Illuminating the fight against breast cancer: Preparation and visualized photothermal therapy of hyaluronic acid coated ZIF-8 loading with indocyanine green and cryptotanshinone for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is characterized by higher recurrence rate and mortality. Thermally-mediated ablation via photothermal therapy (PTT) demonstrates considerable promise for the eradication of breast cancer. Nonetheless, the efficacy of PTT is impeded by the thermal tolerance of tumor cells, which is attributed to the augmented expression of heat shock proteins (HSPs). These proteins, which function as ATP-dependent molecular chaperones, confer protection to cancer cells against the cytotoxic heat generated during PTT. Glycolysis is an important way for breast cancer cells to produce ATP, which can promote the occurrence and development of lung metastasis of breast cancer. Therefore, inhibiting glycolysis may diminish the expression of HSPs, curtail the growth of breast cancer, and prevent its metastasis. Glycolytic metabolism plays a pivotal role in the ATP biosynthesis within breast cancer cells, facilitating the progression and dissemination of pulmonary metastases. Consequently, targeting glycolysis presents a strategic approach to HSP expression, the proliferation of breast cancer, and impede its metastatic spread. Herein, we designed an indocyanine green (ICG) and cryptotanshinone (CTS) loaded hyaluronic acid (HA) coated Zeolitic Imidazolate Framework-8 (ZIF-8) drug delivery system. The drug delivery system had excellent photothermal properties, which could reach temperature sufficient for photothermal ablation of tumor cells. (ICG + CTS)@HA-ZIF-8 also showed pH-responsive drug release, enhancing the sustained release of ICG and CTS to extend their systemic circulation duration. Moreover, the HA modification of ZIF-8 served to augment its targeting capabilities both in vitro and in vivo, leveraging the enhanced permeation and retention (EPR) effect, as well as active tumor targeting via the CD44 receptor pathway, resulting in a higher drug concentration and a better therapeutic effect in tumor. (ICG + CTS)@HA-ZIF-8 could downregulate the expression of glycolysis-related protein pyruvate kinase-M2 (PKM2), thereby inhibiting the glycolysis process, further suppressing tumor cell energy metabolism, downregulating the expression of HSPs, overcoming tumor cell heat resistance, and improving PTT effect. It exhibited a notable suppressive impact on both the proliferation and migration of breast cancer cells, potentially offering innovative insights for the visualized PTT in breast cancer treatment.

In-situ electrospinning PVB/Camellia oil/ZnO-TiO2 nanofibrous membranes with synergistic antibacterial and degradation of ethylene applied in fruit preservation.

This work utilizes a handheld electrospinning device to prepare a novel nanofibrous composite membrane in situ for packaging freshness. It can realize pick-and-pack and is easy to operate. The nanofibrous membrane is based on PVB as the matrix material, adding Camellia oil (CO) and ZnO-TiO2 composite nanoparticles (ZT) as the active material. The antimicrobial property of the CO and the photocatalytic activity of the nanoparticles give the material good antimicrobial and ethylene degradation functions. Meanwhile, this nanofibrous membrane has good mechanical properties, suitable moisture permeability and good optical properties. The nanofibrous membrane are suitable for both climacteric and non- climacteric fruits. Its use as a cling film extends the shelf life of strawberries by 4 days and significantly slows the ripening of small tomatoes. Therefore, this nanofibrous membrane has great potential for application in the field of fruit preservation.

Effects of a nurse-led motor function rehabilitation training program for patients with ischemic stroke and family caregivers: study protocol for a randomized controlled trial.

BACKGROUND: Both individuals and society bear a considerable burden from ischemic stroke (IS), not only do patients continue suffering from motor dysfunction after discharge from hospital, but their caregivers also undertake the principal responsibility of assisting them in reintegrating into the family and society. To better improve the IS patients' limb function and daily life activities, their caregivers should also be involved in the training of the motor function rehabilitation during the period transitioning from hospital back home. This study mainly aims to investigate the effects of a nurse-led training for IS patients and their family caregivers on the improvement of the patients' physical function and the burden of caregivers. METHODS/DESIGN: A randomized controlled trial with blind assessment will be conducted in hospitals and during the follow-ups at home. Fifty-eight pairs of adults diagnosed with ischemic stroke and their primary caregivers will be included. Participants will be randomly given with (1) a nurse-led, home-based motor rehabilitation training participated by caregivers (intervention group) or (2) routine self-care (control group). Both groups will receive assessment and health guidance on the day of discharge, and the intervention group will receive an additional home-based training program and supervision. These two groups will be followed up every week after discharge. The primary results are drawn from the evaluation of physical function and caregiver-related burden, and the secondary results derived from statistics of the modified Barthel index, stroke-specific quality of life, and National Institutes of Health Stroke Scale. Differences between the two groups will be measured by two-way repeated measures ANOVA, considering the data at baseline and at 1-week and 4-week follow-up after training. DISCUSSION: Results may provide novel and valuable information on the effects of this culturally appropriate, caregiver-involved, and home-based rehabilitation training on the physical function of IS patients and caregiver-related burden. TRIAL REGISTRATION: Chinese Clinical Trial Registry (chictr.org.cn) ChiCTR2300078798. Registered on December 19, 2023.

Versatile Thermo-Sensitive liposomes with HSP inhibition and Anti-Inflammation for synergistic Chemo-Photothermal to inhibit breast cancer metastasis.

Photothermal therapy (PTT) is a prospective therapeutic method for breast cancer. However, excess inflammatory response induced by PTT may aggravate tumor metastasis. Meanwhile, the overexpressed heat shock proteins (HSPs) by cancer cells can protect them from hyperthermia during PTT. Therefore, to attenuate the PTT-induced inflammation and inhibit tumor metastasis, a folate receptor-targeted thermo-sensitive liposome (BI-FA-LP) co-loading Berberine (BBR) and Indocyanine green (ICG) was developed. BI-FA-LP utilized enhanced permeability and retention (EPR) effect and FA receptor-mediated endocytosis to selectively accumulate at tumor, reducing off-target toxicity during the treatment. After targeting to the tumor site, BBR and ICG were released from BI-FA-LP upon laser irradiation, and ICG showed good photothermal performance, while BBR inhibited HSP70 and HSP90 expression during PTT, exerting chemo-photothermal synergetic anti-tumor effect. Moreover, BBR could suppress the PTT induced inflammation, thus inhibiting tumor metastasis and ameliorating tissue injury. Thus, this versatile liposome provided a new strategy to enhance PTT and anti-inflammatory effects for breast cancer treatment.

Biomimetic Nanomodulators With Synergism of Photothermal Therapy and Vessel Normalization for Boosting Potent Anticancer Immunity.

Combination therapy using photothermal therapy (PTT) and immunotherapy is one of the most promising approaches for eliciting host immune responses to ablate tumors. However, its therapeutic efficacy is limited due to inefficient immune cell infiltration and cellular immune responses. In this study, a biomimetic immunostimulatory nanomodulator, Tm@PDA-GA (4T1 membrane@polydopamine-gambogic acid), with homologous targeting is developed. The 4T1 membrane (Tm) coating reduced immunogenicity and facilitated uptake of Tm@PDA-GA by tumor cells. Polydopamine (PDA) as a drug carrier can induce PTT under near-infrared ray (NIR) irradiation and immunogenic cell death (ICD) to activate dendritic cells (DCs). Moreover, Tm@PDA-GA on-demand released gambogic acid (GA) in an acidic tumor microenvironment, inhibiting the expression of heat shock proteins (HSPs) for synergetic chemo-photothermal anti-tumor activity and increasing the ICD of 4T1 cells. More importantly, GA can normalize the vessels via HIF-1α and VEGF inhibition to enhance immune infiltration and alleviate hypoxia stress. Thus, Tm@PDA-GA induced ICD, activated DCs, stimulated cytotoxic T cells, and suppressed Tregs. Moreover, Tm@PDA-GA is combined with anti-PD-L1 to further augment the tumor immune response and effectively suppress tumor growth and lung metastasis. In conclusion, biomaterial-mediated PTT combined with vessel normalization is a promising strategy for effective immunotherapy of triple-negative breast cancer (TNBC).

Risk factor patterns define social anxiety subtypes in adolescents with brain and clinical feature differences.

Social anxiety disorder (SAD) is one of the most common psychiatric disorders in adolescents. The heterogeneity of both symptoms and etiology is an essential source of difficulties in the treatment and prevention of SAD. The study aimed to identify subtypes of adolescent SAD based on etiology-related phenotype dimensions and examine symptom and brain associations of the subtypes. We used a deeply phenotyped sample (47 phenotype subscales from 13 measures) of adolescents with SAD (n = 196) and healthy controls (n = 109) to extract etiology-relevant risk factors, based on which we identified subtypes of SAD. We compared the subtypes on clinical characteristics and brain morphometrics and functional connectivity, and examined subtype-specific links between risk factors, brain aberrance, and clinical characteristics. We identified six etiology-relevant risk factors and two subtypes of adolescent SAD. One subtype showed mainly elevated negative emotionality trait and coping style and diminished positive emotionality trait and coping style, while the other additionally had significantly high environmental risk factors, more severe impairments in social functioning, and significant abnormalities in brain structure and function. There were subtype-specific links between the risk factor profiles, brain aberrance, and clinical characteristics. The finding suggests two etiology-based subtypes of adolescent SAD, providing novel insights to the diversity of pathological pathways and precise intervention strategies.

Identification of Penexanthone A as a Novel Chemosensitizer to Induce Ferroptosis by Targeting Nrf2 in Human Colorectal Cancer Cells.

Ferroptosis has emerged as a potential mechanism for enhancing the efficacy of chemotherapy in cancer treatment. By suppressing nuclear factor erythroid 2-related factor 2 (Nrf2), cancer cells may lose their ability to counteract the oxidative stress induced by chemotherapy, thereby becoming more susceptible to ferroptosis. In this study, we investigate the potential of penexanthone A (PXA), a xanthone dimer component derived from the endophytic fungus Diaporthe goulteri, obtained from mangrove plant Acanthus ilicifolius, to enhance the therapeutic effect of cisplatin (CDDP) on colorectal cancer (CRC) by inhibiting Nrf2. The present study reported that PXA significantly improved the ability of CDDP to inhibit the activity of and induce apoptosis in CRC cells. Moreover, PXA was found to increase the level of oxidative stress and DNA damage caused by CDDP. In addition, the overexpression of Nrf2 reversed the DNA damage and ferroptosis induced by the combination of PXA and CDDP. In vivo experiments using zebrafish xenograft models demonstrated that PXA enhanced the therapeutic effect of CDDP on CRC. These studies suggest that PXA enhanced the sensitivity of CRC to CDDP and induce ferroptosis by targeting Nrf2 inhibition, indicating that PXA might serve as a novel anticancer drug in combination chemotherapy.

Transforming Cancer Treatment with Nanotechnology: The Role of Berberine as a Star Natural Compound.

Berberine (BBR), recognized as an oncotherapeutic phytochemical, exhibits its anti-cancer properties via multiple molecular pathways. However, its clinical application is hindered by suboptimal tumor accumulation, rapid systemic elimination, and diminished bioactive concentration owing to extensive metabolic degradation. To circumvent these limitations, the strategic employment of nanocarriers and other drugs in combination with BBR is emerging as a focus to potentiate its anti-cancer efficacy. This review introduced the expansive spectrum of BBR's anti-cancer activities, BBR and other drugs co-loaded nanocarriers for anti-cancer treatments, and evaluated the synergistic augmentation of these amalgamated modalities. The aim is to provide an overview of BBR for cancer treatment based on nano-delivery. Berberine (BBR), recognized as an oncotherapeutic phytochemical, exhibits its anti-cancer properties via multiple molecular pathways. However, its clinical application is hindered by suboptimal tumor accumulation, rapid systemic elimination, and diminished bioactive concentration owing to extensive metabolic degradation. To circumvent these limitations, the strategic employment of nanocarriers and other drugs in combination with BBR is emerging as a focus to potentiate its anti-cancer efficacy. Nano-delivery systems increase drug concentration at the tumor site by improving pharmacological activity and tissue distribution, enhancing drug bioavailability. Organic nanocarriers have advantages for berberine delivery including biocompatibility, encapsulation, and controlled release of the drug. While the advantages of inorganic nanocarriers for berberine delivery mainly lie in their efficient loading ability of the drug and their slow release ability of the drug. This review introduced the expansive spectrum of BBR's anti-cancer activities, BBR and other drugs co-loaded nanocarriers for anti-cancer treatments, and evaluated the synergistic augmentation of these amalgamated modalities. The aim is to provide an overview of BBR for cancer treatment based on nano-delivery.

Analysis of Risk Factors for Secondary Endometrial Cancer-Related Death: A SEER-Based Study.

Purpose: The aim of this study was to analyze the survival of patients with endometrial cancer diagnosed after a prior cancer and identify risk factors of endometrial cancer death in this population. Methods: Totally 1371 women diagnosed with second primary endometrial cancer (SPEC) between 2004 and 2015 were identified using the SEER database. Clinicopathological characteristics were collected, and Fine and Gray regression model was employed to assess the impact of treatment for the first primary cancer (FPC) and SPEC on the mortality of endometrial cancer patients. After propensity score matching (PSM), patients diagnosed with single primary endometrial cancer and SPEC between 2004 and 2015 were included as the second cohort. Kaplan-Meier and Cox survival risk models were used to assess the influence of previous cancer history on survival. Results: Patients previously diagnosed as lung cancer exhibited the lowest overall survival (OS). A diagnostic interval of ≥3 years was significantly associated with higher mortality from SPEC compared with that <3 years. Surgical treatment for SPEC was linked to a reduced risk of endometrial cancer-specific mortality (ECSM) and non-ECSM. Conversely, radiotherapy and chemotherapy were associated with an increased risk of ECSM. The 1-, 3-, and 5-year OS rates of patients with SPEC were significantly lower than those with single primary endometrial cancer whether before or after PSM. Univariate and multivariate analyses further demonstrated that endometrial cancer, either as FPC or SPEC, was independently associated with an increased risk for endometrial cancer-specific survival (ECSS) and OS. Conclusion: Chemotherapy and radiotherapy for SPEC can elevate the risk of ECSM. Whether as FPC or SPEC, endometrial cancer is demonstrated to be a significant independent risk factor for ECSS and OS.

Photo-triggered AuAg@g-C3N4 composite nanoplatform for multimodal broad-spectrum antibacterial therapy.

Strategies based on nanomaterials for sterilization address the problem of antibiotic resistance faced by conventional antimicrobials, with the contribution of photocatalytic compounds being particularly prominent. Herein, to integrate multiple bactericidal techniques into a system for generating synergistic antibacterial effects, a novel photo-triggered AuAg@g-C3N4 composite nanoplatform was constructed by anchoring AuAg on the surface of a g-C3N4 layer. As the composite nanoplatform had a lower bandgap and superior visible light utilization efficiency, it could facilitate free electron transfer better and exhibit superior photocatalytic activity under light conditions. Moreover, the AuAg@g-C3N4 composite nanoplatform integrated the bactericidal modes of silver ion toxicity, physical disruption of bacterial cell membranes by the multilayer structure, and excellent photocatalytic activity, exhibiting extremely superior bactericidal effects against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis, with a bactericidal efficiency of up to 100%.

A rapid quantitative UPLC-MS/MS method for analysis of key regulatory oxysterols in biological samples for liver cancer.

An UPLC-APCI-MS/MS method was developed for the simultaneous determination of cholesterol, 7-dehydrocholesterol (7DHC) and eight oxysterols including 27-hydroxycholesterol (27OHC), 7α-hydroxycholesterol (7αOHC), 7ß-hydroxycholesterol (7ßOHC), 24S-hydroxycholesterol (24SOHC), 25-hydroxycholesterol (25OHC), 7α,24S-dihydroxycholesterol (7α,24SdiOHC), 7α,25-dihydroxycholesterol (7α,25diOHC), and 7α,27-dihydroxycholesterol (7α,27diOHC). It has been used for quantitative analysis of cholesterol, 7DHC and eight oxysterols in hepatocellular carcinoma (HCC) cells, plasma and tumor tissue samples. And the above compounds were extracted from the biological matrix (plasma and tissue) using liquid-liquid extraction with hexane/isopropanol after saponification to cleave the steroids from their esterified forms without further derivatization. Then cholesterol, 7DHC and oxysterols were separated on a reversed phase column (Agilent Zorbax Eclipse plus, C18) within 8 min using a gradient elution with 0.1 % formic acid in H2O and methanol and detected by an APCI triple quadrupole mass spectrometer. The lower limit of quantification (LLOQ) of the cholesterol, 7DHC and oxysterols ranged from 3.9 ng/mL to 31.25 ng/mL, and the recoveries ranged from 83.0 % to 113.9 %. Cholesterol, 7DHC and several oxysterols including 27OHC, 7αOHC and 7ßOHC were successfully quantified in HCC cells, plasma, tissues and urine of HCC mice. Results showed that 27OHC was at high levels in three kind of HCC cells and tumor tissues as well as plasma samples from both HepG2 and Huh7 bearing mice model，and the high levels of 27OHC in tumors were associated with HCC development. Moreover, the levels of cholesterol in HCC cells and tumor issues varied in different HCC cells and mice model. Oxysterols profiling in biological samples might provide complementary information in cancer diagnosis.

Activity-based protein profiling in drug/pesticide discovery: Recent advances in target identification of antibacterial compounds.

Given the escalating incidence of bacterial diseases and the challenge posed by pathogenic bacterial resistance, it is imperative to identify appropriate methodologies for conducting proteomic investigations on bacteria, and thereby promoting the target-based drug/pesticide discovery. Interestingly, a novel technology termed "activity-based protein profiling" (ABPP) has been developed to identify the target proteins of active molecules. However, few studies have summarized advancements in ABPP for identifying the target proteins in antibacterial-active compounds. In order to accelerate the discovery and development of new drug/agrochemical discovery, we provide a concise overview of ABPP and its recent applications in antibacterial agent discovery. Diversiform cases were cited to demonstrate the potential of ABPP for target identification though highlighting the design strategies and summarizing the reported target protein of antibacterial compounds. Overall, this review is an excellent reference for probe design towards antibacterial compounds, and offers a new perspective of ABPP in bactericide development.

Comparative study on pharmacokinetics of extract from Bufonis venenum and its liposomes.

Bufadienolides and indolealkylamines, the primary active components in Bufonis venenum, have rapid clearance from the body with a short half-life, leading to low bioavailability. Moreover, Bufadienolides and indolealkylamines are associated with serious adverse effects. In order to reduce the toxicities, minimize the adverse effects and simultaneously load lipophilic bufadienolides and hydrophilic indolealkylamines with satisfactory drug loading and encapsulation rate, we prepared Bufonis venenum extract-liposomes (BVE-LP). To compare the pharmacokinetic differences between Bufonis venenum extract (BVE) and its liposomes, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay was established to simultaneously detect the 12 chemical components in rat plasma. Results of pharmacokinetic study in SD rats showed that the highest exposure based on the area under the plasma concentration-time curve (AUC0-t) was obtained by 5-hydroxytryptamine with a mean value of 267.097 µg/L*h in BVE-LP group, which was 72.36 % higher as compared to that obtained in Bufonis venenum extract (BVE) group with a mean value of AUC0-t of 154.966 µg/L*h. The exposure (AUC0-t) of desacetylcinobufotalin, desacetylcinobufagin, arenobufagin and telocinobufagin in BVE-LP group was 111.89 %, 94.13 %, 134.08 %, and 92.94 % higher when compared to that in BVE group. With the employment of liposomes, there was an obvious decrease in the clearance of bufotenidine, desacetylcinobufotalin, gamabufotalin, arenobufagin, and telocinobufagin. The terminal half life (t1/2) of desacetylcinobufotalin, gamabufotalin, arenobufagin, and telocinobufagin in BVE-LP group was increased by 185.96 %, 292.64 %, 196.78 % and 131.29 % when compared to that in BVE group. All the results above indicated that a slower elimination rate and more exposure of some bufadienolides and indolealkylamines was obtained by BVE-LP when compared to BVE group, which verified BVE-LP could provide a therapeutic option for effective delivery of Bufonis venenum in clinical. DATA AVAILABILITY: The data will be shared on reasonable request to the corresponding author.

Fluorescence-enhanced supra-amphiphiles based on pillar[5]arene: construction, controllable self-assembly and application in cell imaging.

Fluorescence-enhanced supra-amphiphiles based on (WP5)2⊃ENDTn were constructed successfully. When n = 9, they can self-assemble into uniform micelles with an average diameter of about 90 nm and be further applied in cell imaging.

Evaluation of fragility fracture risk using deep learning based on ultrasound radio frequency signal.

BACKGROUND: It was essential to identify individuals at high risk of fragility fracture and prevented them due to the significant morbidity, mortality, and economic burden associated with fragility fracture. The quantitative ultrasound (QUS) showed promise in assessing bone structure characteristics and determining the risk of fragility fracture. AIMS: To evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragility fractures retrospectively in postmenopausal women, and compared it with the traditional parameter of QUS, speed of sound (SOS), and bone mineral density (BMD) acquired with dual X-ray absorptiometry (DXA). METHODS: Using QUS, RF signal and SOS were acquired for 246 postmenopausal women. An MResNet was utilized, based on the RF signal, to categorize individuals with an elevated risk of fragility fracture. DXA was employed to obtain BMD at the lumbar, hip, and femoral neck. The fracture history of all adult subjects was gathered. Analyzing the odds ratios (OR) and the area under the receiver operator characteristic curves (AUC) was done to evaluate the effectiveness of various methods in discriminating fragility fracture. RESULTS: Among the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was competent to discriminate any fragility fracture (OR = 2.64; AUC = 0.74), Vertebral fracture (OR = 3.02; AUC = 0.77), and non-vertebral fracture (OR = 2.01; AUC = 0.69). After being modified by clinical covariates, the efficiency of MResNet was further improved to OR = 3.31-4.08, AUC = 0.81-0.83 among all fracture groups, which significantly surpassed QUS-SOS (OR = 1.32-1.36; AUC = 0.60) and DXA-BMD (OR = 1.23-2.94; AUC = 0.63-0.76). CONCLUSIONS: This pilot cross-sectional study demonstrates that the MResNet model based on the ultrasonic RF signal shows promising performance in discriminating fragility fractures in postmenopausal women. When incorporating clinical covariates, the efficiency of the modified MResNet is further enhanced, surpassing the performance of QUS-SOS and DXA-BMD in terms of OR and AUC. These findings highlight the potential of the MResNet as a promising approach for fracture risk assessment. Future research should focus on larger and more diverse populations to validate these results and explore its clinical applications.

Machine learning-based prediction of supercapacitor capacitance for MgCo2O4 electrodes.

Electrode materials are essential in the electrochemical process of storing charge in supercapacitors and have a significant impact on the cost and capacitive performance of the final product. Hence, it is imperative to make precise predictions regarding the capacitance of electrode materials in order to further the development of supercapacitors. MgCo2O4, with a theoretical capacitance of up to 3122 F g-1, holds immense research value as an electrode material. The objective of this study is to predict the capacitance of MgCo2O4 with high accuracy. This will be achieved by extracting numerous data from published papers and using some parameters as input features. The Recursive Feature Elimination (RFE) method was employed, using Random Forest (RF), Extreme Gradient Boosting (XGBoost) and Regression Tree (RT) as selectors to identify the optimal feature subset. Then, combining them with these three regression models to construct nine machine learning (ML) models. After performance evaluation and outlier analysis, the XGB-RFE-XGB model achieved R-squared (R²), root mean squared error (RMSE), and mean absolute error (MAE) of 0.95, 111.83 F g-1 and 68.25 F g-1, respectively, demonstrating its stability and reliability. Therefore, the XGB-RFE-XGB model can be used as a reliable predictive tool in subsequent experimental designs.

Microplastic exposure inhibits nitrate uptake and assimilation in wheat plants.

Microplastic (MP) contamination in soil severely impairs plant growth. However, mechanisms underlying the effects of MPs on plant nutrient uptake remain largely unknown. In this study, we revealed that NO3- content was significantly decreased in shoots and roots of wheat plants exposed to high concentrations (50-100 mg L-1) of MPs (1 µm and 0.1 µm; type: polystyrene) in the hydroponic solution. Isotope labeling experiments demonstrated that MP exposure led to a significant inhibition of NO3- uptake in wheat roots. Further analysis indicated that the presence of MPs markedly inhibited root growth and caused oxidative damage to the roots. Additionally, superoxide dismutase and peroxidase activities in wheat roots decreased under all MP treatments, whereas catalase and ascorbate peroxidase activities significantly increased under the 100 mg L-1 MP treatment. The transcription levels of most nitrate transporters (NRTs) in roots were significantly downregulated by MP exposure. Furthermore, exposure to MPs distinctly suppressed the activity of nitrate reductase (NR) and nitrite reductase (NiR), as well as the expression levels of their coding genes in wheat shoots. These findings indicate that a decline in root uptake area and root vitality, as well as in the expression of NRTs, NR, and NiR genes caused by MP exposure may have adverse effects on NO3- uptake and assimilation, consequently impairing normal growth of plants.

Hepatic IL22RA1 deficiency promotes hepatic steatosis by modulating oxysterol in the liver.

BACKGROUND AND AIMS: An imbalance in lipid metabolism is the main cause of NAFLD. While the pathogenesis of lipid accumulation mediated by extrahepatic regulators has been extensively studied, the intrahepatic regulators modulating lipid homeostasis remain unclear. Previous studies have shown that systemic administration of IL-22 protects against NAFLD; however, the role of IL-22/IL22RA1 signaling in modulating hepatic lipid metabolism remains uncertain. APPROACH AND RESULTS: This study shows that hepatic IL22RA1 is vital in hepatic lipid regulation. IL22RA1 is downregulated in palmitic acid-treated mouse primary hepatocytes, as well as in the livers of NAFLD model mice and patients. Hepatocyte-specific Il22ra1 knockout mice display diet-induced hepatic steatosis, insulin resistance, impaired glucose tolerance, increased inflammation, and fibrosis compared with flox/flox mice. This is attributed to increased lipogenesis mediated by the accumulation of hepatic oxysterols, particularly 3 beta-hydroxy-5-cholestenoic acid (3ß HCA). Mechanistically, hepatic IL22RA1 deficiency facilitates 3ß HCA deposition through the activating transcription factor 3/oxysterol 7 alpha-hydroxylase axis. Notably, 3ß HCA facilitates lipogenesis in mouse primary hepatocytes and human liver organoids by activating liver X receptor-alpha signaling, but IL-22 treatment attenuates this effect. Additionally, restoring oxysterol 7 alpha-hydroxylase or silencing hepatic activating transcription factor 3 reduces both hepatic 3ß HCA and lipid contents in hepatocyte-specific Il22ra1 knockout mice. CONCLUSIONS: These findings indicate that IL22RA1 plays a crucial role in maintaining hepatic lipid homeostasis in an activating transcription factor 3/oxysterol 7 alpha-hydroxylase-dependent manner and establish a link between 3ß HCA and hepatic lipid homeostasis.

VISTA: A promising target for overcoming immune evasion in gynecologic cancers.

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but has shown limited efficacy in gynecologic cancers. VISTA (V-domain Ig suppressor of T-cell activation), a member of the B7 family, is emerging as another checkpoint that regulates the anti-tumor immune responses within the tumor microenvironment. This paper reviews the structure, expression, and mechanism of action of VISTA. Furthermore, it highlights recent advances in VISTA-blocking therapies and their potential in improving outcomes for patients with gynecologic cancers. By understanding the role of VISTA in mediating the immune evasion of gynecologic tumors, we can develop more effective combinatory treatment strategies that could overcome resistance to current ICB therapies.

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OBJECTIVES: To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. METHODS: A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. RESULTS: A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). CONCLUSIONS: The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.