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Abstract Background In the central nervous system, type 2 vesicular monoamine transporters (VMAT2) are responsible for the reuptake of monoamines from synaptic junction back to pre-synaptic terminal vesicles. These transporters are functionally crucial as they reflect the integrity of monoamine neurons. D6-[18F]FP-(+)-DTBZ, a novel deuterated VMAT2 radioligand, has shown promise as a potential PET tracer for the diagnosis of Parkinson’s disease (PD). This study evaluates the biodistribution and dosimetry of D6-[18F]FP-(+)-DTBZ and includes a head-to-head comparison with its non-deuterated version, [18F]FP-(+)-DTBZ (AV-133), in healthy individuals and PD patients. Results The automated synthesis of D6-[18F]FP-(+)-DTBZ using the SPE method was accomplished in 35 min, yielding a high radiochemical purity (> 99%) and high radiochemical yields (35 ± 5%). The biodistribution and dosimetry study indicated an effective dose of 37.1 ± 7.2 μSv/MBq, with the liver receiving the highest radiation dose (289.6 ± 42.1 μGy/MBq), followed by pancreas (185.2 ± 29.1 μGy/MBq). Brain imaging with D6-[18F]FP-(+)-DTBZ exhibited a significantly increased uptake in VMAT2-rich regions, particularly the striatum. In a head-to-head comparison between [18F]FP-(+)-DTBZ and D6-[18F]FP-(+)-DTBZ, the latter exhibited approximately 15% higher SUVR in the caudate, putamen, and nucleus accumbens. Preliminary studies in PD patients showed a substantial reduction in VMAT2 uptake in the striatum, with the most pronounced decrease observed in the putamen (a 53% decline). Conclusions D6-[18F]FP-(+)-DTBZ is a safe and improved VMAT2-specific imaging agent, which may be suitable for diagnosing PD by evaluating changes in VMAT2 binding of monoamine neurons in the brain. Trial registration Chinese Clinical Trial Registry, ChiCTR2200057218, Registered 16 August 2021, https://www.chictr.org.cn/bin/project/edit?pid=142725 .

Background: This systematic scoping review aims to synthesize research findings on the clinical manifestations in patients with non-alcoholic fatty liver disease (NAFLD) and sarcopenia, focusing on studies published between December 2013 and December 2023. Summary: We conducted a comprehensive systematic scoping review of five databases and identified 312 articles, with 9 studies included in the final review. Most were cross-sectional investigations, and 70% were from Asian cohorts. A comparative analysis revealed that patients with both NAFLD and sarcopenia tended to be older, had a higher body mass index, and a higher prevalence among females. These findings emphasize the role of unhealthy lifestyles and obesity. Common comorbidities included metabolic syndrome, hypertension, and diabetes. However, the lack of standardized diagnostic criteria poses a significant challenge in accurately identifying this patient subgroup. Key Messages: This review highlights distinct clinical characteristics in NAFLD patients with sarcopenia, such as older age, higher body mass index, and a higher prevalence in females. Comorbidities also play a significant role. However, the lack of comprehensive studies limits early detection and intervention. Future research should address these gaps by developing standardized diagnostic criteria and effective management strategies for this patient group.

Abstract Purpose Currently, deep learning methods for the classification of benign and malignant lung nodules encounter challenges encompassing intricate and unstable algorithmic models, limited data adaptability, and an abundance of model parameters.To tackle these concerns, this investigation introduces a novel approach: the 3D Global Coordinated Attention Wide Inverted ResNet Network (GC-WIR). This network aims to achieve precise classification of benign and malignant pulmonary nodules, leveraging its merits of heightened efficiency, parsimonious parameterization, and robust stability. Methods Within this framework, a 3D Global Coordinate Attention Mechanism (3D GCA) is designed to compute the features of the input images by converting 3D channel information and multi-dimensional positional cues. By encompassing both global channel details and spatial positional cues, this approach maintains a judicious balance between flexibility and computational efficiency. Furthermore, the GC-WIR architecture incorporates a 3D Wide Inverted Residual Network (3D WIRN), which augments feature computation by expanding input channels. This augmentation mitigates information loss during feature extraction, expedites model convergence, and concurrently enhances performance. The utilization of the inverted residual structure imbues the model with heightened stability. Results Empirical validation of the GC-WIR method is performed on the LUNA 16 dataset, yielding predictions that surpass those generated by previous models. This novel approach achieves an impressive accuracy rate of 94.32%, coupled with a specificity of 93.69%. Notably, the model’s parameter count remains modest at 5.76M, affording optimal classification accuracy. Conclusion Furthermore, experimental results unequivocally demonstrate that, even under stringent computational constraints, GC-WIR outperforms alternative deep learning methodologies, establishing a new benchmark in performance.

Abstract Brown planthopper (BPH) is the most destructive insect pest of rice. Drought is the most detrimental environmental stress. BPH infestation causes adaxial leaf-rolling and bulliform cells (BCs) shrinkage similar to drought. The BC-related abaxially curled leaf1 (ACL1) gene negatively regulates BPH resistance and drought tolerance, with decreased cuticular wax in the gain-of-function mutant ACL1-D. ACL1 shows an epidermis-specific expression. The TurboID system and multiple biochemical assays reveal that ACL1 interacts with the epidermal-characteristic rice outermost cell-specific (ROC) proteins. ROC4 and ROC5 positively regulate BPH resistance and drought tolerance through modulating cuticular wax and BCs, respectively. Overexpression of ROC4 and ROC5 both rescue ACL1-D mutant in various related phenotypes. ACL1 competes with ROC4/ROC5 in homo-dimer and hetero-dimer formation, and interacts with the repressive TOPLESS-related proteins. Altogether, we illustrate that ACL1–ROC4/5 complexes synergistically mediate drought tolerance and BPH resistance through regulating cuticular wax content and BC development in rice, a mechanism that might facilitate BPH-resistant breeding.

Abstract Pneumolysin (Ply) of Streptococcus pneumoniae (pneumococcus) at relatively high and low levels facilitates pneumococcal invasion into the lung and brain, respectively; however, the regulatory mechanisms of Ply expression are poorly understood. Here, we find that a small RNA plyT, processed from the 3’UTR of the ply operon, is expressed higher in anaerobically- than in statically-cultured pneumococcus D39. Using bioinformatic, biochemical and genetic approaches, we reveal that PlyT inhibits Ply synthesis and hemolytic activities by pairing with an RBS-embedded intergenic region of the ply operon. The RNA-binding protein SPD_1558 facilitates the pairing. Importantly, PlyT inhibition of Ply synthesis is stronger in anaerobic culture and leads to lower Ply abundance. Deletion of plyT decreases the number of pneumococci in the infected mouse brain and reduces the virulence, demonstrating that PlyT-regulated lower Ply in oxygen-void microenvironments, such as the blood, is important for pneumococcus to cross the blood-brain barrier and invade the brain. PlyT-mediated repression of Ply synthesis at anoxic niches is also verified in pneumococcal serotype 4 and 14 strains; moreover, the ply operon with a 3’UTR-embedded plyT, and the pairing sequences of IGR and plyT are highly conserved among pneumococcal strains, implying PlyT-regulated Ply synthesis might be widely employed by pneumococcus.

Abstract Manipulating grain size demonstrates great potential for yield promotion in cereals since it is tightly associated with grain weight. Several pathways modulating grain size have been elaborated in rice, but possible crosstalk between the ingredients is rarely studied. OsmiR396 negatively regulates grain size through targeting OsGRF4 (GS2) and OsGRF8, and proves to be multi-functioning. Here we showed that expression of GS3 gene, a Gγ-protein encoding gene, that negatively regulates grain size, was greatly down-regulated in the young embryos of MIM396, GRF8OE and GS2OE plants, indicating possible regulation of GS3 gene by OsmiR396/GRF module. Meanwhile, multiple biochemical assays proved possible transcriptional regulation of OsGRF4 and OsGRF8 proteins on GS3 gene. Further genetic relation analysis revealed tight genetic association between not only OsmiR396 and GS3 gene, but also GS2 and GS3 gene. Moreover, we revealed possible regulation of GS2 on four other grain size-regulating G protein encoding genes. Thus, the OsmiR396 pathway and the G protein pathway cross talks to regulate grain size. Therefore, we established a bridge linking the miRNA-transcription factors pathway and the G-protein signaling pathway that regulates grain size in rice.

Abstract Traditional vehicular edge computing research usually ignores the mobility of vehicles, the dynamic variability of the vehicular edge environment, the large amount of real‐time data required for vehicular edge computing, the limited resources of edge servers, and collaboration issues. In response to these challenges, this article proposes a vehicular edge computing optimization scheme based on the Lyapunov function and Deep Reinforcement Learning. In this solution, this article uses Digital Twin technology (DT) to simulate the vehicular edge environment. The edge server DT is used to simulate the vehicular edge environment under the edge server, and the base station DT is used to simulate the entire vehicular edge system environment. Based on the real‐time data obtained from DT simulation, this paper defines the Lyapunov function to simplify the migration cost of vehicle tasks between servers into a multi‐objective dynamic optimization problem. It solves the problem by applying the Twin Delayed Deep Deterministic Policy Gradient (TD3) algorithm. Experimental results show that compared with other algorithms, this scheme can effectively optimize the allocation and collaboration of vehicular edge computing resources and reduce the delay and energy consumption caused by vehicle task processing.

Abstract Plants possess the ability to induce programmed cell death (PCD) in response to abiotic and biotic stresses; nevertheless, the evidence on PCD initiation during pear scald development and the involvement of the scald trigger 6-methyl-5-hepten-2-one (MHO) in this process is rudimentary. Pyrus bretschneideri Rehd. cv. ‘Dangshansuli’ pear was used to validate such hypothesis. The results showed that superficial scald occurred after 120-d chilling exposure, which accompanied by typical PCD-associated morphological alterations, such as plasmolysis, cell shrinkage, cytosolic and nuclear condensation, vacuolar collapse, tonoplast disruption, subcellular organelle swelling, and DNA fragmentation. These symptoms were aggravated after MHO fumigation but alleviated by diphenylamine (DPA) dipping. Through transcriptome assay, 24 out of 146 PCD-related genes, which were transcribed during cold storage, were identified as the key candidate members responsible for these cellular biological alternations upon scald development. Among these, PbrCNGC1, PbrGnai1, PbrACD6, and PbrSOBIR1 were implicated in the MHO signaling pathway. Additionally, PbrWRKY2, 34 and 39 could bind to the W-box element in the promoter of PbrGnai1 or PbrSOBIR1 and activate their transcription, as confirmed by dual-luciferase, yeast one-hybrid, and transient overexpression assays. Hence, our study confirms the PCD initiation during scald development and explores the critical role of MHO in this process.

Abstract Despite advancements in antiretroviral therapy (ART) suppressing HIV-1 replication, existing antiviral drugs pose limitations, including lifelong medication, frequent administration, side effects and viral resistance, necessitating novel HIV-1 treatment approaches. CD4, pivotal for HIV-1 entry, poses challenges for drug development due to neutralization and cytotoxicity concerns. Nevertheless, Ibalizumab, the sole approved CD4-specific antibody for HIV-1 treatment, reignites interest in exploring alternative anti-HIV targets, emphasizing CD4’s potential value for effective drug development. Here, we explore anti-CD4 nanobodies, particularly Nb457 from a CD4-immunized alpaca. Nb457 displays high potency and broad-spectrum activity against HIV-1, surpassing Ibalizumab’s efficacy. Strikingly, engineered trimeric Nb457 nanobodies achieve complete inhibition against live HIV-1, outperforming Ibalizumab and parental Nb457. Structural analysis unveils Nb457-induced CD4 conformational changes impeding viral entry. Notably, Nb457 demonstrates therapeutic efficacy in humanized female mouse models. Our findings highlight anti-CD4 nanobodies as promising HIV-1 therapeutics, with potential implications for advancing clinical treatment against this global health challenge.

Abstract Bladder cancer remains a significant health challenge due to its high recurrence and progression rates. This study aims to evaluate the role of POLR3G in the development and progression of bladder cancer and the potential of POLR3G to serve as a novel therapeutic target. We constructed a bladder cancer model in Wistar rats by administering N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), which successfully induced a transition from normal mucosa to hyperplasia and ultimately to urothelial carcinoma. We observed a progressive upregulation of POLR3G expression during the bladder cancer development and progression. To investigate the functional role of POLR3G, we performed functional experiments in bladder cancer cell lines. The results demonstrated that knocking down POLR3G significantly inhibited cell proliferation, migration, and invasion. We further conducted RNA sequencing on POLR3G-knockdown bladder cancer cells, and Metascape was employed to perform the functional enrichment analysis of the differentially expressed genes (DEGs). Enrichment analysis revealed the enrichment of DEGs in the RNA polymerase and apoptotic cleavage of cellular proteins pathways, as well as their involvement in the Wnt and MAPK signaling pathways. The downregulation of Wnt pathway-related proteins such as Wnt5a/b, DVL2, LRP-6, and phosphorylated LRP-6 upon POLR3G knockdown was further confirmed by Western blotting, indicating that POLR3G might influence bladder cancer behavior through the Wnt signaling pathway. Our findings suggest that POLR3G plays a crucial role in bladder cancer progression and could serve as a potential therapeutic target. Future studies should focus on the detailed mechanisms by which POLR3G regulates these signaling pathways and its potential as a biomarker for early detection and prognosis of bladder cancer.

Abstract Background Numerous meta-analyses and clinical studies have shown that subtypes of immune cells are associated with the development of skin cancer, but it is not clear whether this association is causal or biased. Mendelian randomization (MR) analysis reduces the effect of confounding factors and improves the accuracy of the results when compared to traditional studies. Thus, in order to examine the causal relationship between various immune cell and skin cancer, this study employs two-sample MR. Methods This study assesses the causal association between 731 immune cell characteristics and skin cancer using a two-sample Mendel randomization (MR) methodology. Multiple MR methods were used to bias and to derive reliable estimates of causality between instrumental variables and outcomes. Comprehensive sensitivity analyses were used to validate the stability, heterogeneity and horizontal multiplicity of the results. Results We discovered that potential causal relationships between different types of immune cells and skin cancer disease. Specifically, one type of immune cell as potentially causal to malignant melanoma of skin (MM), eight different types of immune cells as potentially causal to basal cell carcinoma (BCC), four different types of immune cells as potentially causal to actinic keratosis (AK), and no different types of immune cells were found to have a potential causal association with squamous cell carcinoma(SCC), with stability in all of the results. Conclusion This study demonstrates the close connection between immune cells and skin cancer disease by genetic means, which enriches the current knowledge about the role of immune cells in skin cancer and also contributes to the design of therapeutic strategies from an immunological perspective.

Abstract Ischemic stroke is a complex, high-mortality disease with multifactorial etiology and pathogenesis. Currently, drug therapy is mainly used treat ischemic stroke in clinic, but there are still some limitations, such as limited blood-brain barrier (BBB) penetration efficiency, a narrow treatment time window and drug side effects. Recent studies have pointed out that drug delivery systems based on polymeric nanocarriers can effectively improve the insufficient treatment for ischemic stroke. They can provide neuronal protection by extending the plasma half-life of drugs, enhancing the drug’s permeability to penetrate the BBB, and targeting specific structures and cells. In this review, we classified polymeric nanocarriers used for delivering ischemic stroke drugs and introduced their preparation methods. We also evaluated the feasibility and effectiveness and discussed the existing limitations and prospects of polymeric nanocarriers for ischemic stroke treatment. We hoped that this review could provide a theoretical basis for the future development of nanomedicine delivery systems for the treatment of ischemic stroke. Graphical Abstract

Land subsidence is a worldwide geological hazard. Differential land subsidence has posed the major threat to urban infrastructure, linear rail transit and underground space development and utilization, and also restricted the sustainable development of the economy and society. This paper systematically elaborates on the research progresses on land deformation acquisition, evolution mechanism and simulation of land subsidence, and focuses on the land deformation acquisition technology based on InSAR monitoring and multi-source deformation data fusion, as well as the correlation analysis, statistical analysis, machine learning and other methods to analyze the relationship between the evolution of land subsidence and various influencing factors based on geotechnical experiment and long time series observation data. On this basis, the advantages and disadvantages of land subsidence simulation models such as groundwater flow field-land deformation model, mathematical statistical model and machine learning model are explored. It is found that multi-source deformation data fusion can improve the spatiotemporal resolution of land deformation. The differences in geological structure, lithology, groundwater exploitation, and dynamic and static loads are factors contributing to the differential evolution of land subsidence. The difficulty in balancing the computational efficiency and interpretability of mathematical models for land subsidence is the main problem in simulation. According to the literature review, the current researches mainly focus on land subsidence caused by groundwater over-exploitation. This paper further proposes the future research directions for land subsidence, under the background of climate change, new hydrological condition and dataset, and based on the fusion of data through remote sensing and field observations, integrating the latest progress of InSAR, GeoAI, cloud platform and other technologies to reveal the evolution mechanism of land subsidence considering the climate change and anthropic activities and provide technical support for regional land subsidence prevention and urban safety.

Abstract The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments.

Abstract Myelodysplastic syndromes (MDS) are clonal hematopoietic malignancies and seriously threaten people’s health. Current therapies include bone marrow transplantation and several hypomethylating agents. However, many elderly patients cannot benefit from bone marrow transplantation and many patients develop drug resistance to hypomethylating agents, making it urgent to explore novel therapy. RSL3 can effectively induce ferroptosis in various tumors and combination of RSL3 and hypomethylating agents is promising to treat many tumors. However, its effect in MDS was unknown. In this study, we found that RSL3 inhibited MDS cell proliferation through inducing ROS-dependent apoptosis. RSL3 inhibited Bcl-2 expression and increased caspase 3 and PARP cleavage. RNA-seq analysis revealed that MYB may be a potential target of RSL3. Rescue experiments showed that overexpression of MYB can rescue MDS cell proliferation inhibition caused by RSL3. Cellular thermal shift assay showed that RSL3 binds to MYB to exert its function. Furthermore, RSL3 inhibited tumor growth and decreased MYB and Bcl-2 expression in vivo. More importantly, RSL3 decreased the viability of bone marrow mononuclear cells (BMMCs) isolated from MDS patients, and RSL3 had a synergistic effect with DAC in MDS cells. Our studies have uncovered RSL3 as a promising compound and MYB/Bcl-2 signaling pathway as a potential target for MDS treatment.

Energy-resolved neutron imaging is an effective way to investigate the internal structure and residual stress of materials. Different sample sizes have varying requirements for the detector's imaging field of view (FOV) and spatial resolution. Therefore, a dual-mode energy-resolved neutron imaging detector was developed, which mainly consisted of a neutron scintillator screen, a mirror, imaging lenses, and a time-stamping optical fast camera. This detector could operate in a large FOV mode or a high spatial resolution mode. To evaluate the performance of the detector, the neutron wavelength spectra and the multiple spatial resolution tests were conducted at CSNS. The results demonstrated that the detector accurately measured the neutron wavelength spectra selected by a bandwidth chopper. The best spatial resolution was about 20 μm in high spatial resolution mode after event reconstruction, and a FOV of 45.0 mm × 45.0 mm was obtained in large FOV mode. The feasibility was validated to change the spatial resolution and FOV by replacing the scintillator screen and adjusting the lens magnification.

Abstract Background Successive stamen movement is a complex plant behavior involving successive uplift of stamens and pollen release, which plays a role in reducing sexual interference, increasing pollen deposition and promoting pollen export. Although reported from several taxa, studies on whether the movement can be influenced by abiotic and biotic factors are scarce. Methods In this study, we here for the first time described a pattern of successive stamen movement in Saxifraga candelabrum (Saxifragaceae). We then compared the rates of stamen movement in S. candelabrum under different weather and varying pollinator visits. Pollen packaging and presentation schedule of S. candelabrum were also investigated. Results The results showed that the number of stamens bent per day in sunny days was significantly higher than overcast and rain. Flowers that receive more pollinator visits (control treatment) had significantly higher number of stamen movement than those that received fewer (removal treatment) and none (bagging treatment). Throughout the staminate phase of a flower, there was a progressive increase in both pollen quantity of individual stamens and pollen presentation during each day. Conclusion Our research demonstrates that successive stamen movement in S. candelabrum was accelerated by favorable weather and increased pollinator visits, which may promote pollen export. Moreover, incremental pollen packaging is likely an adaptation to seasonal regularity in variations of sex ratio resulting from protandry.

Abstract Background Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies. Results In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-β/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats. Conclusion In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation. Graphical Abstract

Pancreatic cancer (PC) is a very aggressive digestive system tumor, known for its high mortality rate, low cure rate, low survival rate and poor prognosis. In particular, pancreatic ductal adenocarcinoma (PADC), which accounts for more than 90% of PC cases, has an overall 5-year survival rate of only 5%, which is an extremely critical situation. Early detection and effective treatment of PC is extremely difficult, which leads many patients to despair. In the current medical context, targeted therapy, as an important strategy for cancer treatment, is expected. However, the problems of immune escape and drug resistance in PC have become two major obstacles that are difficult to be overcome by targeted therapy. How to break through these two difficulties has become a key issue to be solved in the field of PC therapy. In recent years, non-coding RNAs (ncRNAs) have continued to heat up in the field of cancer research. NcRNAs play a pivotal role in gene regulation, cell differentiation, development, and disease processes, and their important roles in the genesis, development, and therapeutic response of PC have been gradually revealed. More importantly, ncRNAs have many advantages as therapeutic targets, such as high specificity and low side effects, making them a new favorite in the field of PC therapy. Therefore, the aim of this paper is to provide new ideas and methods for the targeted therapy of PC by reviewing the mechanism of action of four major ncRNAs (circRNAs, lncRNAs, miRNAs, siRNAs) in both immune escape and drug resistance of PC. It is expected that an effective way to overcome immune escape and drug resistance can be found through in-depth study of ncRNA, bringing a ray of hope to PC patients.

CHAC1, an essential regulator of oxidative stress and ferroptosis, is increasingly recognized for its significant roles in these cellular processes and its impact on various human diseases and cancers. This review aims to provide a comprehensive overview of CHAC1’s molecular functions, regulatory mechanisms, and effects in different pathological contexts. Specifically, the study objectives are to elucidate the biochemical pathways involving CHAC1, explore its regulatory network, and discuss its implications in disease progression and potential therapeutic strategies. As a γ-glutamyl cyclotransferase, CHAC1 degrades glutathione, affecting calcium signaling and mitochondrial function. Its regulation involves transcription factors like ATF4 and ATF3, which control CHAC1 mRNA expression. CHAC1 is crucial for maintaining redox balance and regulating cell death pathways in cancer. Its elevated levels are associated with poor prognosis in many cancers, indicating its potential as a biomarker and therapeutic target. Additionally, CHAC1 influences non-cancerous diseases such as neurodegenerative and cardiovascular disorders. Therapeutically, targeting CHAC1 could increase cancer cell sensitivity to ferroptosis, aiding in overcoming resistance to standard treatments. This review compiles current knowledge and recent discoveries, emphasizing CHAC1’s vital role in human diseases and its potential in diagnostic and therapeutic applications.

IntroductionSystemic lupus erythematosus (SLE) is a complex autoimmune disease, and despite the availability of multiple treatments, striking a balance between long-term efficacy and side effects remains a major clinical challenge. B-cell–directed therapy has attracted much attention because of its unique mechanism of action. Belimumab and obinutuzumab, as representative drugs for B-cell–directed therapy, have shown their respective advantages for SLE treatment. However, data on combination therapy with obinutuzumab and belimumab are currently unavailable.Case presentationWe present the severe case report of a patient who was diagnosed with lupus nephritis (LN) with gastrointestinal involvement and developed acute renal failure. The patient responded to the first dose of obinutuzumab but failed to achieve a complete response to LN. The repeated use of obinutuzumab was limited by persistently low IgG levels and frequent infections. This is a real-world challenge that must be addressed. Therefore, the patient was subsequently treated with a novel sequential regimen of obinutuzumab followed by belimumab. After 18 months of follow-up, the patient achieved a complete clinical response with a favourable safety profile, along with the conversion of all autoantibodies from positive to negative and sustained negativity. To date, the patient has achieved a dual clinical and serological response.ConclusionThere is a reason to believe that this novel combination regimen could be developed as a therapeutic strategy, with the expectation of balancing efficacy and safety.

PurposeRhubarb (Rheum palmatum L.) and astragalus (Radix astragali) find widespread used in clinical formulations for treating chronic kidney disease (CKD). Notably, the key active components, total rhubarb anthraquinone (TRA) and total astragalus saponin (TAS), exhibit superiority over rhubarb and astragalus in terms of their clear composition, stability, quality control, small dosage, and efficacy for disease treatment. Additionally, astragalus polysaccharides (APS) significantly contribute to the treatment of renal fibrosis by modulating the gut microbiota. However, due to differences in the biopharmaceutical properties of these components, achieving synergistic effects remains challenging. This study aims to develop combined pellets (CPs) and evaluate the potential effect on unilateral ureteral obstruction (UUO)-induced renal fibrosis.MethodsThe CPs pellets were obtained by combining TRA/TAS-loaded SNEDDS pellets and APS-loaded pellets, prepared using the fluidized bed coating process. The prepared pellets underwent evaluation for morphology, bulk density, hardness, and flowing property. Moreover, the in vitro release of the payloads was evaluated with the CHP Type I method. Furthermore, the unilateral ureteral obstruction (UUO) model was utilized to investigate the potential effects of CPs pellets on renal fibrosis and their contribution to gut microbiota modulation.ResultsThe ex-vivo study demonstrated that the developed CPs pellets not only improved the dissolution of TRA and TAS but also delivered TRA/TAS and APS spatiotemporally to the appropriate site along the gastrointestinal tract. In an animal model of renal fibrosis (UUO rats), oral administration of the CPs ameliorated kidney histological pathology, reduced collagen deposition, and decreased the levels of inflammatory cytokines. The CPs also restored the disturbed gut microbiota induced by UUO surgery and protected the intestinal barrier.ConclusionThe developed CPs pellets represent a promising strategy for efficiently delivering active components in traditional Chinese medicine formulas, offering an effective approach for treating CKD.

We prepared tea tree essential oil microcapsules, and the microcapsules and pullulan were coated on kraft paper to prepare an antibacterial paper. The antibacterial activity, structural characterization, and thermal stability of the prepared microcapsules and packaging paper were then tested. We found that the retention rate of microcapsules reached 87.1% after a 70 min of high-temperature treatment. The minimum inhibitory concentrations of microcapsules to S. aureus and E. coli were 112 mg/mL and 224 mg/mL, and the bacteriostatic zones of the packaging paper to E. coli and S. aureus were 17.49 mm and 22.75 mm, respectively. The prepared microcapsules were irregular. The paper coating was formed via hydrogen bonding, which filled the pores of paper fibers. When compared with the base paper, the roughness of the paper was reduced to 7.16 nm (Rq) and 5.61 nm (Ra), and no thermal decomposition occurred at

Background Ethnicity is not collected routinely in Australian health data. Ancestry data is collected in the Census which is now linked to health data. We aimed to develop an approach to using ancestry data to examine health disparities. Methods An expert panel was formed with representatives from the Federation of Ethnic Communities’ Councils, Australian Bureau of Statistics (ABS) and researchers. The work was also informed by a community panel and yarning circles led by Aboriginal and Torres Strait Islander academics. We analysed 2016 Census data linked to death registrations for 2016-2021 in 20.9 million people and compared how different approaches to categorising ethnicity impacted on detection of health inequalities between groups. Results We developed the following approach: (1) Recategorise those reporting Australian only or New Zealand only ancestry from the Oceania to the European category; (2) For those reporting two ancestries: prioritise ethnic minority over national identities (e.g. Australian) and for the remainder create multiethnic groups based on the combined ancestries; (3) First analyse data at the maximum level of granularity, but then collapse up granularity where no disparities are identified to simplify results and messaging. Analysis of mortality data demonstrated that these approaches improved identification of ethnic mortality inequalities. Discussion We developed a set of principles to use Australian Census Ancestry data to identify health disparities by ethnicity. The recommendations facilitate harnessing valuable Census data to identify important health disparities and better inform future health policy in Australia.

Background: Ovarian cancer (OV) is regarded as one of the most lethal malignancies affecting the female reproductive system, with individuals diagnosed with OV often facing a dismal prognosis due to resistance to chemotherapy and the presence of an immunosuppressive environment. T cells serve as a crucial mediator for immune surveillance and cancer elimination. This study aims to analyze the mechanism of T cell-associated markers in OV and create a prognostic model for clinical use in enhancing outcomes for OV patients. Methods: Based on the single-cell dataset GSE184880, this study used single-cell data analysis to identify characteristic T cell subsets. Analysis of high dimensional weighted gene co-expression network analysis (hdWGCNA) is utilized to identify crucial gene modules along with their corresponding hub genes. A grand total of 113 predictive models were formed utilizing ten distinct machine learning algorithms along with the combination of the cancer genome atlas (TCGA)-OV dataset and the GSE140082 dataset. The most dependable clinical prognostic model was created utilizing the leave one out cross validation (LOOCV) framework. The validation process for the models was achieved by conducting survival curve analysis and receiver operating characteristic (ROC) analysis. The relationship between risk scores and immune cells was explored through the utilization of the Cibersort algorithm. Additionally, an analysis of drug sensitivity was carried out to anticipate chemotherapy responses across various risk groups. The genes implicated in the model were authenticated utilizing qRT-PCR, cell viability experiments, and EdU assay. Results: This study developed a clinical prognostic model that includes ten risk genes. The results obtained from the training set of the study indicate that patients classified in the low-risk group experience a significant survival advantage compared to those in the high-risk group. The ROC analysis demonstrates that the model holds significant clinical utility. These results were verified using an independent dataset, strengthening the model's precision and dependability. The risk assessment provided by the model also serves as an independent prognostic factor for OV patients. The study also unveiled a noteworthy relationship between the risk scores calculated by the model and various immune cells, suggesting that the model may potentially serve as a valuable tool in forecasting responses to both immune therapy and chemotherapy in ovarian cancer patients. Notably, experimental evidence suggests that PFN1, one of the genes included in the model, is upregulated in human OV cell lines and has the capacity to promote cancer progression in in vitro models. Conclusion: We have created an accurate and dependable clinical prognostic model for OV capable of predicting clinical outcomes and categorizing patients. This model effectively forecasts responses to both immune therapy and chemotherapy. By regulating the immune microenvironment and targeting the key gene PFN1, it may improve the prognosis for high-risk patients.

BackgroundCOVID-19 vaccines are crucial for reducing the threat and burden of the pandemic on global public health, yet the epigenetic, especially RNA editing in response to the vaccines remains unelucidated.ResultsOur current study performed an epitranscriptomic analysis of RNA-Seq data of 260 blood samples from 102 healthy and SARS-CoV-2 naïve individuals receiving different doses of the COVID-19 vaccine and revealed dynamic, transcriptome-wide adenosine to inosine (A-to-I) RNA editing changes in response to COVID-19 vaccines (RNA editing in response to COVID-19 vaccines). 5592 differential RNA editing (DRE) sites in 1820 genes were identified, with most of them showing up-regulated RNA editing and correlated with increased expression of edited genes. These deferentially edited genes were primarily involved in immune- and virus-related gene functions and pathways. Differential ADAR expression probably contributed to RNA editing in response to COVID-19 vaccines. One of the most significant DRE in RNA editing in response to COVID-19 vaccines was in apolipoprotein L6 (APOL6) 3’ UTR, which positively correlated with its up-regulated expression. In addition, recoded key antiviral and immune-related proteins such as IFI30 and GBP1 recoded by missense editing was observed as an essential component of RNA editing in response to COVID-19 vaccines. Furthermore, both RNA editing in response to COVID-19 vaccines and its functions dynamically depended on the number of vaccine doses.ConclusionOur results thus underscored the potential impact of blood RNA editing in response to COVID-19 vaccines on the host’s molecular immune system.

BackgroundAn escalating body of clinical trials and observational studies hints at a plausible link between gut flora and postpartum depression (PPD). The definitive causal dynamics between these two entities remain shrouded in ambiguity. Therefore, in this study, we employed the two-sample Mendelian randomization approach to ascertain the causal link between gut microbiota and PPD.MethodsSummary-level GWAS data related to the human gut microbiota were obtained from the international consortium MiBioGen and the Dutch Microbiome Project (species). For PPD, GWAS data were derived from the FinnGen biobank, consisting 57,604 cases and 596,601 controls. The inverse variance weighted method (IVW) as the cornerstone of our analytical approach. Subsequent to this, a comprehensive suite of tests for pleiotropy and heterogeneity were conducted to ensure the reliability and robustness of our findings.ResultsWe identified 12 bacterial taxa associated with the risk of PPD. Veillonellaceae, Ruminococcaceae UCG 011, Bifidobacterium adolescentis, Paraprevotella clara, Clostridium leptum, Eubacterium siraeum, Coprococcus catus exhibited an inversely associated with the risk of PPD. Alphaproteobacteria, Roseburia, FamilyXIIIAD3011group, Alistipes onderdonkii, Bilophila wadsworthia showed a positive correlation with the risk of PPD.LimitationsThe GWAS data derived from the MiBioGen consortium, DMP, and FinnGen consortium, may introduce selection bias. Moreover, the data primarily originates from European populations, hence extrapolating these results to diverse populations should be approached with caution. The etiological factors behind PPD remain enigmatic, alluding to the existence of potential undisclosed confounders.ConclusionBased on this MR analysis, we found a causal relationship between certain gut microbial communities and PPD. Future clinical studies can further explore the treatment of PPD through the combined use of microorganisms. This not only offers insights into the pathogenesis of PPD but also lays the foundation for utilizing gut microbiota as biotherapeutics in treating neurological disorders.

Abstract Understanding water saturation levels in tight gas carbonate reservoirs is vital for optimizing hydrocarbon production and mitigating challenges such as reduced permeability due to water saturation (Sw) and pore throat blockages, given its critical role in managing capillary pressure in water drive mechanisms reservoirs. Traditional sediment characterization methods such as core analysis, are often costly, invasive, and lack comprehensive spatial information. In recent years, several classical machine learning models have been developed to address these shortcomings. Traditional machine learning methods utilized in reservoir characterization encounter various challenges, including the ability to capture intricate relationships, potential overfitting, and handling extensive, multi-dimensional datasets. Moreover, these methods often face difficulties in dealing with temporal dependencies and subtle patterns within geological formations, particularly evident in heterogeneous carbonate reservoirs. Consequently, despite technological advancements, enhancing the reliability, interpretability, and applicability of predictive models remains imperative for effectively characterizing tight gas carbonate reservoirs. This study employs a novel data-driven strategy to prediction of water saturation in tight gas reservoir powered by three recurrent neural network type deep/shallow learning algorithms—Gated Recurrent Unit (GRU), Recurrent Neural Networks (RNN), Long Short-Term Memory (LSTM), Support Vector Machine (SVM), K-nearest neighbor (KNN) and Decision tree (DT)—customized to accurately forecast sequential sedimentary structure data. These models, optimized using Adam's optimizer algorithm, demonstrated impressive performance in predicting water saturation levels using conventional petrophysical data. Particularly, the GRU model stood out, achieving remarkable accuracy (an R-squared value of 0.9973) with minimal errors (RMSE of 0.0198) compared to LSTM, RNN, SVM, KNN and, DT algorithms, thus showcasing its proficiency in processing extensive datasets and effectively identifying patterns. By achieving unprecedented accuracy levels, this study not only enhances the understanding of sediment properties and fluid saturation dynamics but also offers practical implications for reservoir management and hydrocarbon exploration in complex geological settings. These insights pave the way for more reliable and efficient decision-making processes, thereby advancing the forefront of reservoir engineering and petroleum geoscience.

Ogura cytoplasmic male sterility (Ogura CMS) is extensively applied in hybrid seed production in cruciferous crops. However, the post-transcriptional molecular basis of Ogura CMS in cruciferous crops remains elusive. Here, a data-independent acquisition-based proteomic approach coupled with a parallel reaction monitoring-based targeted proteomic assay was used to analyze the proteome dynamics of Ogura CMS cabbage line RM and its maintainer line RF during floral bud development to obtain insights into the mechanism underlying Ogura CMS in cruciferous crops. A total of 9 162 proteins corresponding to 61 464 peptides were identified in RM and RF floral buds. The proteomic fluctuation of RM was weaker than that of RF. Differences in protein expression between RM and RF gradually enlarged with floral bud development. Fifteen continually up-regulated and eight continually down-regulated proteins were found in RM relative to RF throughout floral bud development. Differentially expressed proteins between RM and RF during floral bud development were implicated in the endoplasmic reticulum (ER)-associated protein processing pathway, in which most of them exhibited down-regulated expression in RM. These data suggest that ER-associated protein processing may be involved in pollen abortion in Ogura CMS cabbage by inhibiting the expression of critical factors. Our findings not only deepen the understanding of the molecular mechanisms of Ogura CMS in cruciferous crops but also provide better guidance for applying Ogura CMS in the hybrid breeding of cruciferous crops.

Abstract Ophthalmic manifestations have recently been observed in acute and post-acute complications of COVID-19 caused by SARS-CoV-2 infection. Our precious study has shown that host RNA editing is linked to RNA viral infection, yet ocular adenosine to inosine (A-to-I) RNA editing during SARS-CoV-2 infection remains uninvestigated in COVID-19. Herein we used an epitranscriptomic pipeline to analyze 37 samples and investigate A-to-I editing associated with SARS-CoV-2 infection, in five ocular tissue types including the conjunctiva, limbus, cornea, sclera, and retinal organoids. Our results revealed dramatically altered A-to-I RNA editing across the five ocular tissues. Notably, the transcriptome-wide average level of RNA editing was increased in the cornea but generally decreased in the other four ocular tissues. Functional enrichment analysis showed that differential RNA editing (DRE) was mainly in genes related to ubiquitin-dependent protein catabolic process, transcriptional regulation, and RNA splicing. In addition to tissue-specific RNA editing found in each tissue, common RNA editing was observed across different tissues, especially in the innate antiviral immune gene MAVS and the E3 ubiquitin-protein ligase MDM2. Analysis in retinal organoids further revealed highly dynamic RNA editing alterations over time during SARS-CoV-2 infection. Our study thus suggested the potential role played by RNA editing in ophthalmic manifestations of COVID-19, and highlighted its potential transcriptome impact, especially on innate immunity.

Summary: Background: Labiaplasty is one of the top cosmetic procedures patients are seeking in the past two years. However, treatment of disease in posterior fourchette caused by various etiological factors was less investigated and neglected. Methods: Three types of posterior fourchette deformity were proposed: (1) Redundant posterior fourchette, (2) Relaxed posterior fourchette, and (3) Constricted posterior fourchette. Local flap transfer technique was applied. Y–V-plasty and 5-Z-Flap-plasty were used to treat web type and tight type of the constricted posterior fourchette, respectively. Follow-ups were arranged on the Internet or at the outpatient clinic. Visual analogue scale (VAS) was utilized to evaluate sexual discomfort in the satisfaction questionnaires during follow-up. Results: A total of 48 patients with constricted posterior fourchette deformity from May 2022 to May 2023 were reviewed in the study. Y–V-plasty could decrease VAS in patients with web-type deformity by 4.13 ± 1.46 (p＜0.001). 5-Z-Flap-plasty could decrease VAS in patients with tight-type deformity by 3.76 ± 1.53 (p＜0.05). Satisfaction rates of the web type and tight type were 93.1% (27/29) and 86.7% (13/15) respectively. Complications include two cases of hematoma, one case of persistent pain and two cases of dehiscence. Conclusion: Constricted posterior fourchette seriously affects the quality of life. Y–V-plasty and 5-Z-Flap-plasty can be utilized to treat the two subtypes of constricted posterior fourchette, which can effectively reduce the pain score of patients with high satisfaction and few long-term complications.

In order to make the active ingredients and flavor substances of fruit juice after sterilization treatment closer to the original freshly squeezed fruit juice, the compound juice was prepared with kiwifruit, pineapple and mango as raw materials in this paper. The effects of ultra-high pressure and heat treatment (85 ℃, 5 min) on the quality and shelf life of freshly squeezed compound juice were compared. The results showed that, as the volume ratio of the mixed juice was Vpineapple pulp:Vkiwi pulp:Vmango pulp=4:2:4, the pH, b* value and soluble solid content of the juice treated at 450 MPa, 25 ℃ and 15 min of ultra-high pressure had no significant difference (P>0.05) with the traditional heat treatment, but the loss of vitamin C content and polyphenol content decreased by 12.1% and 17.5%, respectively. By analyzing the main volatile components of the compound juice, it was found that the loss of flavor substances such as enes, esters, alcohols, ketones, and aldehydes in the UHP treatment juice was significantly less than that in the heat treatment juice (P

Abstract Background Sequencing the mitochondrial genome has been increasingly important for the investigation of primary mitochondrial diseases (PMD) and mitochondrial genetics. To overcome the limitations originating from PCR-based mtDNA enrichment, we set out to develop and evaluate a PCR-independent approach in this study, named Pime-Seq (PCR-independent mtDNA enrichment and next generation Sequencing). Results By using the optimized mtDNA enrichment procedure, the mtDNA reads ratio reached 88.0 ± 7.9% in the sequencing library when applied on human PBMC samples. We found the variants called by Pime-Seq were highly consistent among technical repeats. To evaluate the accuracy and reliability of this method, we compared Pime-Seq with lrPCR based NGS by performing both methods simultaneously on 45 samples, yielding 1677 concordant variants, as well as 146 discordant variants with low-level heteroplasmic fraction, in which Pime-Seq showed higher reliability. Furthermore, we applied Pime-Seq on 4 samples of PMD patients retrospectively, and successfully detected all the pathogenic mtDNA variants. In addition, we performed a prospective study on 192 apparently healthy pregnant women during prenatal screening, in which Pime-Seq identified pathogenic mtDNA variants in 4 samples, providing extra information for better health monitoring in these cases. Conclusions Pime-Seq can obtain highly enriched mtDNA in a PCR-independent manner for high quality and reliable mtDNA deep-sequencing, which provides us an effective and promising tool for detecting mtDNA variants for both clinical and research purposes.

Abstract Background Ginger is a common aromatic vegetable with a wide range of functional ingredients and considerable medicinal and nutritional properties. Numerous studies have shown that ginger and its active ingredients have suppressive effects on manifold tumours, including ovarian cancer (OC). However, the molecular mechanism by which ginger inhibits OC is not clear. The aim of this study was to investigate the function and mechanism of ginger in OC. Methods The estimation of n6-methyladenosine (m6A) levels was performed using the m6A RNA Methylation Quantification Kit, and RT-qPCR was used to determine the expression of m6A-related genes and proteins. The m6A methylationome was detected by MeRIP-seq, following analysis of the data. Differential methylation of genes was assessed utilizing RT-qPCR and Western Blotting. The effect of ginger on SKOV3 invasion in ovarian cancer cells was investigated using the wound healing assay and transwell assays. Results Ginger significantly reduced the m6A level of OC cells SKOV3. The 3’UTR region is the major site of modification for m6A methylation, and its key molecular activities include Cell Adhesion Molecules, according to meRIP-seq results. Moreover, it was observed that Ginger aids significantly in downregulating the CLDN7, CLDN11 mRNA, and protein expression. The results of wound healing assay and transwell assay showed that ginger significantly inhibited the invasion of OC cells SKOV3. Conclusions Ginger inhibits ovarian cancer cells’ SKOV3 invasion by regulating m6A methylation through CLDN7, CLDN11, and CD274.

Owing to the extensive production and utilization of plastic products, a substantial volume of plastic waste is inevitably generated, comprising plastic particles < 5 mm in size, which are categorized as microplastics. Microplastics emanating from diverse sources can be classified as primary and secondary. Primary microplastics encompass plastic particles with a diameter < 5 mm that are synthetically produced in industrial processes, such as plastic microbeads found in exfoliating scrubs, toothpaste, and facial cleansers. Secondary microplastics result from mechanical abrasion, ultraviolet radiation, biological fragmentation, and other processes acting on larger plastic items. Surveys have revealed the global distribution of microplastics, aptly termed the "PM2.5 of the ocean." Microplastics are a prominent environmental issue, paralleling challenges posed by climate change, ozone depletion, and ocean acidification as an emerging global concern. Consequently, their pollution characteristics and associated ecological and environmental risks have become focal points of global research. Marine microplastics originate predominantly from atmospheric deposition, land-based inputs, coastal tourism, maritime shipping, and fishery production. Seabed sediments serve as a significant reservoir or "sink" for microplastics in oceans. Disparities in microplastic abundance are evident in nearshore beaches, offshore sediments, and deep ocean sediments. The pollution status of microplastics in sediments may be exacerbated in urban nearshore areas owing to intense human activities. However, the status and distribution characteristics of microplastics in urban nearshore sediments remain unclear. Qingdao is a typical coastal and marine city. In this study, we investigated the abundance, morphology, polymer types, and color of microplastics in the surface sediments of the Laoshan coastal area of Qingdao. Microplastics were isolated from surface sediment samples and examined under a stereomicroscope equipped with a camera. Fourier-transform infrared spectroscopy was employed to identify the polymer types of microplastics. The results revealed that the abundance of microplastics in the surface sediments of the Laoshan coastal area of Qingdao ranged from 9.06–34.48 ind./kg with an average of (21.97±8.32) ind./kg. Microplastics with particle sizes < 0.5 mm constituted 76% of the total microplastic count. Fiber, granule, and film shapes were predominant, accounting for 53%, 33%, and 14%, respectively. Transparent microplastics were more prevalent than other colors, accounting for 66% of the total. Four polymer types of microplastics were identified: Polypropylene (PP), polystyrene (PS), cellulose, and polyethylene. PP was the dominant polymer type, representing 45%, followed by PS (22%). The microplastic pollution levels in the surface sediments of the Laoshan coastal area of Qingdao were found to be comparatively lower than those in other domestic sea sediments. Considering the heightened human activity in coastal cities, further investigation of the microplastic pollution status and distribution characteristics in coastal areas is warranted. These findings contribute to an enhanced understanding of the environmental risks posed by microplastics to marine ecosystems and provide a scientific foundation for the assessment and management of microplastic pollution in coastal regions.

The Bohai Sea, which is China's only semi-enclosed inland sea, has received significant inputs of heavy metals from the rapidly industrializing and urbanizing Bohai Sea Economic Rim. Because of the limited water exchange and self-purification capacity, heavy metal pollution in the Bohai Sea has been intensifying, making it a focal area of heavy metal pollution research. Furthermore, the Bohai Sea serves as one of China's traditional fishing grounds, acting as both a spawning area and foraging ground for various economically significant fishery species, thereby providing abundant seafood for urban and rural communities in the Bohai Sea region. Heavy metals are considered one of the principal pollutants in the marine environment of the Bohai Sea due to their high accumulation and resistance to degradation. They accumulate within organisms and are subsequently transferred through the food chain, resulting in pollution of marine biological resources. The issue of heavy metal pollution in the Bohai Sea has raised concerns among researchers regarding food product safety and human health risks.To assess the status of heavy metal pollution in fish species from the Bohai Sea, we randomly selected 144 samples from 10 different fish species collected during a fisheries resource survey in the Bohai Sea region. All fish samples were stored frozen at –20℃ until further analysis. The collected samples were thawed at room temperature, dissected to obtain muscle tissues, freeze-dried, and subsequently ground into a fine powder using agate mortar. Approximately 0.2 to 0.5 g of the homogenized samples were digested using a microwave digestion system with 2.5 mL of concentrated H2SO4, 4.0 mL of concentrated HNO3, and 1.5 mL of H2O2. The concentrations of heavy metals, i.e., Cu, Zn, Pb, Cr, Cd, and As, were determined using inductively coupled plasma mass spectrometry (ICP-MS). To estimate inorganic As (iAs) in fish muscle from the Bohai Sea, we used the highest reported percentage of iAs in the total As, which was 6.88%, as observed in the literature. The study assessed the single-element pollution and comprehensive heavy metal pollution in Bohai Sea fish using the single factor pollution index, Nemerow comprehensive pollution index (PN), and metal pollution index (MPI). To evaluate the dietary risk posed by heavy metal-contaminated fish, we introduced daily intake (DI) and target hazard quotient (THQ) as assessment indicators. DI represents the daily intake of heavy metals from fish consumption, whereas THQ indicates the potential health risk of ingesting heavy metals.The fish samples collected for this study belonged to 10 different species: Setipinna taty, Scomberomorus niphonius, Pampus argenteus, Trichiurus lepturus, Eupleurogrammus muticus, Engraulis japonicus, Cynoglossus joyneri, Thryssa kammalensis, Liparis tanakae, and Enedrias fangi. The mean values of heavy metal concentrations in the muscle tissues of Bohai Sea fish were as follows: Cu (0.702±0.680) mg/kg, Zn (9.697±5.279) mg/kg, Pb (0.035±0.059) mg/kg, Cr (0.029±0.035) mg/kg, Cd (0.093±0.091) mg/kg, and As (0.959±0.813) mg/kg. When we compared the heavy metal content in fish from the Bohai Sea with those from other sea regions, our findings indicated that there are notable differences in heavy metal levels among fish species in various sea areas of China. Fish from the Bohai Sea exhibit relatively higher levels of Cu, Zn, and As. The single-element pollution index for Cu, Pb, Cd, Cr, and iAs ranged from 0.003 to 0.056, 0.003 to 0.165, 0.021 to 0.767, 0.017 to 0.085, and 0.059 to 0.373, respectively. Some fish samples displayed Cd or iAs contamination, indicating that Cd and iAs were the major contributors to heavy metal pollution in Bohai Sea fish. The PN for the 10 fish species in the Bohai Sea ranged from 0.185 to 1.210, with lionfish exhibiting the highest PN value, signifying severe contamination. The MPI ranged from 0.022 to 0.097, with bluefin trevally, lionfish, and tongue sole having similar and higher MPI values compared to other species. The results of the dietary risk assessment showed that the daily intake of heavy metals (Cu, Zn, Pb, Cd, Cr, and iAs) from consuming Bohai Sea fish was relatively low, and it was below the maximum allowable intake levels established by the Food and Agriculture Organization (FAO) of the United Nations, the World Health Organization (WHO), and the National Research Council (NRC) for Zn, Cu, Pb, Cd, iAs, or Cr. The THQ values for single heavy metals and THQS for multiple heavy metals were all less than 1.0, indicating that consuming Bohai Sea fish is unlikely to pose health risks to consumers. Different heavy metals had varying contributions to THQs, with the average THQ values for Bohai Sea fish species ranking as follows: Pb (0.0029) < Cu (0.0059) < Cd (0.0098) < Cr (0.0105) < Zn (0.0113) < iAs (0.0733).Our findings contribute to a deeper understanding of the heavy metal pollution status in Bohai Sea fishery biota. Additionally, they provide a crucial scientific foundation for ensuring the safety of seafood products from the Bohai Sea. Furthermore, this study offers valuable insights for consumers, enabling the provision of more informed dietary recommendations.

Objective To establish an effective quality indicator monitoring system, scientifically and objectively evaluate the quality management level of blood banks, and achieve continuous improvement of quality management in blood bank. Methods A quality monitoring indicator system that covers the whole process of blood collection and supply was established, the questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong. Statistical analysis of 21 quality monitoring indicators in terms of blood donation service (10 indicators), blood component preparation (7 indicators ), and blood supply (4 indicators) from each blood bank from January to December 2022 were conducted using SPSS25.0 software The differences in quality monitoring indicators of blood banks of different scales were analyzed. Results The average values of quality monitoring indicators for blood donation service process of 17 blood banks were as follows: 44.66% (2 233/5 000) of regular donors proportion, 0.22% (11/50) of adverse reactions incidence, 0.46% (23/5 000) of non-standard whole blood collection rate, 0.052% (13/25 000) of missed HBsAg screening rate, 99.42% (4 971/5 000) of first, puncture successful rate, 86.49% (173/200) of double platelet collection rate, 66.50% (133/200) of 400 mL whole blood collection rate, 99.25% (397/400) of donor satisfaction rate, 82.68% (2 067/2 500) of use rate of whole blood collection bags with bypass system with sample tube, and 1 case of occupational exposure in blood collection.There was a strong positive correlation between the proportion of regular blood donors and the collection rate of 400 mL whole blood (P

Objective To objectively evaluate the quality control level of blood testing process in blood banks through quantitative monitoring and trend analysis, and to promote the homogenization level and standardized management of blood testing laboratories in blood banks. Methods A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation service, blood component preparation, blood testing, blood supply and quality control was established. The questionnaire Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong province. Quality monitoring indicators of each blood bank from January to December 2022 were collected, and 31 indicators in terms of blood testing were analyzed using SPSS25.0 software. Results The proportion of unqualified serological tests in 17 blood bank laboratories was 55.84% for ALT, 13.63% for HBsAg, 5.08% for anti HCV, 5.62% for anti HIV, 18.18% for anti TP, and 1.65% for other factors (mainly sample quality). The detection unqualified rate and median were (1.23±0.57)% and 1.11%, respectively. The ALT unqualified rate and median were (0.74±0.53)% and 0.60%, respectively. The detection unqualified rate was positively correlated with ALT unqualified rate (r=0.974, P0.05), while the outrage rate was positively correlated with the usage rate (r=0.592, P

Objective To establish an effective quality monitoring indicator system for blood quality control in blood banks, in order to analyze the quality control indicators for blood collection and supply, and evaluate blood quality control process, thus promoting continuous improvement and standardizing management of blood quality control in blood banks. Methods A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation services, component preparation, blood testing, blood supply and quality control was established. The Questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process was distributed to 17 blood banks in Shandong, which clarified the definition and calculation formula of indicators. The quality monitoring indicator data from January to December 2022 in each blood bank were collected, and 20 quality control indicators data were analyzed by SPSS25.0 software. Results The average pass rate of key equipment monitoring, environment monitoring, key material monitoring, and blood testing item monitoring of 17 blood banks were 99.47%, 99.51%, 99.95% and 98.99%, respectively. Significant difference was noticed in the pass rate of environment monitoring among blood banks of varied scales(P

Objective To establish a blood quality monitoring indicator system, in order to continuously improve blood quality and standardized management. Methods Based on the research of literature and standards, and guided by the key control points of blood collection and supply process, the blood quality monitoring indicator system was developed. Through two rounds of Delphi expert consultation, the indicator content was further revised and improved according to expert opinions after six months of trial implementation. The indicator weight was calculated by questionnaire and analytic hierarchy process. Results A blood quality monitoring indicator system covering the whole process of blood collection and supply was constructed, including five primary indicators, namely blood donation service, blood component preparation, blood testing, blood supply and quality control, as well as 72 secondary indicators, including definitions, calculation formulas, etc. Two rounds of expert consultation and two rounds of feasibility study meeting were held to revise 17 items and the weight of each indicator was obtained through the analytic hierarchy process. After partial adjustments, a blood quality monitoring indicator system was formed. Conclusion A blood quality monitoring indicator system covering the whole process of blood collection and supply has been established for the first time, which can effectively evaluate the quality management level of blood banks and coordinate blood quality control activities of blood banks in Shandong like pieces in a chess game, thus improving the standardized management level

Abstract Background The aim of this study was to develop a nomogram by combining chest computed tomography (CT) images and clinicopathological predictors to assess the survival outcomes of patients with primary pulmonary lymphoepithelial carcinoma (PLEC). Methods 113 patients with stage I–IV primary PLEC who underwent treatment were retrospectively reviewed. The Cox regression analysis was performed to determine the independent prognostic factors associated with patient’s disease-free survival (DFS) and cancer-specific survival (CSS). Based on results from multivariate Cox regression analysis, the nomograms were constructed with pre-treatment CT features and clinicopathological information, which were then assessed with respect to calibration, discrimination and clinical usefulness. Results Multivariate Cox regression analysis revealed the independent prognostic factors for DFS were surgery resection and hilar and/or mediastinal lymphadenopathy, and that for CSS were age, smoking status, surgery resection, tumor site in lobe and necrosis. The concordance index (C‑index) of nomogram for DFS and CSS were 0.777 (95% CI: 0.703–0.851) and 0.904 (95% CI: 0.847–0.961), respectively. The results of the time‑dependent C‑index were internally validated using a bootstrap resampling method for DFS and CSS also showed that the nomograms had a better discriminative ability. Conclusions We developed nomograms based on clinicopathological and CT factors showing a good performance in predicting individual DFS and CSS probability among primary PLEC patients. This prognostic tool may be valuable for clinicians to more accurately drive treatment decisions and individualized survival assessment.

Abstract Background Benign paroxysmal positional vertigo (BPPV) is a prevalent form of vertigo that necessitates a skilled physician to diagnose by observing the nystagmus and vertigo resulting from specific changes in the patient’s position. In this study, we aim to explore the integration of eye movement video and position information for BPPV diagnosis and apply artificial intelligence (AI) methods to improve the accuracy of BPPV diagnosis. Methods We collected eye movement video and diagnostic data from 518 patients with BPPV who visited the hospital for examination from January to March 2021 and developed a BPPV dataset. Based on the characteristics of the dataset, we propose a multimodal deep learning diagnostic model, which combines a video understanding model, self-encoder, and cross-attention mechanism structure. Result Our validation test on the test set showed that the average accuracy of the model reached 81.7%, demonstrating the effectiveness of the proposed multimodal deep learning method for BPPV diagnosis. Furthermore, our study highlights the significance of combining head position information and eye movement information in BPPV diagnosis. We also found that postural and eye movement information plays a critical role in the diagnosis of BPPV, as demonstrated by exploring the necessity of postural information for the diagnostic model and the contribution of cross-attention mechanisms to the fusion of postural and oculomotor information. Our results underscore the potential of AI-based methods for improving the accuracy of BPPV diagnosis and the importance of considering both postural and oculomotor information in BPPV diagnosis.

Abstract Background Nutrition and exercise are important interventions for sarcopenia. There were few studies on oral oligopeptide nutrition preparations combined with exercise to intervene in the older people with sarcopenia. The aim of this study was to verify the effectiveness of oligopeptide nutrition preparation combined with exercise intervention on the older people with sarcopenia in community. Methods A total of 219 subjects aged 65 years or older with sarcopenia were randomly divided into 4 groups. The nutrition group (n = 58) was given individualized nutrition education and oral oligopeptide nutrition preparation. The exercise group (n = 50) received exercise intervention. The combined group (n = 52) received both oral nutrition preparation and exercise interventions. The control group (n = 59) only received individualized nutrition education. The nutrition preparation can provide energy 185kcal and protein 24.2g per day. The exercise intervention including warm-up exercise, resistance exercise and aerobic exercise, the training time was 60min for 5 times every week. The intervention lasted for 16 weeks. Hand grip strength, gait speed, body composition and hematology parameters were measured before and after intervention. Results A total of 159 subjects completed the study. Compared with baseline, the left grip strength and 6-m walking speed of the subjects in nutrition group increased significantly after the intervention, and the grip strength of both hands in exercise group and combined group increased significantly. The body weight of the subjects in nutrition group, exercise group and combined group increased significantly after intervention, but no increase in soft lean mass (SLM) and skeletal muscle mass (SMM) was observed in any of the four groups. The fat-free mass (FFM) of the legs of the control group, exercise group and nutrition group decreased after intervention, and only the FFM of the legs of the combined group maintained the level before the intervention. Conclusion Both oral peptide nutrition and exercise interventions can improve the muscle strength or function of the older people with sarcopenia. However, there were no increases in muscle mass observed. Trial registration ChiCTR, ChiCTR2100052135. Registered 20 October 2021, https://www.chictr.org.cn/showproj.html?proj=135743