Cross-domain pedestrian detection via feature alignment and image quality assessment.

Datasets collected under different sensors, viewpoints, or weather conditions cause different domains. Models trained on domain A applied to tasks of domain B result in low performance. To overcome the domain shift, we propose an unsupervised pedestrian detection method that utilizes CycleGAN to establish an intermediate domain and transform a large gap domain-shift problem into two feature alignment subtasks with small gaps. The intermediate domain trained with labels from domain A, after two rounds of feature alignment using adversarial learning, can facilitate effective detection in domain B. To further enhance the training quality of intermediate domain models, Image Quality Assessment (IQA) is incorporated. The experimental results evaluated on Citypersons, KITTI, and BDD100K show that MR of 24.58%, 33.66%, 28.27%, and 28.25% were achieved in four cross-domain scenarios. Compared with typical pedestrian detection models, our proposed method can better overcome the domain-shift problem and achieve competitive results.

Occurrence of black queen cell virus in wild bumble bee communities in China.

Wild bumble bees (Hymenoptera: Apidae) play a vital role in agro-ecosystems as important pollinators. However, they are threatened by virus pathogens that are widespread in honey bees. Previous studies have reported that viruses were able to be transmitted across bee genera and caused potential danger to wild bumble bees. China is a global biodiversity hotspot for bumble bees. However, the impact of viruses on the wild bumble bee communities remains elusive. Black queen cell virus (BQCV) is one of the most common honey bee viruses. Here, a total of 72 wild bumble bee samples from 17 geographic regions of China were tested for BQCV. Thirteen positive samples were identified and sequence comparison of partial capsid genes demonstrated a genetic identity of 99.69% to 100%. A phylogenetic tree analysis also showed a close relationship between 13 BQCV isolates and others from a variety of recorded hosts in China. Meanwhile, a distinct evolutionary branch of China isolates was formed when clustering isolates from worldwide bumble bee species. A correlation between BQCV and their geographic locations were observed (P < 0.05). This study not only provides the first evidence of widespread BQCV in wild bumble bee communities in China but also detects a distinct set of genetically identical or closely related BQCV variants that circulate and evolutionarily differ from other countries.

Nardilysin-regulated scission mechanism activates polo-like kinase 3 to suppress the development of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism.

Risk factors and genetic characteristics of the carriage of hypervirulent and carbapenem-resistant Acinetobacter baumannii among pregnant women.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) and its emerging evolutionary branch toward hypervirulence have been neglected in pregnancy. Methods: From September 2020 to August 2021, an active surveillance culture program encompassed 138 randomly selected pregnant women, with five subjected to sample collection at two different time points. The clinical characterization was explored through statistical analysis. Whole-genome sequencing, a Galleria mellonella infection model, and a global database were used to investigate the genetic characterization, pathogenicity, evolutionary history, and phylogenetic relationships of the isolates. Results: Of the 41 CRAB isolates obtained, they were divided into four ClustersRS and an orphan pattern. ClusterRS 1 (n = 31), with eight complex types in pregnancy, was also the dominant ClusterRS globally, followed by ClusterRS 13 (n = 5), identified as hypervirulent KL49 CRAB, exhibiting phylogeographical specificity to Guangdong. A maternal carriage CRAB rate of 26.09% (36/138) was revealed, with half of the isolates representing novel complex types, prominently including CT3071, as the first KL7 isolates identified in Shenzhen. Both KL49 and KL7 isolates were most commonly found in the same participant, suggesting potential intraspecific competition as a possible reason for CRAB infection without carriers during pregnancy. The independent risk factors for carriers were revealed for the first time, including advanced maternal age, gestational diabetes mellitus, and Group B Streptococcus infection. Conclusion: The significant carriage rate and enhanced virulence of CRAB during pregnancy emphasize the imperative for routine surveillance to forestall dissemination within this high-risk group, especially in Guangdong for ClusterRS 13 isolates.

Populus euphratica PeNADP-ME interacts with PePLDδ to mediate sodium and ROS homeostasis under salinity stress.

Populus euphratica phospholipase Dδ (PePLDδ) is transcriptionally regulated and mediates reactive oxygen species (ROS) and ion homeostasis under saline conditions. The purpose of this study is to explore the post-transcriptional regulation of PePLDδ in response to salt environment. P. euphratica PePLDδ was shown to interact with the NADP-dependent malic enzyme (NADP-ME) by screening the yeast two-hybrid libraries. The transcription level of PeNADP-ME increased upon salt exposure to NaCl (200 mM) in leaves and roots of P. euphratica. PeNADP-ME had a similar subcellular location with PePLDδ in the cytoplasm, and the interaction between PeNADP-ME and PePLDδ was further verified by GST pull-down and yeast two-hybrid. To clarify whether PeNADP-ME interacts with PePLDδ to enhance salt tolerance, PePLDδ and PeNADP-ME were overexpressed singly or doubly in Arabidopsis thaliana. Dual overexpression of PeNADP-ME and PePLDδ resulted in an even more pronounced improvement in salt tolerance compared with single transformants overexpressing PeNADP-ME or PePLDδ alone. Greater Na+ limitation and Na+ efflux in roots were observed in doubly overexpressed plants compared with singly overexpressed plants with PeNADP-ME or PePLDδ. Furthermore, NaCl stimulation of SOD, APX, and POD activity and transcription were more remarkable in the doubly overexpressed plants. It is noteworthy that the enzymic activity of NADP-ME and PLD, and total phosphatidic acid (PA) concentrations were significantly higher in the double-overexpressed plants than in the single transformants. We conclude that PeNADP-ME interacts with PePLDδ in Arabidopsis to promote PLD-derived PA signaling, conferring Na+ extrusion and ROS scavenging under salt stress.

Mechanisms used for cDNA synthesis and site-specific integration of RNA into DNA genomes by a reverse transcriptase-Cas1 fusion protein.

Reverse transcriptase-Cas1 (RT-Cas1) fusion proteins found in some CRISPR systems enable spacer acquisition from both RNA and DNA, but the mechanism of RNA spacer acquisition has remained unclear. Here, we found that Marinomonas mediterranea RT-Cas1/Cas2 adds short 3'-DNA (dN) tails to RNA protospacers, enabling their direct integration into CRISPR arrays as 3'-dN-RNAs or 3'-dN-RNA/cDNA duplexes at rates comparable to similarly configured DNAs. Reverse transcription of RNA protospacers is initiated at 3' proximal sites by multiple mechanisms, including recently described de novo initiation, protein priming with any dNTP, and use of short exogenous or synthesized DNA oligomer primers, enabling synthesis of near full-length cDNAs of diverse RNAs without fixed sequence requirements. The integration of 3'-dN-RNAs or single-stranded DNAs (ssDNAs) is favored over duplexes at higher protospacer concentrations, potentially relevant to spacer acquisition from abundant pathogen RNAs or ssDNA fragments generated by phage defense nucleases. Our findings reveal mechanisms for site-specifically integrating RNA into DNA genomes with potential biotechnological applications.

DB-1310, an ADC comprised of a novel anti-HER3 antibody conjugated to a DNA topoisomerase I inhibitor, is highly effective for the treatment of HER3-positive solid tumors.

BACKGROUND: HER3 (ErbB3), a member of the human epidermal growth factor receptor family, is frequently overexpressed in various cancers. Multiple HER3-targeting antibodies and antibody-drug conjugates (ADCs) were developed for the solid tumor treatment, however none of HER3-targeting agent has been approved for tumor therapy yet. We developed DB-1310, a HER3 ADC composed of a novel humanized anti-HER3 monoclonal antibody covalently linked to a proprietary DNA topoisomerase I inhibitor payload (P1021), and evaluate the efficacy and safety of DB-1310 in preclinical models. METHODS: The binding of DB-1310 to Her3 and other HER families were measured by ELISA and SPR. The competition of binding epitope for DB-1310 and patritumab was tested by FACS. The sensitivity of breast, lung, prostate and colon cancer cell lines to DB-1310 was evaluated by in vitro cell killing assay. In vivo growth inhibition study evaluated the sensitivity of DB-1310 to Her3 + breast, lung, colon and prostate cancer xenograft models. The safety profile was also measured in cynomolgus monkey. RESULTS: DB-1310 binds HER3 via a novel epitope with high affinity and internalization capacity. In vitro, DB-1310 exhibited cytotoxicity in numerous HER3 + breast, lung, prostate and colon cancer cell lines. In vivo studies in HER3 + HCC1569 breast cancer, NCI-H441 lung cancer and Colo205 colon cancer xenograft models showed DB-1310 to have dose-dependent tumoricidal activity. Tumor suppression was also observed in HER3 + non-small cell lung cancer (NSCLC) and prostate cancer patient-derived xenograft (PDX) models. Moreover, DB-1310 showed stronger tumor growth-inhibitory activity than patritumab deruxtecan (HER3-DXd), which is another HER3 ADC in clinical development at the same dose. The tumor-suppressive activity of DB-1310 synergized with that of EGFR tyrosine kinase inhibitor, osimertinib, and exerted efficacy also in osimertinib-resistant PDX model. The preclinical assessment of safety in cynomolgus monkeys further revealed DB-1310 to have a good safety profile with a highest non severely toxic dose (HNSTD) of 45 mg/kg. CONCLUSIONS: These finding demonstrated that DB-1310 exerted potent antitumor activities against HER3 + tumors in in vitro and in vivo models, and showed acceptable safety profiles in nonclinical species. Therefore, DB-1310 may be effective for the clinical treatment of HER3 + solid tumors.

Extracellular bioreduction is the main Cr(VI) detoxification strategy of Bacillus sp. HL1.

Bacterium with high Cr(VI) detoxification capability belonged to the genus Bacillus have been largely explored, yet their reduction strategies are still in debate. Cr(VI) removal performance and mechanism of Bacillus sp. HL1 isolated from tailings a site was comprehensively investigated in this study. Approximately 88.31% of 100 mg/L Cr(VI) was continuously removed within 72 h, while it could resist up to 300 mg/L Cr(VI). Metal ions Mn2+ and Cu2+ could effectively improve the Cr(VI) removal performance to 14.41% and 3.41% under the optimal conditions, respectively. Cr(VI) removal performances by subcellular extracts showed that nearly 45.28% of 100 mg/L extracellular Cr(VI) was efficaciously reduced to Cr(III), while only 14.27%, 6.40%, and 2.73% of the cell-free extract, resting cells, and cell debris were reduced, respectively. This suggested that extracellular bioreduction was the primary Cr(VI) detoxification strategy despite a small part of Cr(VI) reduction took place intracellularly. In particular, the reduction products of the intracellular and extracellular compounds significantly differed, with organo-Cr(III) complex outside the cell and crystalline Cr(III) precipitate inside. Such observation was also evidenced by the intracellular black precipitate observed in the TEM image. XRD, XPS, and EPR analysis showed different Cr(III) compositions of intracellular and extracellular products. This study deepens our insights into the different fates of microorganisms that reduce Cr(VI) intracellularly and extracellularly.

Effects of soil metal(loid)s pollution on microbial activities and environmental risks in an abandoned chemical smelting site.

Abandoned chemical smelting sites containing toxic substances can seriously threaten and pose a risk to the surrounding ecological environment. Soil samples were collected from different depths (0 to 13 m) and analyzed for metal(loid)s content and fractionation, as well as microbial activities. The potential ecological risk indices for the different soil depths (ordered from high to low) were: 1 m (D-1) > surface (S-0) > 5 m (D-5) > 13 m (D-13) > 9 m (D-9), ranging between 1840.65-13,089.62, and representing extremely high environmental risks, of which Cd (and probably not arsenic) contributed to the highest environmental risk. A modified combined pollution risk index (MCR) combining total content and mobile proportion of metal(loid)s, and relative toxicities, was used to evaluate the degree of contamination and potential environmental risks. For the near-surface samples (S-0 and D-1 layers), the MCR considered that As, Cd, Pb, Sb, and Zn achieved high and alarming degrees of contamination, whereas Fe, Mn, and Ti were negligible or low to moderate pollution degrees. Combined microcalorimetry and enzymatic activity measurements of contaminated soil samples were used to assess the microbial metabolic activity characteristics. Correlation analysis elucidated the relationship between metal(loid)s exchangeable fraction or content and microbial activity characteristics (p < 0.05). The microbial metabolic activity in the D-1 layer was low presumably due to heavy metal stress. Enzyme activity indicators and microcalorimetric growth rate (k) measurements were considered sensitive indicators to reflect the soil microbial activities in abandoned chemical smelting sites.

Double-balloon enteroscopy for the detection of GIST in a patient with neurofibromatosis type 1.

NF1 is an autosomal dominant hereditary disease, with a prevalence of at least 1 in 4000-5000 population. The diagnosis criteria of NF1 included typical manifestations such as café-au-lait spots, frecking in the axilla or inguinal region, multiple neurofibromas, Lisch nodeules, and distinctive osseous lesions. Genetic testing shows NF1 mutation. It is essential for tumor surveillance in NF1 patients because their life expectancy is about 54 years due to malignancy. A case of NF-1 patient receive laparoscopic small bowel resection and finally diagnosed as adenocarcinoma and ganglioneuroma. About 25% of NF1 patients had GISTs , most of them were asymptomatic and some may manifest with abdominal pain, bowel obstruction, or gastrointestinal bleeding. CT and MRI are commonly used imaging modalities for GIST in NF1, while they may be negative sometimes. As DBE a more practical and non-invasive method now, we consider it is a valuable method for screening and early detecting small intestine disease for NF1 patients.

Graphene-integrated mesh electronics with converged multifunctionality for tracking multimodal excitation-contraction dynamics in cardiac microtissues.

Cardiac microtissues provide a promising platform for disease modeling and developmental studies, which require the close monitoring of the multimodal excitation-contraction dynamics. However, no existing assessing tool can track these multimodal dynamics across the live tissue. We develop a tissue-like mesh bioelectronic system to track these multimodal dynamics. The mesh system has tissue-level softness and cell-level dimensions to enable stable embedment in the tissue. It is integrated with an array of graphene sensors, which uniquely converges both bioelectrical and biomechanical sensing functionalities in one device. The system achieves stable tracking of the excitation-contraction dynamics across the tissue and throughout the developmental process, offering comprehensive assessments for tissue maturation, drug effects, and disease modeling. It holds the promise to provide more accurate quantification of the functional, developmental, and pathophysiological states in cardiac tissues, creating an instrumental tool for improving tissue engineering and studies.

Shikonin attenuates cerebral ischemia/reperfusion injury via inhibiting NOD2/RIP2/NF-κB-mediated microglia polarization and neuroinflammation.

OBJECTIVES: Microglia-mediated neuroinflammation plays a crucial role in the pathophysiological process of multiple neurological disorders such as ischemic stroke, which still lacks effective therapeutic agents. Shikonin possesses anti-inflammatory and neuroprotective properties. However, its underlying mechanism remains elusive. This study aimed to investigate whether Shikonin confers protection against cerebral ischemia/reperfusion (I/R) injury by modulating microglial polarization and elucidate the associated mechanisms. METHODS: This study employed an oxygen-glucose deprivation and reoxygenation (OGD/R) BV2 microglial cellular model and a middle cerebral artery occlusion/reperfusion (MCAO/R) animal model to investigate the protection and underlying mechanism of Shikonin against ischemic stroke. RESULTS: The results demonstrated that Shikonin treatment significantly reduced brain infarction volume and improved neurological function in MCAO/R rats. Simultaneously, Shikonin treatment significantly reduced microglial proinflammatory phenotype and levels of proinflammatory markers (inducible-NO synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and IL-6), increased microglial anti-inflammatory phenotype and levels of anti-inflammatory markers (Arginase-1 (Arg1), transforming growth factor-beta (TGF-ß), and IL-10), reversed the expression of Nucleotide-binding oligomerization domain 2 (NOD2) and phosphorylation receptor interacting protein 2 (p-RIP2), and suppressed nuclear factor kappa-B (NF-κB) signaling activation in the ischemic penumbra regions. These effects of Shikonin were further corroborated in OGD/R-treated BV2 cells. Furthermore, overexpression of NOD2 markedly attenuated the neuroprotective effects of Shikonin treatment in MCAO/R rats. NOD2 overexpression also attenuated the regulatory effects of Shikonin on neuroinflammation, microglial polarization, and NF-κB signaling activation. CONCLUSION: This study illustrates that Shikonin mitigates inflammation mediated by microglial proinflammatory polarization by inhibiting the NOD2/RIP2/NF-κB signaling pathway, thereby exerting a protective role. The findings uncover a potential molecular mechanism for Shikonin in treating ischemic stroke.

Peripheral nerve blocks of wrist and finger flexors can increase hand opening in chronic hemiparetic stroke.

Introduction: Hand opening is reduced by abnormal wrist and finger flexor activity in many individuals with stroke. This flexor activity also limits hand opening produced by functional electrical stimulation (FES) of finger and wrist extensor muscles. Recent advances in electrical nerve block technologies have the potential to mitigate this abnormal flexor behavior, but the actual impact of nerve block on hand opening in stroke has not yet been investigated. Methods: In this study, we applied the local anesthetic ropivacaine to the median and ulnar nerve to induce a complete motor block in 9 individuals with stroke and observed the impact of this block on hand opening as measured by hand pentagonal area. Volitional hand opening and FES-driven hand opening were measured, both while the arm was fully supported on a haptic table (Unloaded) and while lifting against gravity (Loaded). Linear mixed effect regression (LMER) modeling was used to determine the effect of Block. Results: The ropivacaine block allowed increased hand opening, both volitional and FES-driven, and for both unloaded and loaded conditions. Notably, only the FES-driven and Loaded condition's improvement in hand opening with the block was statistically significant. Hand opening in the FES and Loaded condition improved following nerve block by nearly 20%. Conclusion: Our results suggest that many individuals with stroke would see improved hand-opening with wrist and finger flexor activity curtailed by nerve block, especially when FES is used to drive the typically paretic finger and wrist extensor muscles. Such a nerve block (potentially produced by aforementioned emerging electrical nerve block technologies) could thus significantly address prior observed shortcomings of FES interventions for individuals with stroke.

Lable-free aptamer portable colorimetric smartphone for gliadin detection in food.

For individuals with celiac disease (CD), the current clinical therapy option available is a lifelong gluten-free diet. Therefore, it is essential to swiftly and efficiently detect gluten in foods. A colorimetric sensor has been developed, which operates by regulating the aggregation and dispersion state of AuNPs induced by high concentration NaCl through the specific binding of gliadin and aptamer, thereby achieving rapid detection of gliadin in flour. It is found that the sensor exhibits good linearity in the concentration range of 0.67-10 µM and the LOD (3σ/S) is 12 nM. And it can accurately distinguish various types of free-gliadin samples, with a spiked recovery rate of 85%-122.3%. To make the detection process more convenient, the colorimetric results of the biosensor were translated into RGB color-gamut parameters by a smartphone color-picking program for further analysis. Gliadin can still be accurately quantified with the established smartphone platform, and a correlation coefficient of 0.988 was found. The proposed portable smartphone aptamer colorimetric sensing device has achieved satisfactory results in the rapid detection of gliadin in food.

Reference Genes Selection and Validation for Cinnamomum burmanni by Real-Time Quantitative Polymerase Chain Reaction.

In recent years, the field of biology has witnessed a surge of interest in genomics research due to the advancements in biotechnology. Gene expression pattern analysis plays a crucial role in this research, as it enables us to understand the regulatory mechanism of gene expression and the associated biological processes. Real-time quantitative polymerase chain reaction (q-PCR) is an efficient method to analyze the gene expression patterns, for which accuracy relies on the standardized analysis of reference genes. However, numerous studies have shown that no reference gene is universal in all conditions, so screening a suitable reference gene under certain conditions is of great importance. Cinnamomum burmannii (C. burmannii) is rich in volatile components and has high medicinal and economic value. However, knowledge of the screening of reference genes for the gene expression analysis of C. burmannii is insufficient. Aiming at this problem, we evaluated and screened the reference genes in C. burmannii under different experimental conditions, including different abiotic stresses (Cold-treated, PEG-treated and Nacl-treated), different tissues, leaves at different developmental stages and different chemical types. In this study, different algorithms (∆Ct, geNorm, NormFinder and BestKeeper) were used to evaluate the stability of the candidate reference genes, and RefFinder further merged the output data to screen out the optimum reference gene under various experimental conditions in C. burmannii. The results showed that the optimal reference gene number for gene standardization was 2 under different experimental conditions. RPL27|RPS15 was the most suitable combination under the Nacl-treated and PEG-treated samples. RPL27|APT was the optimum combination under the Cold-treated samples. The optimal combinations of other samples were EF1α|ACT7 for different tissues, eIF-5A|Gllα for different borneol clones in C. burmannii, RPS15|ACT7 for leaves at different developmental stages and RPS15|TATA for all samples. Additionally, two terpenoid synthesis-related genes (CbWRKY4 and CbDXS2) were standardized to verify the feasibility of the selected reference genes under different experimental conditions. This study will be helpful for the subsequent molecular genetic mechanism study of C. burmannii.

Ginsenoside Rd enhances blood-brain barrier integrity after cerebral ischemia/reperfusion by alleviating endothelial cells ferroptosis via activation of NRG1/ErbB4-mediated PI3K/Akt/mTOR signaling pathway.

The incidence of ischemic stroke is increasing year by year and showing a younger trend. Impaired blood-brain barrier (BBB) is one of the pathological manifestations caused by cerebral ischemia, leading to poor prognosis of patients. Accumulating evidence indicates that ferroptosis is involved in cerebral ischemia/reperfusion injury (CIRI). We have previously demonstrated that Ginsenoside Rd (G-Rd) protects against CIRI-induced neuronal injury. However, whether G-Rd can attenuate CIRI-induced disruption of the BBB remains unclear. In this study, we found that G-Rd could upregulate the levels of ZO-1, occludin, and claudin-5 in ipsilateral cerebral microvessels and bEnd.3 cells, reduce endothelial cells (ECs) loss and Evans blue (EB) leakage, and ultimately improve BBB integrity after CIRI. Interestingly, the expressions of ACSL4 and COX2 were upregulated, the expressions of GPX4 and xCT were downregulated, the levels of GSH was decreased, and the levels of MDA and Fe2+ were increased in ischemic tissues and bEnd.3 cells after CIRI, suggesting that ECs ferroptosis occurred after CIRI. However, G-Rd can alleviate CIRI-induced BBB disruption by inhibiting ECs ferroptosis. Mechanistically, G-Rd prevented tight junction loss and BBB leakage by upregulating NRG1, activating its tyrosine kinase ErbB4 receptor, and then activating downstream PI3K/Akt/mTOR signaling, thereby inhibiting CIRI-induced ferroptosis in ECs. Taken together, these data provides data support for G-Rd as a promising therapeutic drug for cerebral ischemia.

BRCA1-mediated dual regulation of ferroptosis exposes a vulnerability to GPX4 and PARP co-inhibition in BRCA1-deficient cancers.

Resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) limits the therapeutic efficacy of PARP inhibition in treating breast cancer susceptibility gene 1 (BRCA1)-deficient cancers. Here we reveal that BRCA1 has a dual role in regulating ferroptosis. BRCA1 promotes the transcription of voltage-dependent anion channel 3 (VDAC3) and glutathione peroxidase 4 (GPX4); consequently, BRCA1 deficiency promotes cellular resistance to erastin-induced ferroptosis but sensitizes cancer cells to ferroptosis induced by GPX4 inhibitors (GPX4i). In addition, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and defective GPX4 induction unleash potent ferroptosis in BRCA1-deficient cancer cells upon PARPi and GPX4i co-treatment. Finally, we show that xenograft tumors derived from BRCA1-mutant breast cancer patients with PARPi resistance exhibit decreased GPX4 expression and high sensitivity to PARP and GPX4 co-inhibition. Our results show that BRCA1 deficiency induces a ferroptosis vulnerability to PARP and GPX4 co-inhibition and inform a therapeutic strategy for overcoming PARPi resistance in BRCA1-deficient cancers.

Bioindicator responses to extreme conditions: Insights into pH and bioavailable metals under acidic metal environments.

Acid mine drainage (AMD) caused environmental risks from heavy metal pollution, requiring treatment methods such as chemical precipitation and biological treatment. Monitoring and adapting treatment processes was crucial for success, but cost-effective pollution monitoring methods were lacking. Using bioindicators measured through 16S rRNA was a promising method to assess environmental pollution. This study evaluated the effects of AMD on ecological health using the ecological risk index (RI) and the Risk Assessment Code (RAC) indices. Additionally, we also examined how acidic metal stress affected the diversity of bacteria and fungi, as well as their networks. Bioindicators were identified using linear discriminant analysis effect size (LEfSe), Partial least squares regression (PLS-R), and Spearman analyses. The study found that Cd, Cu, Pb, and As pose potential ecological risks in that order. Fungal diversity decreased by 44.88% in AMD-affected areas, more than the 33.61% decrease in bacterial diversity. Microbial diversity was positively correlated with pH (r = 0.88, p = 0.04) and negatively correlated with bioavailable metal concentrations (r = -0.59, p = 0.05). Similarly, microbial diversity was negatively correlated with bioavailable metal concentrations (bio_Cu, bio_Pb, bio_Cd) (r = 0.79, p = 0.03). Acidiferrobacter and Thermoplasmataceae were prevalent in acidic metal environments, while Puia and Chitinophagaceae were identified as biomarker species in the control area (LDA>4). Acidiferrobacter and Thermoplasmataceae were found to be pH-tolerant bioindicators with high reliability (r = 1, P < 0.05, BW > 0.1) through PLS-R and Spearman analysis. Conversely, Puia and Chitinophagaceae were pH-sensitive bioindicators, while Teratosphaeriaceae was a potential bioindicator for Cu-Zn-Cd metal pollution. This study identified bioindicator species for acid and metal pollution in AMD habitats. This study outlined the focus of biological monitoring in AMD acidic stress environments, including extreme pH, heavy metal pollutants, and indicator species. It also provided essential information for heavy metal bioremediation, such as the role of omics and the effects of organic matter on metal bioavailability.

How is intergenerational emotional cohesion linked to depression among older internal migrants in China: the mediating roles of loneliness and perceived stress.

BACKGROUND: Late-life internal migration is frequently associated with a higher risk of depression in older parents. This research delves into the impact of intergenerational emotional cohesion (IEC) on depression in older internal migrants and the underlying mechanisms within the contemporary Chinese context. METHODS: Obtained from a cross-sectional survey in Nanjing, China, the research involved 654 older internal migrants (66.97% female; mean age = 66.05 years; SD = 4.67). Variables were assessed using the Intergenerational Solidarity Inventory, 3-item R-UCLA Loneliness Scale, Perceived Stress Scale, and 9-item Patient Health Questionnaire (PHQ-9). For mediation exploration, a serial mediation model was utilized, and the Bootstrap method was employed to test the signifcance of these mediation effects. RESULTS: IEC demonstrates a negative correlation with depression. Through IEC, three significant mediation pathways were identified that directly affect depression: (1) loneliness (ß=-0.06; Ratio=17.14%), (2) perceived stress (ß=-0.09; Ratio=25.71%), and (3) loneliness and perceived stress (ß=-0.03; Ratio=8.57%). CONCLUSIONS: IEC can impact the depression of older internal migrants by mitigating negative psychological emotions during the migration process. This finding provides valuable theoretical insights for the prevention of mental health problems among this demographic.

Isolation and Characterization of Yunnan Variants of the Pseudorabies Virus and Their Pathogenicity in Rats.

Porcine pseudorabies has long existed in China and is a serious threat to the Chinese farming industry. To understand the prevalence and genetic variation of the porcine pseudorabies virus (PRV) and its pathogenicity in Yunnan Province, China, we collected 560 serum samples across seven Yunnan Province regions from 2020 to 2021 and detected anti-gE antibodies in these samples. Sixty-one clinical tissue samples were also collected from pigs with suspected PRV that were vaccinated with Bartha-K61. PRV-gE antibodies were found in 29.6% (166/560) of the serum samples. The PRV positivity rate in clinical tissue samples was 13.1% (8/61). Two isolates, PRV-KM and PRV-QJ, were obtained. The identity of the gB, gD, and gE genes between these isolates and the Chinese mutants exceeded 99.5%. These isolates and the classical Fa strain were used to infect 4-week-old rats intranasally to assess their pathogenicity. All infected rats showed the typical clinical and pathological features of PRV two days post-infection. The viral loads in the organs differed significantly among the infected groups. Viruses were detected in the saliva and feces at 12 h. Significant dynamic changes in total white blood cell counts (WBC), lymphocyte counts (Lym), and neutrophil counts (Gran) occurred in the blood of the infected groups at 24 and 48 h. These results show that mutant PRV strains are prevalent in Bartha-K61-vaccinated pigs in Yunnan Province, China. Moreover, rats shed PRV in their saliva and feces during early infection, indicating the need for rodent control in combatting PRV infections in Yunnan Province, China.