assessments and computational material science. The use of carbon-based flame retardants, which include graphite, graphene, carbon nanotubes (CNTs), carbon dots (CDs), and fullerenes, in their pure and functionalized forms are initially reviewed to evaluate their flame retardancy performance and to determine their elevation of the flammability resistance on various types of polymers. The early transition metal carbides such as MXenes, regarded as next-generation carbon-based flame retardants, are discussed with respect to their superior flame retardancy and multifunctional applications. At the core of this review is the utilization of cutting-edge molecular dynamics (MD) simulations which sets a precedence of an alternative bottom-up approach to fill the knowledge gap through insights into the thermal resisting process of the carbon-based flame retardants, such as the formation of carbonaceous char and intermediate chemical reactions offered by the unique carbon bonding arrangements and microscopic in-situ architectures. Combining MD simulations with detailed experimental assessments and characterization, a more targeted development as well as a systematic material synthesis framework can be realized for the future development of advanced flame-retardant polymers.

Fast, Accurate, and Versatile Data Analysis Platform for the Quantification of Molecular Spatiotemporal Signals.

Optical recording of intricate molecular dynamics is becoming an indispensable technique for biological studies, accelerated by the development of new or improved biosensors and microscopy technology. This creates major computational challenges to extract and quantify biologically meaningful spatiotemporal patterns embedded within complex and rich data sources, many of which cannot be captured with existing methods. Here, we introduce Activity Quantification and Analysis (AQuA2), a fast, accurate, and versatile data analysis platform built upon advanced machine learning techniques. It decomposes complex live imaging-based datasets into elementary signaling events, allowing accurate and unbiased quantification of molecular activities and identification of consensus functional units. We demonstrate applications across a wide range of biosensors, cell types, organs, animal models, and imaging modalities. As exemplar findings, we show how AQuA2 identified drug-dependent interactions between neurons and astroglia, and distinct sensorimotor signal propagation patterns in the mouse spinal cord.

High-integrity Pueraria montana var. lobata genome and population analysis revealed the genetic diversity of Pueraria genus.

Pueraria montana var. lobata (P. lobata) is a traditional medicinal plant belonging to the Pueraria genus of Fabaceae family. Pueraria montana var. thomsonii (P. thomsonii) and Pueraria montana var. montana (P. montana) are its related species. However, evolutionary history of the Pueraria genus is still largely unknown. Here, a high-integrity, chromosome-level genome of P. lobata and an improved genome of P. thomsonii were reported. It found evidence for an ancient whole-genome triplication and a recent whole-genome duplication shared with Fabaceae in three Pueraria species. Population genomics of 121 Pueraria accessions demonstrated that P. lobata populations had substantially higher genetic diversity, and P. thomsonii was probably derived from P. lobata by domestication as a subspecies. Selection sweep analysis identified candidate genes in P. thomsonii populations associated with the synthesis of auxin and gibberellin, which potentially play a role in the expansion and starch accumulation of tubers in P. thomsonii. Overall, the findings provide new insights into the evolutionary and domestication history of the Pueraria genome and offer a valuable genomic resource for the genetic improvement of these species.

Evaluation of a Standard Dietary Regimen Combined with Heat-Inactivated Lactobacillus gasseri HM1, Lactoferrin-Producing HM1, and Their Sonication-Inactivated Variants in the Management of Metabolic Disorders in an Obesity Mouse Model.

This study investigated the impact of incorporating various inactivated probiotic formulations, with or without recombinant lactoferrin (LF) expression, into a standard chow diet on metabolic-related disorders in obese mice. After inducing obesity through a 13-week high-fat diet followed by a standard chow diet, mice received daily oral administrations of different probiotics for 6 weeks using the oral gavage approach. These probiotic formulations consisted of a placebo (MRS), heat-inactivated Lactobacillus gasseri HM1 (HK-HM1), heat-killed LF-expression HM1 (HK-HM1/LF), sonication-killed HM1 (SK-HM1), and sonication-killed LF-expression HM1 (SK-HM1/LF). The study successfully induced obesity, resulting in worsened glucose tolerance and insulin sensitivity. Interestingly, the regular diet alone improved glucose tolerance, and the addition of inactivated probiotics further enhanced this effect, with SK-HM1/LF demonstrating the most noticeable improvement. However, while regular dietary intervention alone improved insulin sensitivity, probiotic supplementation did not provide additional benefits in this aspect. Inflammation in perirenal and epididymal fat tissues was partially alleviated by the regular diet and further improved by probiotics, particularly by SK-HM1, which showed the most significant reduction. Additionally, HK-HM1 and HK-HM1/LF supplements could contribute to the improvement of serum total triglycerides or total cholesterol, respectively. Overall, incorporating inactivated probiotics into a regular diet may enhance metabolic indices, and recombinant LF may offer potential benefits for improving glucose tolerance.

Immune to temperature interference sensor of carbon dioxide gas concentration based on a single modified fiber Bragg grating.

In this study, a novel method that can detect carbon dioxide (CO2) concentration and realize temperature immunity based on only one fiber Bragg grating (FBG) is proposed. The outstanding contribution lies in solving the temperature crosstalk issue of FBG and ensuring the accuracy of detection results under the condition of anti-temperature interference. To achieve immunity to temperature interference without changing the initial structure of FBG, the optical fiber cladding of FBG and adjacent optical fiber cladding at both ends of FBG are modified by a polymer coating. Moreover, a universal immune temperature demodulation algorithm is derived. The experimental results demonstrate that the temperature response sensitivity of the improved FBG is controlled within the range of 0.00407 nm/°C. Compared with the initial FBG (the temperature sensitivity of the initial FBG is 0.04 nm/°C), it decreases by nearly 10 times. Besides, the gas response sensitivity of FBG reaches 1.6 pm/ppm and has overwhelmingly ideal linearity. The detection error results manifest that the gas concentration error in 20 groups of data does not exceed 3.16 ppm. The final reproducibility research shows that the difference in detection sensitivity between the two sensors is 0.08 pm/ppm, and the relative error of linearity is 1.07%. In a word, the proposed method can accurately detect the concentration of CO2 gas and is efficiently immune to temperature interference. The sensor we proposed has the advantages of a simple production process, low cost, and satisfactory reproducibility. It also has the prospect of mass production.

Observation of Photoassociation Resonances in Ultracold Atom-Molecule Collisions.

We report on the observation of photoassociation resonances in ultracold collisions between ^{23}Na^{40}K molecules and ^{40}K atoms. We perform photoassociation in a long-wavelength optical dipole trap to form deeply bound triatomic molecules in electronically excited states. The atom-molecule Feshbach resonance is used to enhance the free-bound Franck-Condon overlap. The photoassociation into well-defined quantum states of excited triatomic molecules is identified by observing resonantly enhanced loss features. These loss features depend on the polarization of the photoassociation lasers, allowing us to assign rotational quantum numbers. The observation of ultracold atom-molecule photoassociation resonances paves the way toward preparing ground-state triatomic molecules, provides a new high-resolution spectroscopy technique for polyatomic molecules, and is also important to atom-molecule Feshbach resonances.

LncRNA RPARP-AS1 promotes the progression of osteosarcoma cells through regulating lipid metabolism.

Osteosarcoma (OS) is a highly malignant tumor, and its dysregulated lipid metabolism is associated with tumorigenesis and unfavorable prognosis. Interestingly, long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of lipid metabolism, exerting notable impacts on tumor proliferation. Nevertheless, the involvement of RPARP-AS1, a novel lipid metabolism-associated lncRNA, remains unexplored in the context of OS. This study aims to identify functionally relevant lncRNAs impacting OS proliferation and lipid metabolism and seeks to shed light on the upstream regulatory mechanisms governing lipogenic enzyme activity. Based on comprehensive bioinformatic analysis and the establishment of a risk model, we identified seven lncRNAs significantly associated with clinical characteristics and lipid metabolism-related genes in patients with OS. Among these, RPARP-AS1 was selected for in-depth investigation regarding its roles in OS proliferation and lipid metabolism. Experimental techniques including RT-qPCR, Western blot, cell viability assay, assessment, and quantification of free fatty acids (FFAs) and triglycerides (TGs) were utilized to elucidate the functional significance of RPARP-AS1 in OS cells and validate its effects on lipid metabolism. Manipulation of RPARP-AS1 expression via ectopic expression or siRNA-mediated knockdown led to alterations in epithelial-mesenchymal transition (EMT) and expression of apoptosis-associated proteins, thereby influencing OS cell proliferation and apoptosis. Mechanistically, RPARP-AS1 was found to augment the expression of key lipogenic enzymes (FABP4, MAGL, and SCD1) and potentially modulate the Akt/mTOR pathway, thereby contributing to lipid metabolism (involving alterations in FFA and TG levels) in OS cells. Collectively, our findings establish RPARP-AS1 as a novel oncogene in OS cells and suggest its role in fostering tumor growth through the enhancement of lipid metabolism.

Integrative multiomics profiling of passion fruit reveals the genetic basis for fruit color and aroma.

Passion fruit (Passiflora edulis) possesses a complex aroma and is widely grown in tropical and subtropical areas. Here, we conducted the de novo assembly, annotation, and comparison of PPF (P. edulis Sims) and YPF (P. edulis f. flavicarpa) reference genomes using PacBio, Illumina, and Hi-C technologies. Notably, we discovered evidence of recent whole-genome duplication events in P. edulis genomes. Comparative analysis revealed 7.6∼8.1 million single nucleotide polymorphisms, 1 million insertions/deletions, and over 142 Mb presence/absence variations among different P. edulis genomes. During the ripening of yellow passion fruit, metabolites related to flavor, aroma, and color were substantially accumulated or changed. Through joint analysis of genomic variations, differentially expressed genes, and accumulated metabolites, we explored candidate genes associated with flavor, aroma, and color distinctions. Flavonoid biosynthesis pathways, anthocyanin biosynthesis pathways, and related metabolites are pivotal factors affecting the coloration of passion fruit, and terpenoid metabolites accumulated more in PPF. Finally, by heterologous expression in yeast (Saccharomyces cerevisiae), we functionally characterized 12 terpene synthases. Our findings revealed that certain TPS homologs in both YPF and PPF varieties produce identical terpene products, while others yield distinct compounds or even lose their functionality. These discoveries revealed the genetic and metabolic basis of unique characteristics in aroma and flavor between the 2 passion fruit varieties. This study provides resources for better understanding the genome architecture and accelerating genetic improvement of passion fruits.

Clinical Study on Traditional Chinese Medicine Bone-Setting Manipulations Combined with Minimally-Invasive Treatment and Intramedullary Plate Fixation for the Treatment of Moderate Hallux Valgus / 广州中医药大学学报

Objective To evaluate the clinical efficacy of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus traditional Chinese medicine(TCM)bone-setting manipulations for the treatment of moderate hallux valgus.Methods A retrospective study was conducted.A total of 49 patients(62 feet)with moderate hallux valgus were treated with Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate,and were given TCM bone-setting manipulations before the operation,during the operation,and after the operation.The efficacy was evaluated by using the Visual Analogue Scale(VAS)score and the American Orthopedic Foot and Ankle Society(AOFAS)forefoot score after the operation.Before the operation and 12 months after the operation,the hallux valgus angle(HVA),intermetatarsal angle(IMA)between the first and second metatarsal bone,and the distal metatarsal articular angle(DMAA)showed by X-ray imaging in the weight-bearing position of the foot were recorded.Results(1)All of the 49 patients were followed up for 12 to 24 months,with a mean of(20.6±3.1)months.(2)The X-ray imaging assessment showed that 12 months after the operation,the mean HVA,IMA and DMAA values of the 49 patients(62 feet)were significantly lower than those before the operation,and the differences were all statistically significant(P＜0.01).(3)Twelve months after the operation,the pain VAS score of 49 patients was(3.14±1.21)points,which was significantly lower than the preoperative score points(7.26±2.52),and the difference was statistically significant(P＜0.01).(4)The assessment of joint function showed that 12 months after the operation,the scores of various AOFAS items of pain,function and hallux alignment as well as the overall AOFAS scores of 49 patients were significantly higher than those before the operation,and the differences were statistically significant(P＜0.01).(5)For the 62 feet in 49 patients,the excellent efficacy was achieved in 53 feet,good efficacy was achieved in 7 feet,and fair efficacy was achieved in 2 feet,with the fine rate of 96.77%(60/62).Conclusion For the treatment of moderate hallux valgus,the application of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus TCM bone-setting manipulations is effective on promoting the reset of hallux-metatarsophalangeal joint,restoring the balance of the joint,and maintaining the equilibrium state of the joint through postoperative rehabilitation guidance.The combined therapy exerts certain efficacy,reduces the recurrence rate,and eventually achieves the early rehabilitation after the operation.

Protective effect and mechanism of acellular nerve allografts combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury / 解剖学报

Objective To investigate the protective effect and mechanism of acellular nerve allografts(ANA)combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury(SNI).Methods Totally 50 male adult SD rats were randomly selected for this experiment.Ten rats were prepared for the ANA.Forty male SD rats were randomly divided into normal group,model group,ANA group and combinational group,with 10 rats in each group.The SNI model was established by cutting off the nerves 10 mm at the 5 mm on the inferior border of piriformis after separating the right sciatic nerves.The rats in the ANA group were bridged with ANA to the two broken ends of injured nerves.The rats in the combinational group were treated with electroacupuncture 2 days after ANA bridging,Huantiao(GB30)and Yanglingquan(GB34)were performed as the acupuncture points,each electroacupuncture lasted 15 minutes and 7 days as a course of treatment,4 courses in all.Sciatic nerve conduction velocity was measured by electrophysiology to evaluate the regeneration of damaged axons.Morphology of spinal ganglia was observed by Nissl staining.The expression of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)were detected by Western blotting and immunofluorescent staining.Results Compared with the normal group,the sciatic nerve conduction velocity in model group decreased significantly(P<0.01),Nissl bodies in neurons of spinal ganglia were swollen and dissolved,with incomplete structure and the number decreased dramatically(P<0.01),while the level of NGF and BDNF also decreased significantly(P<0.01).Compared with the model group,the sciatic nerve conduction velocity in ANA and combinational groups strongly increased(P<0.01),the damage of Nissl bodies in neurons of spinal ganglia reduced and the number obviously increased(P<0.01),the level of NGF and BDNF increased considerably(P<0.01).Compared with the ANA group,the sciatic nerve conduction velocity in combinational group increased significantly(P<0.01),the morphology of Nissl bodies in neurons of spinal ganglia were more regular and the number increased(P<0.01),moreover,the level of NGF also increased significantly(P<0.01).Conclusion ANA combined with electroacupuncture can enhance the sciatic nerve conduction velocity,improve the morphology of neurons in spinal ganglia and play a protective effect on spinal ganglia.The mechanism can be related to the higher expression of NGF and BDNF proteins,especially the expression of NGF protein.

Clinical analysis of 102 cases of labor induction in the third trimester on twin pregnancy / 中华妇产科杂志

Objective: To investigate the clinical characteristics of induced labor in twin pregnancy and the related factors of induced labor failure. Methods: The clinical data of twin pregnant women who underwent induced labor in Peking University Third Hospital from January 2016 to December 2022 were retrospectively analyzed. According to whether they had labor or not after induction, pregnant women were divided into the success group (pregnant women who had labor after induction, 72 cases) and the failure group (pregnant women who did not have labor after induction, 30 cases). Logistic regression was used to analyze the related factors of induction failure in twin pregnant women. Results: The parity and cervical Bishop score in the failure group were significantly lower than those in the success group, while the proportion of dichorionic diamniotic twins, assisted reproductive technology pregnancy and cervical Bishop score <6, postpartum hospital stay and total hospital stay in the failure group were significantly higher than those in the success group (all P<0.05). The proportion of induced labor by artificial rupture of membranes ± oxytocin intravenous infusion in the success group was 72.2% (52/72), which was significantly higher than that in the failure group (46.7%, 14/30; P=0.030). There were no significant differences between the two groups in the gestational age at delivery, the incidence of severe postpartum hemorrhage and blood transfusion, the amount of postpartum hemorrhage, the neonatal weight of two fetuses, the incidence of neonatal asphyxia, and the proportion of neonates admitted to the neonatal intensive care unit (all P>0.05). There were no severe perineal laceration and hysterectomy in all pregnant women. Multivariate logistic regression analysis showed that primipara (OR=3.064, 95%CI: 1.112-8.443; P=0.030) and cervical Bishop score <6 (OR=5.208, 95%CI: 2.008-13.508; P=0.001) were the independent risk factors for induction failure in twin pregnancy. Conclusions: Elective induction of labor in twin pregnancy is safe and feasible. It is helpful to improve the success rate of induction of labor by strictly grasping the timing and indications of termination of pregnancy, choosing the appropriate method of induction according to the condition of the cervix, and actively promoting cervical ripening .

Discussion on Effects of Electroacupuncture on Intestinal Flora and Serum Inflammation Factors in Rheumatoid Arthritis Rabbits Based on"Gut-joint"Axis / 中国中医药信息杂志

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.

Harnessing 2D Ruddlesden-Popper Perovskite with Polar Organic Cation for Ultrasensitive Multibit Nonvolatile Transistor-Type Photomemristors.

Photomemristors have been regarded as one of the most promising candidates for next-generation hardware-based neuromorphic computing due to their potentials of fast data transmission and low power consumption. However, intriguingly, so far, photomemristors seldom display truly nonvolatile memory characteristics with high light sensitivity. Herein, we demonstrate ultrasensitive photomemristors utilizing two-dimensional (2D) Ruddlesden-Popper (RP) perovskites with a highly polar donor-acceptor-type push-pull organic cation, 4-(5-(2-aminoethyl)thiophen-2-yl)benzonitrile+ (EATPCN+), as charge-trapping layers. High linearity and almost zero-decay retention are observed in (EATPCN)2PbI4 devices, which are very distinct from that of the traditional 2D RP perovskite devices consisting of nonpolar organic cations, such as phenethylamine+ (PEA+) and octylamine+ (OA+), and traditional 3D perovskite devices consisting of methylamine+ (MA+). The 2-fold advantages, including desirable spatial crystal arrangement and engineered energetic band alignment, clarify the mechanism of superior performance in (EATPCN)2PbI4 devices. The optimized (EATPCN)2PbI4 photomemristor also shows a memory window of 87.9 V and an on/off ratio of 106 with a retention time of at least 2.4 × 105 s and remains unchanged after >105 writing-reading-erasing-reading endurance cycles. Very low energy consumptions of 1.12 and 6 fJ for both light stimulation and the reading process of each status update are also demonstrated. The extremely low power consumption and high photoresponsivity were simultaneously achieved. The high photosensitivity surpasses that of a state-of-the-art commercial pulse energy meter by several orders of magnitude. With their outstanding linearity and retention, rabbit images have been rebuilt by (EATPCN)2PbI4 photomemristors, which truthfully render the image without fading over time. Finally, by utilizing the powerful ∼8 bits of nonvolatile potentiation and depression levels of (EATPCN)2PbI4 photomemristors, the accuracies of the recognition tasks of CIFAR-10 image classification and MNIST handwritten digit classification have reached 89% and 94.8%, respectively. This study represents the first report of utilizing a functional donor-acceptor type of organic cation in 2D RP perovskites for high-performance photomemristors with characteristics that are not found in current halide perovskites.

Dose-response association of benzodiazepine use and development of deep vein thrombosis.

Benzodiazepines have sedative effects that cause reduced activity in users and may increase the risk of deep vein thrombosis. However, few studies have examined this potential risk of benzodiazepine use. This study examined the association between benzodiazepine use and the risk of deep vein thrombosis (DVT) in adults in Taiwan using a longitudinal health insurance database. The study population included 12,546 individuals with DVT and 50,184 matched controls. Results showed that benzodiazepine use was associated with an increased risk of DVT occurrence (adjusted odds ratio [aOR]: 1.66; 95 % CI, 1.54-1.79; P <0.001), with a dose-response relationship. Patients with a higher defined daily dose had a higher risk of DVT, with ORs of 1.65-, 2.09-, and 2.16-fold higher for those with an average benzodiazepine dose of <0.5, 0.5-0.9, or ≥1 (DDD/day), respectively, compared to nonbenzodiazepine users. Stratification by age, sex, and follow-up duration yielded similar results. This study highlights the need to evaluate the association and benefits of benzodiazepine prescription to decrease the risk of DVT development.

Intratumoral injection of norcantharidin liposome emulsion hybrid delivery system amplifies the cancer-fighting effects of oral sorafenib against hepatocellular carcinoma.

Interventional therapies are increasingly used in clinical trials for hepatocellular carcinoma (HCC). Sorafenib is the front-line remedy for HCC, however, chemoresistance occurs immutably and affects the effectiveness of treatment. In a previous study, a norcantharidin liposome emulsion hybrid (NLEH) delivery system for HCC was developed. This study aims to examine the therapeutic effects of the combination of intratumoral injection of NLEH and sorafenib in treating HCC. Sorafenib combined with NLEH activated the apoptosis pathway by synergistically upregulating caspase-9, promoting cytotoxicity, apoptosis (64.57%), and G2/M cell cycle arrest (48.96%). Norcantharidin could alleviate sorafenib resistance by counteracting sorafenib-induced phosphorylation of Akt. Additionally, intratumoral injection of NLEH exhibited a sustained accumulation in the tumor within 24 h and didn't distribute to other major organs. Intratumoral injection of NLEH in combination with oral sorafenib displayed the most potent tumor growth inhibitory effect (77.91%) in vivo. H&E staining results and the indicators of the renal and liver function tests demonstrated the safety of this combination therapy. Overall, these results showed that intratumoral injection of NLEH in combination with oral sorafenib treatment represented a rational potential therapeutic option for HCC.

Recombinant Neorudin for the Prevention of Deep-Vein Thrombosis After Spinal-Cord Injury.

Background: Whether anticoagulant therapy should be used after spinal-cord injury (SCI) surgery was controversial. The anticoagulation characteristics of a newly developed anticoagulant, recombinant neorudin (EPR-hirudin (EH)), were explored using a rat model of SCI to provide a basis for clinical anticoagulation therapy of SCI. Methods: A rat model of SCI was developed by Allen's method. Then, thrombosis in the inferior vena cava was induced by ligation. The low-bleeding characteristics of EH were explored by investigating dose-response and time-effect relationships, as well as multiple administration of EH, on thrombus formation complicated with SCI. Results: EH inhibited thrombosis in a dose-dependent manner by reducing the wet weight and dry weight of the thrombus. An inhibiting action of EH on thrombosis was most evident in the group given EH 2 h after SCI. After multiple intravenous doses of EH, thrombosis inhibition was improved to that observed with low molecular weight heparin (LMWH) (87% vs 90%). EH administration after SCI neither increased bleeding in the injured spine nor damaged to nerve function. Bleeding duration and activated partial thromboplastin time were increased in the high-dose EH group compared with that in the normal-saline group, but were lower than those in the LMWH group. Conclusion: EH can reduce thrombus formation in a rat model of SCI, and bleeding is decreased significantly compared with that using LMWH. EH may prevent thrombosis after SCI or spinal surgery.

Prediction of intraoperative cerebrospinal fluid leaks in endoscopic endonasal transsphenoidal pituitary surgery based on a deep neural network model trained with MRI images: a pilot study.

Objective: This study aimed to investigate the reliability of a deep neural network (DNN) model trained only on contrast-enhanced T1 (T1CE) images for predicting intraoperative cerebrospinal fluid (ioCSF) leaks in endoscopic transsphenoidal surgery (EETS). Methods: 396 pituitary adenoma (PA) cases were reviewed, only primary PAs with Hardy suprasellar Stages A, B, and C were included in this study. The T1CE images of these patients were collected, and sagittal and coronal T1CE slices were selected for training the DNN model. The model performance was evaluated and tested, and its interpretability was explored. Results: A total of 102 PA cases were enrolled in this study, 51 from the ioCSF leakage group, and 51 from the non-ioCSF leakage group. 306 sagittal and 306 coronal T1CE slices were collected as the original dataset, and data augmentation was applied before model training and testing. In the test dataset, the DNN model provided a single-slice prediction accuracy of 97.29%, a sensitivity of 98.25%, and a specificity of 96.35%. In clinical test, the accuracy of the DNN model in predicting ioCSF leaks in patients reached 84.6%. The feature maps of the model were visualized and the regions of interest for prediction were the tumor roof and suprasellar region. Conclusion: In this study, the DNN model could predict ioCSF leaks based on preoperative T1CE images, especially in PAs in Hardy Stages A, B, and C. The region of interest in the model prediction-making process is similar to that of humans. DNN models trained with preoperative MRI images may provide a novel tool for predicting ioCSF leak risk for PA patients.

Effect of a moderate-intensity comprehensive exercise program on body composition, muscle strength, and physical performance in elderly females with sarcopenia.

Objective: This study aimed at examining an eight-week moderate-intensity comprehensive exercise training program on the parameters of sarcopenia in elderly females. Methods: A total of 49 community-dwelling elderly females with sarcopenia (65.5 ± 2.5) were assigned randomly to an experiment group (EG, n = 25) and a control group (CG, n = 24). In the EG, an eight-week comprehensive exercise training program was implemented, in 1 h, 3 times per week, a total of 24 sessions. The CG only received health public education per two weeks, a total of 4 times. Subsequently, the differences between the two groups were tested through two-way repeated ANOVA. Results: ASM, SMM, and SMI in the EG were significantly improved by 0.26 kg, 0.18 kg, and 0.10 kg/m2, respectively. Group-by-time interactions were significantly different on the ASM [F (1,47) = 6.25, η2 = 0.12] and SMI [F (1,47) = 6.77, η2 = 0.13]. Muscle strength was improved 0.8 kg in the EG. Significant group-by-time interaction differences were reported in the handgrip strength [F (1,47) = 6.8, η2 = 0.13] after the eight-week intervention. Compared with the baseline, gait speed was improved a 0.05 m/s and 5-time chair stand was decreased a 0.27 s in the EG. Group-by-time interactions were significantly different in 5-time chair stand [F (1, 47) = 6.35, η2 = 0.12]. Conclusions: The moderate-intensity comprehensive exercise was confirmed as a safe and convenient exercise program. Although a load of training intensity is not sufficient to improve the gait speed, this exercise protocol is promising in delaying overall results in community-dwelling sarcopenia elderly females and contributes to the improvement of muscle mass, handgrip strength, and 5TCS.