Two three-dimensional coordination polymers as fluorescence probes for the detection of nitrobenzene, tetracycline, fluazinam and their application in green pepper.

Two coordination polymers (CPs), [Zn5(L)2(phen)5](1) and [Cd2(HL)(2,2-bpy)(H2O)3](2), were synthesized by using 2',3,3',5,5'-Diphenyl ether pentacarboxylic acid (H5L), phenanthroline (phen), and 2,2'-bipyridine (2,2'-bpy) under hydrothermal conditions. The L5- ligand adopts the µ6-к2: к2: к1: к1: к1: к1 mode in 1 and the µ5-к2: к2: к2: к2: к1 mode in 2. Sensing experiments show that 1 and 2 are fluorescence probes with high sensitivity and rapid detection of nitro explosives, antibiotics, and pesticides. In order to verify the ability of 2 to detect FLU in actual samples, we performed a spiked recovery experiment in green pepper water. The spiked recoveries were 97.77-101.18 %. Interestingly, because H5L is not completely deprotonated in 2, there is abundant hydrogen bonding, which makes the fluorescence quenching rate higher and the detection limit lower. The possible fluorescence quenching mechanism of 1 and 2 can be explained by their UV-VIS absorption spectra and orbital energy levels.

[Research strategy for homogenization feeding of Chinese patent medicines].

Chinese patent medicine constitutes a vital segment of the traditional Chinese medicine(TCM) industry and stands as a significant emblem of TCM modernization. At present, the quality stability between batches of Chinese patent medicine preparations has become a pivotal factor directly restricting the high-quality development of the TCM industry. Consequently, addressing the homogeneity of Chinese patent medicines, this paper proposes a research scheme of homogenization feeding. It systematically elaborates on the object and pretreatment of homogenization, operational procedures of homogenization feeding, selection of homogenization evaluation indices, homogenization feeding algorithm, and homogenization feeding process. With the key quality control indicators as the homogenization target, the homogenization feeding process and its quality analysis were discussed. Finally, a demonstration strategy for homogenization feeding of Chinese patent medicine was formed, providing the scientific basis for advancing the research of quality consistency across batches of Chinese patent medicine preparations.

Simultaneous labial and lingual augmented corticotomy assisted presurgical orthodontics in class III patients: the morphological aspects of the mandibular anterior ridge with cone-beam computed tomography.

OBJECTIVES: This study aims to investigate the changes in alveolar bone following the simultaneous performance of labial and lingual augmented corticotomy (LLAC) in patients with insufficient alveolar bone thickness on both the labial and lingual sides of the mandibular anterior teeth during presurgical orthodontic treatment. MATERIALS AND METHODS: Thirth-five surgical patients with skeletal Class III malocclusion were included: 19 (LLAC group) accepted LLAC surgery during presurgical orthodontic treatment, and 16 (non-surgery group, NS) accepted traditional presurgical orthodontic treatment. Cone-beam computed tomography (CBCT) scans were obtained before treatment (T0) and at the completion of presurgical orthodontic treatment (T1). The amount of vertical alveolar bone and contour area of the alveolar bone in the labial and lingual sides of mandibular incisors were measured. RESULTS: After presurgical orthodontic treatment, the contour area of the alveolar bone at each level on the lingual side and alveolar bone level on both sides decreased significantly in the NS group (P < 0.001). However, the labial and lingual bone contour area at each level and bone level increased significantly in the LLAC group (P < 0.001). The bone formation rate in the lingual apical region was the highest, significantly different from other sites (P < 0.001). CONCLUSIONS: During presurgical orthodontic treatment, LLAC can significantly increase the contour area of the labio-lingual alveolar bone in the mandibular anterior teeth to facilitate safe and effective orthodontic decompensation in skeletal Class III patients. CLINICAL RELEVANCE: This surgery has positive clinical significance in patients lacking bone thickness (< 0.5 mm) in the labial and lingual sides of the lower incisors.

Effect of postoperative normothermic intraperitoneal chemotherapy on the prognosis of MPM patients receiving CRS+HIPEC: A single-center case-control study.

BACKGROUND: The comprehensive treatment strategy, mainly cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), combined with systemic and intraperitoneal chemotherapy, is the standard treatment for malignant peritoneal mesothelioma (MPM), which can significantly prolong the survival of patients. The aim of this study is to investigate the clinical significance of postoperative normothermic intraperitoneal chemotherapy (NIPEC) in MPM patients. METHODS: Data of 152 MPM patients who underwent CRS + HIPEC and postoperative intravenous chemotherapy were retrospectively analyzed. Patients were divided into the Non-NIPEC group and the NIPEC group according to whether they received NIPEC after surgery. The baseline characteristics of the two groups were compared, and the survival outcome was analyzed in subgroups according to completeness of cytoreduction (CC) score. Multivariate survival analysis was used to determine the independent prognostic factors. RESULTS: In CC 0-1 and CC 2-3 subgroups, there was no significant difference in baseline characteristics between Non-NIPEC and NIPEC groups. Survival analysis showed that for CC 0-1 patients, there was no significant difference in overall survival (OS) between Non-NIPEC and NIPEC groups (P = 0.503). However, for CC 2-3 patients, the median OS of the NIPEC group was significantly longer than that of the Non-NIPEC group (24.5 vs. 10.3 months, P = 0.005). Pathological type, preoperative thrombosis and postoperative NIPEC (HR = 0.423, 95%CI: 0.228-0.786, P = 0.006) were independent prognostic factors for CC 2-3 patients. CONCLUSIONS: For MPM patients receiving CRS + HIPEC, postoperative intraperitoneal combined with intravenous chemotherapy may improve the survival of CC 2-3 patients, but CC 0-1 patients do not seem to derive the same benefit.

Prescribing Trends and Associated Outcomes of Antiepileptic Drugs and Other Psychotropic Medications in US Nursing Homes: Proposal for a Mixed Methods Investigation.

BACKGROUND: Pilot data suggest that off-label, unmonitored antiepileptic drug prescribing for behavioral and psychological symptoms of dementia is increasing, replacing other psychotropic medications targeted by purposeful reduction efforts. This trend accelerated during the COVID-19 pandemic. Although adverse outcomes related to this trend remain unknown, preliminary results hint that harms may be increasing and concentrated in vulnerable populations. OBJECTIVE: Using a mixed methods approach including both a retrospective secondary data analysis and a national clinician survey, this study aims to describe appropriate and potentially inappropriate antiepileptic and other psychoactive drug prescribing in US nursing homes (NHs), characteristics and patient-oriented outcomes associated with this prescribing, and how these phenomena may be changing under the combined stressors of the COVID-19 pandemic and the pressure of reduction initiatives. METHODS: To accomplish the objective, resident-level, mixed-effects regression models and interrupted time-series analyses will draw on cohort elements linked at an individual level from the Centers for Medicare and Medicaid Services' (CMS) Minimum Data Set, Medicare Part D, Medicare Provider Analysis and Review, and Outpatient and Public Use Files. Quarterly cohorts of NH residents (2009-2021) will incorporate individual-level data, including demographics; health status; disease variables; psychotropic medication claims; comprehensive NH health outcomes; hospital and emergency department adverse events; and NH details, including staffing resources and COVID-19 statistics. To help explain and validate findings, we will conduct a national qualitative survey of NH prescribers regarding their knowledge and beliefs surrounding changing approaches to dementia care and associated outcomes. RESULTS: Funding was obtained in September 2022. Institutional review board exemption approval was obtained in January 2023. The CMS Data Use Agreement was submitted in May 2023 and signed in March 2024. Data access was obtained in June 2024. Cohort creation is anticipated by January 2025, with crosswalks finalized by July 2025. The first survey was fielded in October 2023 and published in July 2024. The second survey was fielded in March 2024. The results are in review as of July 2024. Iterative survey cycles will continue biannually until December 2026. Multidisciplinary dissemination of survey analysis results began in July 2023, and dissemination of secondary data findings is anticipated to begin January 2025. These processes are ongoing, with investigation to wrap up by June 2027. CONCLUSIONS: This study will detail appropriate and inappropriate antiepileptic drug use and related outcomes in NHs and describe disparities in long-stay subpopulations treated or not treated with psychotropics. It will delineate the impact of the pandemic in combination with national policies on dementia management and outcomes. We believe this mixed methods approach, including processes that link multiple CMS data sets at an individual level and survey-relevant stakeholders, can be replicated and applied to evaluate a variety of patient-oriented questions in diverse clinical populations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64446.

Prevalence and disparities in sexual and reproductive health of women of reproductive age (20-49 years) in China: A national cross-sectional study.

Background: Ensuring women's sexual and reproductive health (SRH) is a fundamental human right and key to 2030 agenda of the UN Sustainable Development Goals (SDGs), yet limited evidence exists on SRH in China, including national estimates and disparities of women's SRH experiences, gynaecological diseases, and sexually transmitted diseases (STDs). Methods: A national cross-sectional survey based on a multistage stratified sampling from 15 provinces of China was performed from May 2019 to April 2021. A total of 12 815 reproductive-aged (20-49 years) women were involved. The SRH experiences (including age at menarche, age at first sexual activity, history of abortion, miscarriage, recurrent miscarriage, stillbirth, age at first delivery, types of delivery), the history of gynaecological diseases and STDs, as well as the environmental factors of participants were investigated. Human development index (HDI) was utilised to categorise and describe the socioeconomic status of the regions. The prevalence rates of diseases were compared among different HDI regions. Results: We observed a decrease in the mean age at menarche, an increase in the proportion of women who became sexually active before 20, and a modest rise in mean age at first childbirth across generations. Age-standardised prevalence estimates of miscarriage, recurrent miscarriage, artificial abortion, ectopic pregnancy, and stillbirth were 9.3, 1.4, 55.7, 3.3, and 2.1%, respectively. Approximately 50% of participants reported a history of gynaecological diseases, with vulvovaginitis, cervicitis, and pelvic infection diseases being the most prevalent. The overall prevalence of STDs was estimated at 22.2‰, with mycoplasma genitalium infection having the highest reported prevalence. Disease prevalence varies across HDI regions. Conclusions: Women's SRH behaviours and experiences have evolved, along with shifts in the spectrums of gynaecological diseases and STDs in China. Urgent recalibration of health care policies and disease control strategies is necessary, aligning them with women's changing SRH needs, ultimately ensuring their reproductive health and rights.

Exploring how starting work during COVID-19 impacted post-foundation career decisions of new doctors: a mixed methods study.

OBJECTIVES: This study addressed two research questions: What factors do doctors in training describe as influencing their choices to apply (or not apply) for specialty training during their Foundation Year 2? Which of these factors are specific to the context of the COVID-19 pandemic, and the unique experiences of the cohort of doctors who qualified early during the pandemic? DESIGN: Sequential explanatory mixed methods study: Quantitative survey. Qualitative semistructured interviews. Quantitative data were analysed with logistic regression. Qualitative data were analysed using reflexive thematic analysis. SETTING: UK-wide. PARTICIPANTS: Junior doctors who graduated medical school in 2020. SURVEY: 320 participants (22% of those contacted). 68% (n=219) were female, 60% (n=192) under 25 and 35% (n=112) 25-30. 72% (n=230) were white, 18% (n=58) Asian and 3% (n=10) black. Interviews: 20 participants, 10 had applied for specialty training, 10 had not. RESULTS: A minority of respondents had applied for specialty training to start in 2022 (114, 36%). While burnout varied, with 15% indicating high burnout, this was not associated with the decision to apply. This decision was predicted by having taken time off due to work-related stress. Those who had not taken time off were 2.4 times more likely to have applied for specialty training (OR=2.43, 95% CI 1.20 to 5.34). Interviews found reasons for not applying included wanting to 'step off the treadmill' of training; perceptions of training pathways as inflexible, impacting well-being; and disillusionment with the community and vocation of healthcare, based, in part, on their experiences working through COVID-19. CONCLUSIONS: Participants infrequently cited factors specific to the pandemic had impacted their decision-making but spoke more broadly about challenges associated with increasing pressure on the health service and an eroded sense of vocation and community.

Enhanced production of health-promoting phenolic compounds using a novel endophytic fungus Talaromyces neorugulosus R-209 isolated from pigeon pea in a natural habitat by l-phenylalanine feeding.

In this study, nine endophytic fungi capable of producing multiple phenolic compounds were screened and identified from 152 fungi isolated from pigeon pea in a natural habitat (Honghe, Yunnan Province, China). Talaromyces neorugulosus R-209 exhibited the highest potential for phenolic compound production. L-phenylalanine feeding was used to enhance phenolic compound production in T. neorugulosus R-209 cultures. Under the optimal feeding conditions (l-phenylalanine dose of 0.16 g/L and feeding phase of 6 days), the yields of genistein, apigenin, biochanin A, and cajaninstilbene acid increased by 15.59-fold, 7.20-fold, 25.93-fold, and 10.30-fold over control, respectively. T. neorugulosus R-209 fed with l-phenylalanine was found to be stable in the production of phenolic compounds during ten successive subcultures. Moreover, bioactivities of extracts of T. neorugulosus R-209 cultures were significantly increased by l-phenylalanine feeding. Overall, l-phenylalanine feeding strategy made T. neorugulosus R-209 more attractive as a promising alternative source for the production of health-beneficial phenolic compounds in the nutraceutical/medicinal industries.

Dietary supplementation with calcitriol or quercetin improved eggshell and bone quality by modulating calcium metabolism.

This study was aimed to investigate the effects of dietary calcitriol or quercetin supplementation on eggshell and bone quality of laying hens. In trial 1, 72 Hy-Line Brown layers (80-week-old) with weak-shelled strength (25 to 30 N) were assigned into 4 dietary treatments with 6 replicates of 3 birds and fed a basal diet (4% calcium level) or basal diets supplemented with 0.5% calcium, 5 µg/kg calcitriol or 500 mg/kg quercetin for 4 weeks. In trial 2, 360 Hy-Line Brown layers (60-week-old) were divided into 3 groups with 8 replicates of 15 birds: control group (basal diet), calcitriol group (basal diet + 5 µg/kg calcitriol), and quercetin group (basal diet + 500 mg/kg quercetin). This trial lasted for 12 weeks. The results showed that dietary calcitriol or quercetin improved eggshell quality in both trials (P < 0.05). In trial 2, compared with the control group, both calcitriol and quercetin supplementations improved femoral bone quality, calcium retention of hens and calcium content in uterine fluid at 18.5 h post-oviposition (PO) (P < 0.05), along with enhancing uterine morphology. Compared to the control group, supplemental calcitriol or quercetin up-regulated the relative mRNA expression levels of uterine transient receptor potential cation channel, subfamily V, member 6 (TRPV6) at 8.5 h PO and plasma membrane calcium-ATPase (PMCA), vitamin D receptor (VDR), estrogen receptor alpha (ERα) at 18.5 h PO (P < 0.05), but down-regulated the uterine caspase 3 (CASP3) relative mRNA expression level at 8.5 h PO (P < 0.05). Meanwhile, the femoral relative mRNA expression levels of tartrate-resistant acid phosphatase (TRAP) (up-regulated at 8.5 and 18.5 h PO) and alkaline phosphatase (ALP) (up-regulated at 8.5 h PO but down-regulated at 18.5 h PO) were also affected by calcitriol or quercetin supplementation (P < 0.05). Compared to the calcitriol, quercetin increased hen-day egg production and femoral medullary bone volume/bone tissue volume but reduced femoral stiffness (P < 0.05), which were accompanied by increased relative mRNA expression levels of uterine TRPV6, estrogen receptor beta (ERß) at 18.5 h PO (P < 0.05). Overall, both dietary calcitriol and quercetin could improve eggshell and bone quality by modulating calcium metabolism of aged layers. Compared to calcitriol, dietary quercetin up-regulated the expression of uterine calcium transporters, without affecting eggshell quality.

Short Chain Chlorinated Paraffins Impaired Spermatogenesis Process in Mice via Inhibiting α-KG/TET Enzyme Activity.

Short chain chlorinated paraffins (SCCPs) are widely found in various environmental media and potentially threaten human health. However, the toxicity mechanisms of SCCPs to the male reproductive system remain unclear. In this study, male BALB/c mice and GC-1 cells were used to investigate the reproductive toxicity of SCCPs and their molecular mechanisms. SCCPs decreased the content of the tricarboxylic acid cycle intermediate α-KG in testicular cells, thus inhibiting the activity of the DNA demethylase TET enzyme and resulting in an increase in the overall methylation level of the testicular genome. Correspondingly, the promoter demethylation and expression of spermatogenesis-related genes Rbm46, Sohlh1, Kit, and Dmrt1 were significantly reduced by SCCPs, which further prevented the transformation of spermatogonia to spermatocytes and reduced sperm quality in mice. The in vitro experiments suggested that the TGFß pathway activated by oxidative stress might be an essential reason for inhibiting the tricarboxylic acid cycle and the reduction of α-KG content in testicular cells induced by SCCPs. Overall, this study reveals a novel metabolic regulatory mechanism of SCCPs-induced spermatogenesis disorders, which provides an essential theoretical basis for the prevention of reproductive toxicity of SCCPs.

COL12A1 Promotes Osteosarcoma Progression via the FAK/PI3K/AKT/mTOR Pathway.

BACKGROUND: Osteosarcoma (OS) is a common malignancy among adolescents and children, characterized by a high propensity for metastasis and resistance to chemotherapy. AIMS: This study aimed to investigate the role of COL12A1, a gene often overexpressed in various cancers and associated with poor prognosis, in the progression of OS and explore the underlying mechanisms. METHODS: The expression pattern and potential function of COL12A1 in OS were evaluated using bioinformatics analyses, clinical sample examination, and OS cell lines. Various assays, including transwell, CCK-8, flow cytometry, and wound healing, were performed to assess the impact of COL12A1 on OS cell growth, cell cycle progression, apoptosis, invasion, and migration. Western blot analysis was conducted to investigate markers associated with the FAK/PI3K/AKT/mTOR pathway. RESULTS: COL12A1 expression was significantly elevated in OS tissues and cells. Upregulation of COL12A1 promoted cell growth, accelerated cell cycle progression, and enhanced migration and invasion while inhibiting apoptosis. Conversely, the knockdown of COL12A1 had the opposite effect. Additionally, COL12A1 overexpression increased the phosphorylation of components in the FAK/PI3K/AKT/mTOR pathway. The FAK inhibitor Y15 mitigated the effects of COL12A1 overexpression on cell apoptosis, invasion, proliferation, and the FAK/PI3K/AKT/mTOR pathway in OS. CONCLUSION: Our findings indicated that COL12A1 enhanced OS development by activating the FAK/PI3K/AKT/mTOR pathway, suggesting that COL12A1 could serve as a valuable biomarker for the prediction and identification of OS patients.

PLXDC1 serves as a potential prognostic marker and involves in malignant progression and macrophage polarization in colon cancer.

The malignant behavior and immune escape ability of cancer cells lead to therapeutic failure and poor prognosis for patients with various cancers, including colon cancer. Plexin domain containing 1 (PLXDC1) was initially identified to exert key roles in tumor by regulating angiogenesis and has recently proved to be involved in cell proliferation and migration of glioblastoma and gastric cancer cells. However, its roles in colon cancer remain unclear. In this study, the online bioinformatics databases confirmed high expression of PLXDC1 in colon cancer specimens, which was associated with cancer stages and nodal metastasis. Similarly, the increased expression of PLXDC1 was also validated in our collected samples and colon cancer cells. Moreover, patients with high expression of PLXDC1 had shorter survival, indicating that PLXDC1 might be a potential prognostic predictor for colon cancer patients. Notably, targeting PLXDC1 inhibited cancer cell viability and invasion, and enhanced cell apoptosis. Intriguingly, Tumor Immune Estimation Resource database confirmed that PLXDC1 expression was related to various tumor-infiltrating immune cells in colon adenocarcinoma including macrophages, and its expression was also correlated with M2-like macrophage markers. In vitro, colon cancer cells with PLXDC1 downregulation had a reduced ability to recruit and polarize macrophage towards M2 phenotype by decreasing the percentage of CD206+ cells and M2-like markers (CD206, CD163, arginase1, and interleukin 10 [IL-10]). Moreover, PLXDC1 knockdown attenuated M2 macrophage-mediated promotion in cancer cell viability and invasion. Mechanically, inhibition of PLXDC1 suppressed activation of the IL-6/Signal transducer and activator of transcription 3 (STAT3) signaling. Reactivating the above pathway by transfection with IL-6 plasmids reversed the suppressive effects of PLXDC1 knockdown on cancer cell malignant behaviors, macrophage recruitment and M2-like polarization. Thus, PLXDC1 downregulation may inhibit the malignancy of colon cancer cells and their ability to recruit and polarize macrophages towards M2 phenotype by blocking the IL-6/STAT3 pathway. Together, targeting PLXDC1 may attenuate the progression of colon cancer by direct roles in cancer cells and indirect roles in macrophage polarization, representing a promising therapeutic target for colon cancer patients.

Temporal and Spatial Variations in Zebrafish Hairy/E(spl) Gene Expression in Response to Mib1-Mediated Notch Signaling During Neurodevelopment.

Notch signaling is a conserved pathway crucial for nervous system development. Disruptions in this pathway are linked to neurodevelopmental disorders, neurodegenerative diseases, and brain tumors. Hairy/E(spl) (HES) genes, major downstream targets of Notch, are commonly used as markers for Notch activation. However, these genes can be activated, inhibited, or function independently of Notch signaling, and their response to Notch disruption varies across tissues and developmental stages. MIB1/Mib1 is an E3 ubiquitin ligase that enables Notch receptor activation by processing ligands like Delta and Serrate. We investigated Notch signaling disruption using the zebrafish Mib1 mutant line, mib1ta52b, focusing on changes in the expression of Hairy/E(spl) (her) genes. Our findings reveal significant variability in her gene expression across different neural cell types, regions, and developmental stages following Notch disruption. This variability questions the reliability of Hairy/E(spl) genes as universal markers for Notch activation, as their response is highly context-dependent. This study highlights the complex and context-specific nature of Notch signaling regulation. It underscores the need for a nuanced approach when using Hairy/E(spl) genes as markers for Notch activity. Additionally, it provides new insights into Mib1's role in Notch signaling, contributing to a better understanding of its involvement in Notch signaling-related disorders.

Reaction Time Induced a Two-Step Dissolution and Recrystallization Structural Transformation with Three Eu Metal-Organic Frameworks: Crystal Structures and Multiresponsive Fluorescence Detection.

Under solvothermal conditions, three 3D lanthanide metal-organic frameworks (Ln-MOFs): [Eu(H2DHTA)1.5(DMF)2]·DMF (1), [Eu(H2DHTA)0.5(DHTA)0.5(DMF)(H2O)]·2H2O (2), and Eu(HCOO)3 (3) (H4DHTA = 2,5-dihydroxyterephthalic acid) have been synthesized by different reaction times. Interestingly, induced by reaction time, compounds 1-3 underwent a two-step dissolution and recrystallization structural transformation (DRST) reaction. Investigations on the DRST processes were carried out, and the transformation pathway was deduced, which was verified by XRD analyses. Notably, compound 2 demonstrates pronounced luminescence as well as high stability in water and other organic solvents. The fluorescent detection of furan antibiotics can serve as turn-off effects, and glutamic acid (Glu), aspartic acid (Asp), and riboflavin (VB2) can serve as the turn-on effect. To explain the enhancing and quenching mechanisms, XRD, UV-visible absorption spectroscopy, electrochemistry, IR spectra, theoretical calculation, fluorescence lifetimes, and XPS were discussed. Additionally, MOF-coated test strips were utilized to detect these analytes, exhibiting excellent agreement with fluorescence spectroscopy. This work provides an example for more effective designs to employ Ln-MOFs as multiresponsive fluorescent sensors for detection of environmental pollutants in aqueous solution.

Full-Length Immune Repertoire Reconstruction and Profiling at the Transcriptome Level Using Long-Read Sequencing.

BACKGROUND: Due to the diversity of the immune repertoire (IR), reconstructing full-length IR using traditional short-read sequencing has proven challenging. METHODS: A full-length IR sequencing (FLIRseq) work flow was developed with linear rolling circle amplification and nanopore sequencing. Its accuracy and quantification ability were verified by plasmid mixtures and commercial B-cell receptor/T-cell receptor sequencing (BCR/TCR-seq) based on short reads. IRs in tissues and the peripheral blood from 8 patients with acute lymphoblastic leukemia, 3 patients with allergic diseases, 4 patients with psoriasis, and 5 patients with prostate cancer were analyzed using FLIRseq. RESULTS: FLIRseq reads had lower mismatch rates and gap rates, and higher identify rates than nanopore reads (all P < 2.2 × -16). The relative quantification of components by FLIRseq was consistent with the actual quantification (P > 0.05). FLIRseq had superiority over BCR/TCR-seq, providing the long complementarity-determining region 3, B-cell isotype, and the rarely used V gene sequence. FLIRseq observed an increase in clonotype diversity (P < 0.05) and a decrease in the percentage of abnormal BCRs/TCRs in patients with leukemia in remission. For patients with allergic diseases or psoriasis, FLIRseq provided direct insights into V(D)J recombination and specific immunoglobulin classes. Compared with that in prostate cancer tissues, the full-length V segment of the biased T-cell receptor ß chain from lymphocytes in psoriatic tissues showed a more consistent AlphaFold2-predicted protein structure (P < 0.05). CONCLUSIONS: FLIRseq enables unbiased and comprehensive analyses of direct V(D)J recombination and immunoglobulin classes, thereby contributing to characterizing pathogenic mechanisms, monitoring minimal residual disease, and customizing adoptive cell therapy.

Meeting social welfare legal needs in end-of-life care: co-creation of a system-wide research partnership.

Background: Social welfare legal needs (matters of daily life, such as finances, housing and employment with legal rights, entitlements or protections) are prevalent towards end of life, creating significant difficulties for both patients and carers. Most people do not know where to go, although a range of services provide advice and support for addressing social welfare legal problems. Navigating this complex and fragmented system across health, social care and social welfare legal support is very challenging. Healthcare professionals are often the first contact for social welfare legal needs, although these are often overlooked and their impact on health and well-being unrecognised. Interprofessional learning can increase awareness of social welfare legal needs and build connections between service providers, offering a more holistic and cohesive multiagency response to the complex needs around end of life. The aim of the research was to co-create a robust foundation for cross-agency research investigating the impact of interprofessional learning on social welfare legal needs towards end of life in the North East England region. Objectives: Convene a research partnership group across academics, multiagency service providers and members of the public with lived experience. Consider and agree key issues for successful place-based multiagency research in this area. Co-create a complexity-appropriate research proposal with interprofessional learning as an intervention. Methods: A series of research activities was implemented to convene a multiagency partnership group and consider the key issues for successful place-based multiagency research. Data were collected from two online workshops, an optional reflective workbook, and a modified Delphi technique. Initial participants were selectively recruited from our established stakeholder and patient and public involvement groups. Increasing diversity of the partnership continued throughout the project, using contacts provided by group members. Representation of services supporting underserved groups was a priority. Results: All invited participants were recruited to the partnership, although contribution to research activities was variable. The partnership bridged knowledge gaps between services and united diverse perspectives, expertise and experience. A greater understanding of the barriers and opportunities for place-based multiagency working was generated, such as considering the importance of language in facilitating collaboration and responding to concerns around capacity. A non-hierarchical partnership was meaningful, with both personal and professional insights viewed as equally important. Facilitators to engagement with interprofessional learning were identified including the need for leadership endorsement. A non-traditional, mixed-method approach to interprofessional learning evaluation was favoured, with both qualitative and quantitative measures at three levels: patient and carer, professional learners and organisations. Important outcomes included raising awareness, connectedness and space to reflect. Limitations: The partnership group expanded throughout the course of the project. While this extended diversity, variable participation hindered depth of discussion, with participants engaging at different points and with different understanding levels of the project. Supplementary materials provided some mitigation. Capacity and funding constraints limited engagement for some participants. Conclusions: Convening a multiagency partnership generated insights into the benefits, barriers and facilitators to research co-design and potential measures of success of interprofessional learning. Future work: Learning from this project has informed a complexity-appropriate research proposal to evaluate the impact of interprofessional learning as an intervention across different stakeholders. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR135276.

Social welfare legal issues, such as unsuitable housing, job difficulties and money concerns, are common in the last 12 months of a person's life and they affect carers too. Getting the right help can be difficult as it is hard to know where to go. Organisations and services often work separately from each other. Healthcare professionals are often the first contact for social welfare legal needs, but they may not be able to provide the required support. Interprofessional learning brings professionals together to learn from each other and connect services better. We think this will make it easier for people to get the help they need when the same is required. We set up a group of professionals and four people with personal experience. This partnership group started with people and organisations we knew already but more joined during the project. By the end, 37 different services, representing a range of health, advice and community services, had joined the research group. All services had experience of social welfare legal issues in the last 12 months of life. The group discussed running research together and how interprofessional learning could be tested in our next research project. Research activities were: two online meetings to discuss key questions a workbook which gave time to think about the questions we were asking a survey which asked participants their views about measuring success of interprofessional learning. Group members brought a variety of experiences and opinions. Some had difficulty taking part, mainly because of time. We learnt that professional and personal experiences are as important as each other and that it is important to avoid jargon. Testing if interprofessional learning makes a difference needs to look at people using services, professionals and organisations. We have written a funding application, based on what we have learnt in this project.

Three patients with new mutations in the EPCAM variant gene for congenital tufting enteropathy and a mutation review in China: a case report.

Background: Congenital tufting enteropathy (CTE) is a rare cause of intractable congenital diarrhea in children, always resulting in parenteral nutrition (PN) dependency. We aimed to report novel mutations in Chinese patients and to illustrate the clinical, histopathological, and molecular features of CTE in China. Case Description: We report three cases of CTE diagnosed with whole-exome sequencing (WES) and MOC31 [a monoclonal antibody of epithelial cell adhesion molecule (EPCAM)] immunohistochemistry. The main manifestations in the three patients were watery diarrhea and growth retardation. Upper endoscopy in three patients revealed villous atrophy of the duodenal mucosa. Histological examination revealed villus abnormalities and two patients with focal tufting. All of the three patients revealed a complete absence of EPCAM expression through MOC31 immunohistochemistry. Five novel mutations, including c.319delG, c.505_507delGAG, c.491+1G>C, c.60del (p.F20Lfs*17), and c.353G>A, in EPCAM were identified through molecular analysis. In our review, there were 18 different mutations in 11 patients from nine studies, with 12 mutations reported only once. In China, 73% of the patients were compound heterozygotes, and most of the pathogenic variants were in exon 3. All patients presented with congenital diarrhea and needed PN because of growth retardation, even when diarrhea was improved. Of the 11 patients, 3 (27%) died. Conclusions: CTE is rare and fatal, and lacks characteristic changes during endoscopy. Patients with CTE require early diagnosis via histological examination and genetic detection to improve survival.

[Risk Factors and a Prediction Model for Frequent Acute Exacerbations of Chronic Obstructive Pulmonary Disease].

Objective To identify the risk factors of patients with frequent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and construct a prediction model based on the clinical data,providing a theoretical basis for the clinical prevention and treatment. Methods A total of 25 638 COPD patients admitted to the Department of Respiratory and Critical Care Medicine,the Third People's Hospital of Chengdu from January 1,2013 to May 1,2023 were selected.Among them,11 315 patients were included according to the inclusion and exclusion criteria,and their clinical characteristics were analyzed.Multivariate Logistic regression was carried out to identify the risk factors for frequent AECOPD.A nomogram model was utilized to quantify the risk of acute exacerbation,and the performance of the prediction model was assessed based on the area under the receiver operating characteristic (ROC) curve. Results In the patients with frequent AECOPD,male percentage (P<0.001),age (P<0.001),urban residence (P<0.001),smoking (P<0.001),length of stay (P<0.001),total cost (P<0.001),antibiotic cost (P<0.001),diabetes (P=0.003),respiratory failure (P<0.001),heart disease (P<0.001),application of systemic glucocorticoids (P<0.001),white blood cell count (P<0.001),neutrophil percentage (P<0.001),C-reactive protein (P<0.001),total cholesterol (P<0.001),and brain natriuretic peptide (BNP) (P<0.001) were all higher than those in the patients with infrequent AECOPD.Multivariate Logistic regression analysis revealed that age,urban residence,smoking,diabetes,heart disease,Pseudomonas aeruginosa infection,application of systemic glucocorticoids,antibiotics,respiratory failure,and elevated white blood cell count,total cholesterol,and BNP were independent risk factors for hospitalization due to frequent AECOPD.A nomogram model of hospitalization due to frequent AECOPD was constructed according to risk factors.The ROC curve was established to evaluate the performance of the model,which showed the area under the ROC curve of 0.899 (95%CI=0.892-0.905),the sensitivity of 85.30%,and the specificity of 79.80%. Conclusion Frequent AECOPD is associated with smoking,heart disease,application of systemic glucocorticoids,Pseudomonas aeruginosa infection,age,low body mass index,and elevated BNP.Predicting the risks of hospitalization due to frequent AECOPD by the established model can provide theoretical support for the treatment and risk factor management of the patients.

Ultra-Strong Protein-Based Hydrogels via Promoting Intermolecular Entanglement of the Amorphous Region.

Proteins are classified as biopolymers which share similar structural features with semi-crystalline polymers. Although their unique biocompatibility facilitates the universal applications of protein-based hydrogels in the biomedical field, the mechanical performances of protein-based hydrogels fall short of practical requirements. Conventional strategies for enhancing mechanical properties focus on forming regularly folded secondary structures as analogs of crystalline regions. This concept is based on proteins as the analogy of semi-crystalline polymers, in which crystalline regions profoundly contribute to the mechanical performances. Even though the contribution of the amorphous region is equally weighted for semi-crystalline polymers, their capacity to improve the mechanical performances of protein-based structures is still undervalued. Herein, the potential of promoting the mechanical performances is explored by controlling the state of amorphous regions in protein-based hydrogels. A fibril protein is chosen, regenerated silk fibroin (RSF), as a model molecule for its similar viscoelasticity with a semi-crystalline polymer. The amorphous regions in the RSF hydrogels are transformed from extended to entangled states through a double-crosslinking method. The formation of entanglement integrates new physically crosslinked points for remarkable improvement in mechanical performances. A robust hydrogel is not only developed but also intended to provide new insights into the structural-property relationship of protein-based hydrogels.