Mechanism of phosphate release from actin filaments.

After ATP-actin monomers assemble filaments, the ATP's [Formula: see text]-phosphate is hydrolyzedwithin seconds and dissociates over minutes. We used all-atom molecular dynamics simulations to sample the release of phosphate from filaments and study residues that gate release. Dissociation of phosphate from Mg2+ is rate limiting and associated with an energy barrier of 20 kcal/mol, consistent with experimental rates of phosphate release. Phosphate then diffuses within an internal cavity toward a gate formed by R177, as suggested in prior computational studies and cryo-EM structures. The gate is closed when R177 hydrogen bonds with N111 and is open when R177 forms a salt bridge with D179. Most of the time, interactions of R177 with other residues occlude the phosphate release pathway. Machine learning analysis reveals that the occluding interactions fluctuate rapidly, underscoring the secondary role of backdoor gate opening in Pi release, in contrast with the previous hypothesis that gate opening is the primary event.

Skin-inspired, sensory robots for electronic implants.

Drawing inspiration from cohesive integration of skeletal muscles and sensory skins in vertebrate animals, we present a design strategy of soft robots, primarily consisting of an electronic skin (e-skin) and an artificial muscle. These robots integrate multifunctional sensing and on-demand actuation into a biocompatible platform using an in-situ solution-based method. They feature biomimetic designs that enable adaptive motions and stress-free contact with tissues, supported by a battery-free wireless module for untethered operation. Demonstrations range from a robotic cuff for detecting blood pressure, to a robotic gripper for tracking bladder volume, an ingestible robot for pH sensing and on-site drug delivery, and a robotic patch for quantifying cardiac function and delivering electrotherapy, highlighting the application versatilities and potentials of the bio-inspired soft robots. Our designs establish a universal strategy with a broad range of sensing and responsive materials, to form integrated soft robots for medical technology and beyond.

Exogenous sulfide regulates hypoxia/reoxygenation stress through the intrinsic apoptotic pathway in the blood clam (Tegillarca granosa).

The intertidal organism Tegillarca granosa can survive under frequent hypoxia/reoxygenation (H/R) exposure. Sulfides as accompanying products in benthic hypoxic environments, may play an important regulatory role, but the mechanisms are not well understood. This article investigated the physiological and molecular changes of T. granosa after adding different concentrations of sulfides (0.1, 0.5, 1 mM) at 72 h into a 120-h exposure to hypoxia, as well as the recovery state of 24 h of reoxygenation. The results indicated that H/R stress induces ROS production and mild mitochondrial depolarization in clams, and sulfide can participate in its regulation. Among them, a low concentration of sulfide up-regulated glutathione content and alternative oxidase activity, maintained the stability of antioxidant enzymes, and up-regulated the expression of the survival genes XIAP/BCL-xl which mediate cell survival via the NFκB signaling pathway. High concentrations of sulfide had a significant inhibitory effect on the p38/MPAK pathway and inhibited intrinsic apoptosis caused by ROS accumulation during reoxygenation. Taken together, our study suggested that different concentrations of sulfides are involved in regulating the endogenous apoptosis of clams during H/R.

Distinctive hydrodynamic properties and ecological responses of multi-thread rivers under different degrees of multiplicity in the Upper Yellow River.

Alluvial rivers that exhibit multi-thread patterns are common in nature and can be the dominant channel morphology in large rivers. However, their ecological properties in response to diverse and dynamic channel morphology has gained limited attention and remained poorly understood. In this study, we adopted an eco-hydraulic model by integrating a hydrodynamic, a sediment-transport, and a habitat-suitability model to assess habitat quality for fish species (Schizopygopsis pylzovi and Platypharodon extremus) in three anabranching reaches with each exhibiting a distinct anabranching morphology in the Upper Yellow River, eastern Qinghai-Tibet Plateau. Based on the hydrologic data and actual channel morphology, we modeled the hydrodynamic and sediment-transport conditions for a period spanning ten years, and simulated habitat conditions under a potentially changing environment with different flow magnitudes and frequencies. The results indicated that the average flow velocity in the low and mid-order anabranching reaches is higher than that in the high-order, complex anabranching reaches. Meanwhile, the bedload transport rate was higher in the high and mid-order anabranching reaches than that in the low-order anabranching reach, demonstrating a greater transport efficiency of multi-thread systems with a greater multiplicity. Consequently, the habitat suitability shows a deteriorating trend over the ten-year modeling period and Schizopygopsis pylzovi shows better habitat status than Platypharodon extremus. The flow magnitudes and frequency also have a significant impact on the distribution of high habitat suitability index among the different river patterns in Upper Yellow River. This study can provide valuable information to optimize ecological outcomes and provide valuable insights for future dam operation strategies and consideration efforts aimed at preserving and restoring riverine ecosystems.

Biological impact and therapeutic potential of a novel camptothecin derivative (FLQY2) in pancreatic cancer through inactivation of the PDK1/AKT/mTOR pathway.

BACKGROUND: Camptothecin (CPT), a pentacyclic alkaloid with antitumor properties, is derived from the Camptotheca acuminata. Topotecan and irinotecan (CPT derivatives) were first approved by the Food and Drug Administration for cancer treatment over 25 years ago and remain key anticancer drugs today. However, their use is often limited by clinical toxicity. Despite extensive development efforts, many of these derivatives have not succeeded clinically, particularly in their effectiveness against pancreatic cancer which remains modest. AIM OF THE STUDY: This study aimed to evaluate the therapeutic activity of FLQY2, a CPT derivative synthesized in our laboratory, against pancreatic cancer, comparing its efficacy and mechanism of action with those of established clinical drugs. METHODS: The cytotoxic effects of FLQY2 on cancer cells were assessed using an MTT assay. Patient-derived organoid (PDO) models were employed to compare the sensitivity of FLQY2 to existing clinical drugs across various cancers. The impact of FLQY2 on apoptosis and cell cycle arrest in Mia Paca-2 pancreatic cancer cells was examined through flow cytometry. Transcriptomic and proteomic analyses were conducted to explore the underlying mechanisms of FLQY2's antitumor activity. Western blotting was used to determine the levels of proteins regulated by FLQY2. Additionally, the antitumor efficacy of FLQY2 in vivo was evaluated in a pancreatic cancer xenograft model. RESULTS: FLQY2 demonstrated (1) potent cytotoxicity; (2) superior tumor-suppressive activity in PDO models compared to current clinical drugs such as gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, ivosidenib, infinitinib, and lenvatinib; (3) significantly greater tumor inhibition than paclitaxel liposomes in a pancreatic cancer xenograft model; (4) robust antitumor effects, closely associated with the inhibition of the TOP I and PDK1/AKT/mTOR signaling pathways. In vitro studies revealed that FLQY2 inhibited cell proliferation, colony formation, induced apoptosis, and caused cell cycle arrest at nanomolar concentrations. Furthermore, the combination of FLQY2 and gemcitabine exhibited significant inhibitory and synergistic effects. CONCLUSION: The study confirmed the involvement of topoisomerase I and the PDK1/AKT/mTOR pathways in mediating the antitumor activity of FLQY2 in treating Mia Paca-2 pancreatic cancer. Therefore, FLQY2 has potential as a novel therapeutic option for patients with pancreatic cancer.

[Evaluation of chemical constituents of Draconis Sanguis and its protective effect on renal tubular injury in diabetic kidney disease].

The chemical constituents of Draconis Sanguis were preliminarily studied by macroporous resin, silica gel, dextran gel, and high-performance liquid chromatography. One retro-dihydrochalcone, four flavonoids, and one stilbene were isolated. Their chemical structures were identified as 4-hydroxy-2,6-dimethoxy-3-methyldihydrochalcone(1), 4'-hydroxy-5,7-dimethoxy-8-methylflavan(2), 7-hydroxy-4',5-dimethoxyflavan(3),(2S)-7-hydroxy-5-methoxy-6-methylflavan(4),(2S)-7-hydroxy-5-methoxyflavan(5), and pterostilbene(6) by modern spectroscopy, physicochemical properties, and literature comparison. Compound 1 was a new compound. Compounds 2 and 6 were first found in the Arecaceae family. Compound 5 had the potential to prevent and treat diabetic kidney disease.

From Latent Dynamics to Meaningful Representations.

While representation learning has been central to the rise of machine learning and artificial intelligence, a key problem remains in making the learned representations meaningful. For this, the typical approach is to regularize the learned representation through prior probability distributions. However, such priors are usually unavailable or are ad hoc. To deal with this, recent efforts have shifted toward leveraging the insights from physical principles to guide the learning process. In this spirit, we propose a purely dynamics-constrained representation learning framework. Instead of relying on predefined probabilities, we restrict the latent representation to follow overdamped Langevin dynamics with a learnable transition density─a prior driven by statistical mechanics. We show that this is a more natural constraint for representation learning in stochastic dynamical systems, with the crucial ability to uniquely identify the ground truth representation. We validate our framework for different systems including a real-world fluorescent DNA movie data set. We show that our algorithm can uniquely identify orthogonal, isometric, and meaningful latent representations.

Effectiveness of Yijinjing exercise in the treatment of early-stage knee osteoarthritis: a randomized controlled trial protocol.

INTRODUCTION: Knee osteoarthritis (KOA) is still a challenging degenerative joint disease with high morbidity and disease burden. Early-stage KOA, the focus of this study, could present a Window of Opportunity to arrest the disease process and reduce the disease burden. Yijinjing exercise is an important part of physical and psychological therapies in Traditional Chinese Exercise and may be an effective treatment. However, there is no clinical efficacy assessment of Yijinjing exercise for patients with early-stage KOA. Therefore, we designed a randomised controlled trial to evaluate the effectiveness of Yijinjing exercise on patients with early-stage KOA. METHODS AND ANALYSIS: This is a parallel-design, two-arm, analyst assessor-blinded, randomised controlled trial. In total, 60 patients with early-stage KOA will be recruited and randomly assigned to the Yijinjing exercise group (n=30) and health education group (n=30) at a ratio of 1:1, receiving 12 weeks of Yijinjing exercise or health education accordingly. The primary outcome will be measured with the Western Ontario and McMaster Universities Osteoarthritis Index, and the secondary outcomes will include the Visual Analogue Scale, Short-Form 36 Item Health Survey Questionnaire, Beck Depression Inventory, Perceived Stress Scale, Berg Balance Scale, and Gait Analysis for a comprehensive assessment. Outcome measures are collected at baseline, at 12 week ending intervention and at the 12 week, 24 week and 48 week ending follow-up. The primay time point will be 12 weeks postintervention. Adverse events will be recorded for safety assessment. ETHICS AND DISSEMINATION: This study has been approved by the ethical application of the Shanghai Municipal Hospital of Traditional Chinese Medicine Ethics Committee (2021SHL-KY-78). TRIAL REGISTRATION NUMBER: ChiCTR2200065178.

Parental Depression and Self-Stigma Among Chinese Young People Living With Depression: A Qualitative Study.

Self-stigma is detrimental to psychosocial well-being and the recovery journey among people living with depression. However, there has been limited research exploring the experience of stigma internalization when depression runs in families. This study aims to address this gap by (1) characterizing the manifestations of self-stigma among individuals living with depression whose parent(s) also have depression and (2) exploring the potential mechanisms underlying the impact of parental depression on self-stigma. Essential principles of the constructivist grounded theory approach were adopted to collect data through in-depth interviews with 27 participants aged 15-30, living in Mainland China. Many participants perceived depression running in their family as an endless disaster and an incurable illness. These beliefs further led to stigmatizing emotions (such as suppression, anger, and guilt) and behaviors (such as concealment and social withdrawal). Participants also highlighted ambivalent intergenerational relationships, tense family atmospheres, lower parental emotional involvement and support, and a lack of family flexibility due to parental depression. Furthermore, parental depression impacted participants' self-stigma by interfering with family relationships, family functioning, and parenting styles. It also shaped their perceptions of family, illness attribution, and public stigma. Additionally, parental depression had an impact on participants' social functioning, self-esteem, and personality, making them more susceptible to self-stigma. This study emphasizes the crucial role that the family plays in the internalization of stigma among individuals living with depression. It suggests that family dynamics, rather than family structure or economic backgrounds alone, shape this process.

The effect of omentoplasty in various surgical operations: systematic review and meta-analysis.

BACKGROUND: Omentoplasty is commonly used in various surgeries. However, its effectiveness is unsure due to lack of convincing data and research. To clarify the impact of omentoplasty on postoperative complications of various procedures, this systematic review and meta-analysis was performed. METHODS: A systematic review of published literatures from four databases: PubMed, Web of Science, Cochrane Library, and Embase before 14 July 2022. The authors primarily included publications on five major surgical operations performed in conjunction with omentoplasty: thoracic surgery, esophageal surgery, gastrointestinal surgery, pelvi-perineal surgery, and liver surgery. The protocol was registered in PROSPERO. RESULTS: This review included 25 273 patients from 91 studies ( n =9670 underwent omentoplasty). Omentoplasty was associated with a lower risk of overall complications particularly in gastrointestinal [relative risk (RR) 0.53; 95% CI: 0.39-0.72] and liver surgery (RR 0.54; 95% CI: 0.39-0.74). Omentoplasty reduced the risk of postoperative infection in thoracic (RR 0.38; 95% CI: 0.18-0.78) and liver surgery (RR 0.39; 95% CI: 0.29-0.52). In patients undergoing esophageal (RR 0.89; 95% CI: 0.80-0.99) and gastrointestinal (RR 0.28; 95% CI: 0.23-0.34) surgery with a BMI greater than 25, omentoplasty is significantly associated with a reduced risk of overall complications compared to patients with normal BMI. No significant differences were found in pelvi-perineal surgery, except infection in patients whose BMI ranged from 25 kg/m 2 to 29.9 kg/m 2 (RR 1.25; 95% CI: 1.04-1.50) and anastomotic leakage in patients aged over 60 (RR 0.59; 95% CI: 0.39-0.91). CONCLUSION: Omentoplasty can effectively prevent postoperative infection. It is associated with a lower incidence of multiple postoperative complications in gastrointestinal and liver surgery.

Multi-contrast learning-guided lightweight few-shot learning scheme for predicting breast cancer molecular subtypes.

Invasive gene expression profiling studies have exposed prognostically significant breast cancer subtypes: normal-like, luminal, HER-2 enriched, and basal-like, which is defined in large part by human epidermal growth factor receptor 2 (HER-2), progesterone receptor (PR), and estrogen receptor (ER). However, while dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been generally employed in the screening and therapy of breast cancer, there is a challenging problem to noninvasively predict breast cancer molecular subtypes, which have extremely low-data regimes. In this paper, a novel few-shot learning scheme, which combines lightweight contrastive convolutional neural network (LC-CNN) and multi-contrast learning strategy (MCLS), is worthwhile to be developed for predicting molecular subtype of breast cancer in DCE-MRI. Moreover, MCLS is designed to construct One-vs-Rest and One-vs-One classification tasks, which addresses inter-class similarity among normal-like, luminal, HER-2 enriched, and basal-like. Extensive experiments demonstrate the superiority of our proposed scheme over state-of-the-art methods. Furthermore, our scheme is able to achieve competitive results on few samples due to joint LC-CNN and MCLS for excavating contrastive correlations of a pair of DCE-MRI.

Transcriptional and physiological profiles reveal the respiratory, antioxidant and metabolic adaption to intermittent hypoxia in the clam Tegillarca granosa.

Tegillarca granosa can survive intermittent hypoxia for a long-term. We used the clam T. granosa as model to investigate the respiratory, antioxidant and metabolic responses to consecutive hypoxia-reoxygenation (H/R) stress at both physiological and transcriptional levels. The results showed that the clams were able to rapidly regulate oxygen consumption and ammonia excretion during H/R stress, and alleviate oxidative stress during the second-time challenge. The clams also efficiently balanced energy metabolism through the rapid conversion and decomposition of glycogen. According to the transcriptome profile, KEGG pathways of starch and sucrose metabolism, ECM-receptor interaction, and protein processing in endoplasmic reticulum were significantly enriched in H group (the second-time 24 h hypoxia exposure), while pathways associated with lipid metabolism were significantly enriched in h group (the first-time 24 h hypoxia exposure). DEGs including hspa5, birc2/3, and map3k5 might play important roles in alleviating endoplasmic reticulum stress, cpla2 and pla2g16 might mitigate oxidative stress by adjusting the composition of cellular membrane. In conclusions, our findings suggest that rapid adjustment of oxygen consumption, ammonia metabolism, glycogen metabolism, and the ability to adjust the composition of the membrane lipid may be critical for T. granosa in maintaining energy homeostasis and reducing oxidative damage during intermittent H/R exposure. This study preliminarily clarified the response of T. granosa to intermittent hypoxia stress on the physiological and molecular levels, offering insights into the hypoxia-tolerant mechanisms in this species and providing a reference for the following study on the other hypoxic-tolerant species.

Research Review: Grandparental care and child mental health - a systematic review and meta-analysis.

BACKGROUND: The number of children residing in grandfamilies is growing worldwide, leading to more research attention on grandparental care over the past decades. Grandparental care can influence child well-being in various forms and the effects vary across contexts. In this systematic review and meta-analysis, we synthesize the evidence on the relation between grandparental care and children's mental health status. METHODS: We identified 5,745 records from seven databases, among which 38 articles were included for review. Random effects meta-analyses were used to synthesize evidence from eligible studies. We also examined the variability across study and participant characteristics, including study design, recruitment method, child age, child gender, study region, family type, comparison group, and outcome rater. RESULTS: The meta-analysis consisted of 344,860 children from the included studies, whose average age was 10.29, and of which 51.39% were female. Compared with their counterparts, children being cared for by their grandparents had worse mental health status, including more internalizing problems (d = -0.20, 95% CI [-0.31, -0.09], p = .001), externalizing problems (d = -0.11, 95% CI [-0.21, -0.01], p = .03), overall mental problems (d = -0.37, 95% CI [-0.70, -0.04], p = .03), and poorer socioemotional well-being (d = -0.26, 95% CI [-0.49, -0.03], p = .03). The effects varied by study design and child gender. CONCLUSIONS: The findings highlight that grandparental care is negatively associated with child mental health outcomes with trivial-to-small effect sizes. More supportive programs and interventions should be delivered to grandfamilies, especially in disadvantaged communities.

Digital automation of transdermal drug delivery with high spatiotemporal resolution.

Transdermal drug delivery is of vital importance for medical treatments. However, user adherence to long-term repetitive drug delivery poses a grand challenge. Furthermore, the dynamic and unpredictable disease progression demands a pharmaceutical treatment that can be actively controlled in real-time to ensure medical precision and personalization. Here, we report a spatiotemporal on-demand patch (SOP) that integrates drug-loaded microneedles with biocompatible metallic membranes to enable electrically triggered active control of drug release. Precise control of drug release to targeted locations (<1 mm2), rapid drug release response to electrical triggers (<30 s), and multi-modal operation involving both drug release and electrical stimulation highlight the novelty. Solution-based fabrication ensures high customizability and scalability to tailor the SOP for various pharmaceutical needs. The wireless-powered and digital-controlled SOP demonstrates great promise in achieving full automation of drug delivery, improving user adherence while ensuring medical precision. Based on these characteristics, we utilized SOPs in sleep studies. We revealed that programmed release of exogenous melatonin from SOPs improve sleep of mice, indicating potential values for basic research and clinical treatments.

Old trees bloom new flowers, lysosome targeted near-infrared fluorescent probe for ratiometric sensing of hypobromous acid in vitro and in vivo based on Nile red skeleton.

Hypobromous acid (HOBr), one of the significant reactive oxygen species (ROS) that acts as an important role in human immune system, however the increasing level of HOBr in human body can cause the disorder of eosinophils (EPO), leading to oxidative stress in organelles, and further causing a series of diseases. In this study, a ratiometric fluorescent probe DMBP based on Nile red skeleton was developed to detect HOBr specifically by the electrophilic substitution with HOBr. DMBP emits near-infrared (NIR) fluorescence at 653 nm, after reacting with HOBr, the emission wavelength of DMBP shifted blue and a new peak appeared at 520 nm, realizing a ratiometric examination of HOBr with a limit of detection of 89.00 nM. Based on its sensitive and specific response to HOBr, DMBP was applied in the visual imaging of HOBr in HepG2 cells and zebrafish. Foremost, probe DMBP has excellent lysosome targeting ability and NIR emission reduced the background interference of biological tissues, providing a potential analytical tool to further investigate the role of HOBr in lysosome.

Mechanism of Phosphate Release from Actin Filaments.

After ATP-actin monomers assemble filaments, the γ-phosphate is hydrolyzed from ATP within seconds and dissociates from the filament over several minutes. We used all-atom well-tempered metadynamics molecular dynamics simulations to sample the release of phosphate from filaments along with unbiased molecular dynamics simulations to study residues that gate release. Dissociation of phosphate from Mg2+ is rate limiting and associated with an energy barrier of 20 kcal/mol, consistent with experimental rates of phosphate release. Phosphate then diffuses in an internal cavity toward a gate formed by R177 suggested in prior computational studies and cryo-EM structures. The gate is closed when R177 hydrogen bonds with N111 and is open when R177 forms a salt bridge with D179. Most of the time interactions of R177 with other residues occludes the phosphate release pathway. Machine learning analysis reveals that the occluding interactions fluctuate rapidly. These occluded states have not been documented in cryo-EM reconstructions.

Impacts of the Three Gorges Dam on riparian vegetation in the Yangtze River Basin under climate change.

As the largest hydroelectric project in the world, the Three Gorges Dam (TGD) is expected to have significant environmental and ecological impacts on riparian vegetation in the Yangtze River Basin (YRB). However, existing studies have mainly focused on small segments of the YRB. In addition, few studies have quantified the responses of riparian vegetation to both climatic factors and dam construction. In this study, we investigated riparian vegetation dynamics over the entire YRB before, during, and after the construction of TGD from 1982 to 2015 using the normalized difference vegetation index (NDVI). Furthermore, the effects of climatic factors and dam construction on riparian vegetation were quantitatively analyzed using path analysis. The results demonstrate that the YRB has experienced a generally greening trend after TGD construction. The impacts of climate change on riparian vegetation have exhibited notable spatial heterogeneity and temperature is the main climatic factor that affects riparian vegetation growth. Moreover, TGD becomes the major contributor to riparian vegetation dynamics in the YRB after TGD construction. TGD has not only directly enhanced riparian vegetation but also indirectly affected riparian vegetation by regulating the microclimate. This study highlights the significance of anthropogenic interference when evaluating the relationships between riparian vegetation and climatic factors, providing useful insights for the effective management and conservation of large-scale riparian ecosystems.

The effects of ketamine and methamphetamine on neurotransmitters, glutamate receptors, and conditioned place preference in rat.

Combined methamphetamine (MA) and ketamine (KET) abuse is a serious issue. At present, however, few studies have explored the mechanism underlying their combined addiction. We established a rat conditioned place preference (CPP) model. We investigated the role of dopamine (DA), 5-hydroxytryptamine (5-HT), monoamine oxidase (MAO), glutamate receptor 1 (GluR1), and glutamate receptor 2 (GluR2) in combined MA and KET addiction. The expression levels of DA, 5-HT, and MAO were detected by enzyme-linked immunosorbent assay (ELISA), and the expressions levels of GluR1 and GluR2 were detected by western blotting. Our results showed that MA and KET successfully induced CPP in rats respectively, and KET enhanced MA-induced CPP effects, although not significantly, and KET can reduce the MA-induced increase in DA, 5-HT, MAO and promoted the MA-induced increase in GluR1 and GluR2. Therefore, it suggested that DA, 5-HT, MAO, GluR1, and GluR2 expression may be involved in the mechanism underlying MA and KET-induced drug addiction in rats. Moreover, When MA and KET are used in combination, KET appears to play a dual addictive and anti-addictive role in the regulation of MA addiction.

Efficacy of extracts from Datura Metel L. for Psoriasis: a meta-analysis of case series and single-arm studies.

BACKGROUND: Datura Metel L. has been used to treat psoriasis in China for a long time. The effect of extracts from Datura Metel L. for Psoriasis has not been previously confirmed. This study aimed to evaluate the efficacy of extracts from Datura Metel L. for patients with psoriasis. METHODS: PubMed, Cochrane Library, Embase, and other databases were searched from database inception until to September 1, 2021. A quality assessment and data extraction were performed by 2 independent reviews. We used a random-effects meta-analysis model to estimate the pooled curative effect, pooled odds ratio (OR), and 95% confidence intervals. RESULTS: Nine studies were included in Meta-analysis, including a total number of 1778 patients with psoriasis. The case cure rate of Datura Metel L. intravenous therapy was 0.48 (95% CI: 0.33, 0.62) and of Datura Metel L. oral therapy was 0.42 (95% CI: 0.17, 0.68), respectively. The case effective rate of Datura Metel L. intravenous therapy was 0.91 (95% CI: 0.84, 0.97) and of Datura Metel L. oral therapy was 0.94 (95% CI: 0.88, 0.99), respectively. CONCLUSIONS: The extracts from Datura Metel L. showed the potential to treat psoriasis, and intravenous therapy might be a promising treatment to cure psoriasis, which is likely affected by selection and publication bias, still need more high quality clinical studies.

Analysis of a new therapeutic target and construction of a prognostic model for breast cancer based on ferroptosis genes.

Breast cancer, which is the most common malignant tumor among women worldwide and an important cause of death in women. The existing prognostic model for patients with breast cancer is not accurate as breast cancer is resistant to commonly used antitumor drugs. Ferroptosis is a novel mechanism of programmed cell death that depends on iron accumulation and lipid peroxidation. Various studies have confirmed the role of ferroptosis in tumor regulation and ferroptosis is now considered to play an important role in breast cancer development. At present, the association between breast cancer prognosis and ferroptosis-related gene expression remains unclear. Further exploration of this research area may optimize the evaluation and prediction of prognosis of patients with breast cancer and finding of new therapeutic targets. In this study, clinical factors and the expression of multiple genes were evaluated in breast cancer samples from the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database database. Eleven prognostication-related genes (TP63, IFNG, MT3, ANO6, FLT3, PTGS2, SLC1A4, JUN, SLC7A5, CHAC1, and TF) were identified from differentially expressed genes to construct a survival prediction model, which showed a good prediction ability. KEGG pathway analysis revealed that immune-related pathways were the primary pathways. ssGSEA analysis showed significant differences in the distribution of certain immune-related cell subsets, such as CD8+T cells and B cells, and in the expression of multiple immune genes, including type II IFN response and APC coinhibition. In addition, 10 immune targets related to ferroptosis in breast cancer were found: CD276, CD80, HHLA2, LILRA2, NCR3LG1, NECTIN3, PVR, SLAMF9,TNFSF4, and BTN1A1. Using TCGA, new ferroptosis genes related to breast cancer prognosis were identified, a new reliable and accurate prognosis model was developed, and 10 new potential therapeutic targets different from the traditional targeted drugs were identified to provide a reference for improving the poor prognosis of patients with breast cancer.