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Literary discussions are widely utilized in education, yet their profound impact on students' comprehension requires in-depth exploration. This paper delves into the influence of literary discussions on student comprehension and examines how these discussions can enhance students' understanding and analytical skills. Through literature reviews and case analyses, this study investigates teaching strategies, student engagement levels, classroom ambiance, and other factors involved in literary discussions, revealing the potential mechanisms through which literary discussions influence student comprehension. The paper explores variations in the application of literary discussions across different types of literary works (novels, poetry, drama, etc.) and their relationship with students' creative thinking. Finally, the paper provides recommendations to assist educators in effectively utilizing literary discussions to enhance students' comprehension skills. Students must have the opportunity to discuss literature in ways that provoke deep thought and meaning from each work they encounter. Therefore, English Language Arts teachers and instructors must be creative in finding unique ways in which they encourage their students to experience and respond to literature. This paper discusses a variety of strategies to implement in virtual and in-person classrooms, such as Socratic seminar, Teacher-led as a facilitator, Teacher-led as a promoter of diverse perspectives, Using student-generated discussion questions whole class, Using student-generated discussion questions in small groups, Using Close-ended questions, Using Open-ended questions, Inquiry-based, Making real-world connections to the literature, Literature Circles. These literary discussion strategies can be used for both fiction and nonfiction literature.

Autistic adults experience high rates of unemployment, yet research investigating what predicts employment success produces inconsistent results. By utilising longitudinal person-oriented analyses, this study aimed to identify employment trajectories of autistic adults to better understand what may predict stable autistic employment. Participants were 2449 autistic adults (1077 men, 1352 women, 20 non-binary, M = 42.25 years, SD = 14.24), recruited via the Netherlands Autism Register. Latent class analysis utilising employment status across eight annual waves was used to identify longitudinal employment profiles. Fit indices and the interpretability of results indicated a four-class model best fit the data, with profiles reflecting stable unemployment (n = 1189), stable employment (n = 801), early unemployment increasing in probability of employment (n = 183) and high probability of employment reducing across time to low employment (n = 134). Multinominal analyses suggested that compared to the 'stable unemployment' group, membership in the 'stable employment' profile was predicted by fewer autistic traits, lower age, male gender, higher education and diagnosis age, and fewer co-occurring conditions. Higher education predicted both other profiles, with lower age and fewer co-occurring conditions predicting membership in the increasing employment class. Taken together, findings highlight the utility of person-oriented approaches in understanding the longitudinal challenges autistic adults experience maintaining employment and identifies key areas of support.

It is essential for modern medical students to continuously enhance their clinical thinking abilities. This study aims to evaluate the efficacy of the combined World Café discussion and case-based learning (CBL) approach within the clinical thinking training course. The clinical thinking training course incorporated the combined World Café discussion and CBL approach. The assessment of the accuracy and rationality of clinical symptoms, medical examination, pathological processes, diagnostic results, diagnostic basis, and drug use was conducted through case-related queries. Feedback from students and instructors regarding the teaching content, teaching process, and teaching effect was gathered through questionnaires. The findings indicate that the students achieved high marks in all assessed areas, including clinical symptoms, medical examination, pathological processes, diagnostic results, diagnostic basis, and drug use. The feedback from students and instructors on the teaching content, teaching process, and teaching effect was positive. Medical educators can use our findings to implement the combined World Café discussion and CBL mode to enhance student engagement.

Abstract Clinical evidence supports the notion that T cell exhaustion and terminal differentiation pose challenges to the persistence and effectiveness of chimeric antigen receptor-T (CAR-T) cells. MEK1/2 inhibitors (MEKIs), widely used in cancer treatment due to their ability to inhibit aberrant MAPK signaling, have shown potential synergistic effects when combined with immunotherapy. However, the impact and mechanisms of MEKIs on CAR-T cells remain uncertain and controversial. To address this, we conducted a comprehensive investigation to determine whether MEKIs enhance or impair the efficacy of CAR-T cells. Our findings revealed that MEKIs attenuated CAR-T cell exhaustion and terminal differentiation induced by tonic signaling and antigen stimulation, thereby improving CAR-T cell efficacy against hematological and solid tumors. Remarkably, these effects were independent of the specific scFvs and costimulatory domains utilized in CARs. Mechanistically, analysis of bulk and single-cell transcriptional profiles demonstrates that the effect of MEK inhibition was related to diminish anabolic metabolism and downregulation of c-Fos and JunB. Additionally, the overexpression of c-Fos or JunB in CAR-T cells counteracted the effects of MEK inhibition. Furthermore, our Cut-and-Tag assay revealed that MEK inhibition downregulated the JunB-driven gene profiles associated with exhaustion, differentiation, anergy, glycolysis, and apoptosis. In summary, our research unveil the critical role of the MAPK-c-Fos-JunB axis in driving CAR-T cell exhaustion and terminal differentiation. These mechanistic insights significantly broaden the potential application of MEKIs to enhance the effectiveness of CAR-T therapy.

In order to accurately simulate the large-scale migration of plutonium in groundwater(a three-phase system), it is necessary to understand the interaction mechanisms between plutonium(Ⅳ), natural colloid, and granite(immobile media). The experimental results show that plutonium pseudo-colloids(i.e., Pu(Ⅳ) sorbed on the surfaces of soil colloids) have the strong mobility(i.e., the recovery percentage of plutonium after plutonium pseudo-colloids transported through columns filled with pore media, R). The mobility R increases with soil colloid concentration ρ(0≤ρ≤375.4 mg/L, 1.3%≤R≤52.5%). The master complexation speciation of Pu(Ⅳ) on the surfaces of soil colloids is \begin{document}$\equiv {\text{SOPu}} $\end{document}(OH)3. The speciation percentage(＞95%) is positively correlated with the colloid concentration. The results of experiments and surface complexation calculations confirm that plutonium pseudo-colloids enhance the mobility of Pu(Ⅳ) and thus pose a greater risk of contaminating far-field waters than the dissolved Pu(Ⅳ). The calculations of DLVO interaction potential indicate that the trough depth of the second energy minima(Фmin2) between colloids and media deepens with increasing colloid concentrations. This attractive interaction potential results in an increase in the adsorptive deposition efficiency of plutonium pseudo-colloids on the media surfaces. The DLVO calculations are consistent with the observation: the mobility of plutonium pseudo-colloids become weak(375.4 mg/L＜ρ≤2017.8 mg/L, 52.5%＜R≤12.7%).

Abstract Type 1 diabetes (T1D) is a chronic autoimmune condition characterized by hyperglycemia resulting from the destruction of insulin-producing β-cells that is traditionally deemed irreversible, but partial remission (PR) with temporary reversal of hyperglycemia is sometimes observed. Here we use single-cell RNA sequencing to delineate the immune cell landscape across patients in different T1D stages. Together with cohort validation and functional assays, we observe dynamic changes in TIGIT+CCR7− Tregs and CD226+CCR7−CD8+ cytotoxic T cells during the peri-remission phase. Machine learning algorithms further identify TIGIT+CCR7− Tregs and CD226+CD8+ T cells as biomarkers for β-cell function decline in a predictive model, while cell communication analysis and in vitro assays suggest that TIGIT+CCR7− Tregs may inhibit CD226+CCR7−CD8+ T cells via TGF-β signaling. Lastly, in both cyclophosphamide-induced and streptozotocin (STZ)-induced mouse diabetes models, CD226 inhibition postpones insulitis onset and reduces hyperglycemia severity. Our results thus identify two interrelated immune cell subsets that may serve as biomarkers for monitoring disease progression and targets for therapeutic intervention of T1D.

Abstract Purpose The essence of this scholarly work was to carefully outline the key factors intensifying the virulence and protracted contagion of COVID-19, particularly among individuals afflicted with hematologic malignancies (HM), in an epoch predominantly governed by the Omicron variant. Methods Adults with HM diagnosed with COVID-19 from November 2022 to February 2023 were monitored in this retrospective study. Patient blood samples yielded biochemical data, and COVID-19 was confirmed through RNA or antigen testing. The factors affecting severity and infection duration were examined using both univariate and multivariate logistic regression analyses. For calculating the overall survival probabilities, the Kaplan–Meier product limit approach was employed. Results In the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Of the participants, 29.3% (39 patients) were classified as Severe/Critical, while the other 70.7% (94 patients) were categorized as Non-severe. A significant difference was observed in vaccination status: 61.7% of patients in the Non-severe group had received at least a two-dose vaccine regimen, whereas 61.5% of the Severe/Critical group had either minimal or only one dose of vaccination. The data analysis revealed that elevated C-reactive protein levels (≥ 100 mg/L) significantly raised the risk of severe/critical conditions in HM patients with COVID-19, as determined by advanced multivariate logistic regression. The odds ratio was 3.415 with a 95% confidence interval of 1.294–9.012 (p = 0.013). Patients who continued to have positive nucleic acid tests and ongoing symptoms beyond 30 days were categorized as having a persistent infection, whereas those who achieved infection control within this timeframe were categorized as having infection recovery. Of the HM cohort, 11 did not survive beyond 30 days after diagnosis. The results from a competing risk model revealed that increased interleukin-6 levels (HR: 2.626, 95% CI: 1.361–5.075; p = 0.004) was significantly associated with persistent infection. Conversely, receiving more than two vaccine doses (HR: 0.366, 95% CI: 0.158–0.846; p = 0.019), and having high IgG levels (≥ 1000 mg/dl) (HR: 0.364, 95% CI: 0.167–0.791; p = 0.011), were associated with infection recovery. There was a notable disparity in survival rates between patients with persistent infections and infection recovery, with those in the non-persistent group demonstrating superior survival outcomes (P

Abstract Astragalus membranaceus (AM) roots are a well-known homologous medicine and food in China. AM stems, which are discarded and not used effectively, also contain many active compounds and exhibit beneficial effects. It has the potential to be explored as antibiotic alternative. Fermentation combined with enzymatic hydrolysis (FEH) is an effective strategy for extracting polyphenol and improving the usage of AM stems. Therefore, in this study, the conditions of FEH and extraction for polyphenol in AM stems were screened. The antioxidant activity of extract from AM stems without and with FEH (AMSE and FAMSE) was evaluated. The metabolite profiles of phenolic acids and flavonoids in AMSE and FAMSE were characterized by ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC–ESI-MS/MS). The results showed that the highest polyphenol content from AM stems was obtained with cellulase and pectinase (1:1, 2000 U/g), moisture content 43%, fermentation temperature 30 °C, and fermentation time 7 days. Selected extraction conditions of polyphenol were ethanol concentration 50%, ultrasonic power 500 W, extraction temperature 35 °C, and extraction time 40 min. On this condition, compared with AMSE, the polyphenol and flavonoid contents in FAMSE were significantly higher. FAMSE exhibited stronger DPPH, hydroxyl radical scavenging rate and reducing power than AMSE. The relative content of 3-(4-hydroxyphenyl)-propionic acid, dihydroferulic acid, isoferulic acid, 4-hydroxybenzoic acid, 4-hydroxyphenyllactic acid, ferulic acid, vanillic acid, syringic acid, gentisic acid, sinapic acid, apigenin, tricin, acacetin, daidzein, genistein, formononetin, prunetin, pratensein, rhamnocitrin and galangin were significantly upregulated in FAMSE. Graphical Abstract

Abstract High-grade serous ovarian carcinoma (HGSOC) is one of the most lethal gynecological cancer. Genetic studies have revealed gene copy number alterations (CNAs) frequently occurred in HGSOC pathogenesis, however the function and mechanism of CNAs for microRNAs are still not fully understood. Here, we show the dependence on gene copy number amplification of MIR937 that enhances cell autophagy and dictates HGSOC proliferative activity. Data mining of TCGA database revealed MIR937 amplification is correlated with increased MIR937 expression and cell proliferation of HGSOC. Deletion of MIR937 in HGSOC cells led to impaired autophagy and retarded cell proliferation, and the extent for its inhibitory effects scaled with the degree of MIR937 copy loss. Rescue assay confirmed miR-937-5p, a mature product of MIR937, was sufficient to restore its oncogenic function. Mechanistically, MIR937 amplification raised the expression of miR-937-5p, enhanced its binding to 3′ UTR of FBXO16 transcript, and thereby restricting FBXO16 degradative effects on ULK1. Our results demonstrate that MIR937 amplification augments cell autophagy and proliferation, and suggest an alternative strategy of MIR937/FBXO16/ULK1 targeting for HGSOC treatment.

To investigate the effects of a low-pressure electrostatic field combined with low temperature and high humidity on beef tenderness, this study utilized bovine longissimus dorsi muscle as the experimental material. The analysis included low-pressure electrostatic field thawing (at a temperature of 4 ℃ and relative humidity of 50%), low temperature and high humidity thawing (at a temperature of 4 ℃ and relative humidity of 98%), low-pressure electrostatic field combined with low temperature and high humidity thawing (temperature 4 ℃ and relative humidity 98%), and low temperature thawing (temperature 4 ℃ and relative humidity 50%). The parameters examined encompassed shear force, texture, water distribution, water content, water holding capacity, and sensory evaluation of frozen beef. The findings revealed that low-voltage electrostatic field combined with low-temperature and high-humidity thawing exhibited the shortest thawing time (804 min) compared to the other three thawing methods. The thawing loss (2.06%), cooking loss (26.09%), and centrifugation loss (15.00%) were significantly lower than the other three thawing methods (P

Abstract Background Quantifying the professional ethical challenges that nurses encounter is crucial for both theoretical insights and practical outcomes. The objective of this research is to assess the psychometric properties of the Chinese adaptation of the Moral Distress Scale for Healthcare Professionals (MD-APPS). Methods In 2024, a survey approach was utilized to engage with several tertiary-level healthcare institutions throughout China. A cohort of 448 nursing professionals who satisfied the specified selection benchmarks was consequently incorporated into the study. To evaluate the scale's reliability and validity, methods including the Content Validity Index (CVI), Factor Analysis—both Exploratory (EFA) and Confirmatory (CFA)—alongside assessments of internal consistency and test-retest reliability were employed. Results Expert evaluations yielded an I-CVI of 0.90, suggesting good content validity for the MD-APPS's Chinese adaptation. Exploratory Factor Analysis (EFA) revealed a bi-dimensional framework with 7 components, explaining 56.34% of the cumulative variance. Confirmatory Factor Analysis (CFA) outcomes displayed a χ-square/df ratio of 1.542. The estimate for Robust RMSEA was 0.054, and the SRMR was ascertained to be 0.041. Indices for both Robust TLI and Robust CFI surpassed the 0.9 threshold, indicating an acceptable fit; this aspect was supported by a P-value (Chi-square) of 0.094. The internal consistency, measured by Cronbach's α, was found to be 0.74, while the test-retest reliability over a two-week period reached 0.964. These findings provide initial evidence for the psychometric properties of the Chinese MD-APPS. Conclusion The Chinese adaptation of the MD-APPS demonstrates promising initial psychometric properties, suggesting its potential suitability for exploring nurses' professional ethical challenges within the Chinese cultural context. This scale may facilitate the identification of diverse elements influencing nurses' professional ethics and the assessment of the ethical climate in nursing practices. However, further validation studies are needed to fully establish its psychometric robustness across various healthcare settings in China.

To develop a new method for the sterilization of fresh-cut lettuce, plasma-activated water (PAW) combined with dielectric barrier discharge (DBD) plasma technology was applied in this study. Response surface methodological approach was performed to determine the optimal sterilization process parameters. Meanwhile, the microbial count, color, browning degree, firmness and weight loss rate were evaluated to investigate the effects of combined cold plasma treatments on the qualities of fresh-cut lettuce during the storage. Results showed that the total viable bacteria count on the surface of fresh-cut lettuce was (0.48±0.07) lg CFU/g under the optimal treatment conditions when PAW preparation time was 130 s, PAW soaking time was 5 min, and DBD plasma treatment time was 135 s. Moreover, during 7 days of storage, the combined cold plasma treatments could effectively inhibit the growth of microorganisms, maintain the color and firmness of fresh-cut lettuce, delay the increase of weight loss rate, and inhibit the occurrence of browning, which would effectively prolong the shelf life of fresh-cut lettuce.

Sodium-ion batteries are expected to gradually replace lithium-ion batteries in large-scale energy storage and two-wheeled electric vehicles because of their excellent low-temperature performance, cost advantages, and high safety. The development of sodium-ion battery anode materials with low cost, high reversible capacity, and excellent cycling stability is challenging for the industry. Because sodium ions are larger than lithium ions, graphite materials with long-range ordered structures suitable for lithium-ion battery anodes cannot be applied to sodium-ion batteries. Instead, the graphite domains of hard carbon materials are short and chaotically aligned, exhibiting a short-range ordered structure with local graphite zones inside the carbon layer. Moreover, the layer spacing of hard carbon is larger than that of graphite, which is conducive to the storage of sodium ions. Hard carbon is easily accessible and environmentally friendly, with a high carbon yield. Biomass-based hard carbon has attracted considerable attention because of its abundant raw material sources, low cost, easy accessibility, high carbon yield, environmental friendliness, and the presence of various elements. Its unique microstructure exhibits notable advantages and great commercial potential among several anode materials for sodium-ion batteries. The storage mechanism of sodium ions in hard carbon is controversial. Herein, we first analyze the adsorption behavior of sodium ions at the active sites on the hard carbon surface and the sequential process of their entry into the graphite scale layer. Moreover, we review four controversial sodium-ion storage mechanisms. Furthermore, we explore the storage mechanism of sodium ions in hard carbon and the differences between various biomass-based precursors. The content of each component and microstructure of different precursors vary, and several differences exist between nutshells, woody plants, and herbs. Their internal structural characteristics and different component contents play a key role in the performance of hard carbon. We enumerate the structural and component differences among various biomass-based precursors and summarize the distinctions in sodium-ion storage properties among different precursor hard carbons. To enhance the sodium storage performance of biomass-based hard carbon, an optimization strategy is proposed for sodium-ion battery anodes. This strategy involves manipulating the microstructure of the hard carbon anode, including adjusting the carbon layer spacing, pore structure, and specific surface area. In addition, the doping of elements, introduction of functional groups, and optimization of the electrolyte can improve the sodium storage performance of hard carbon. These insights can provide significant guidance for developing sodium-ion batteries.

Abstract Background The syncytiotrophoblast (SCT) layer in the placenta serves as a crucial physical barrier separating maternal-fetal circulation, facilitating essential signal and substance exchange between the mother and fetus. Any abnormalities in its formation or function can result in various maternal syndromes, such as preeclampsia. The transition of proliferative villous cytotrophoblasts (VCT) from the mitotic cell cycle to the G0 phase is a prerequisite for VCT differentiation and their fusion into SCT. The imprinting gene P57Kip2, specifically expressed in intermediate VCT capable of fusion, plays a pivotal role in driving this key event. Moreover, aberrant expression of P57Kip2 has been linked to pathological placental conditions and adverse fetal outcomes. Methods Validation of STK40 interaction with P57Kip2 using rigid molecular simulation docking and co-immunoprecipitation. STK40 expression was modulated by lentivirus in BeWo cells, and the effect of STK40 on trophoblast fusion was assessed by real-time quantitative PCR, western blot, immunofluorescence, and cell viability and proliferation assays. Co-immunoprecipitation, transcriptome sequencing, and western blot were used to determine the potential mechanisms by which STK40 regulates P57Kip2. Results In this study, STK40 has been identified as a novel interacting protein with P57Kip2, and its expression is down-regulated during the fusion process of trophoblast cells. Overexpressing STK40 inhibited cell fusion in BeWo cells while stimulating mitotic cell cycle activity. Further experiments indicated that this effect is attributed to its specific binding to the CDK-binding and the Cyclin-binding domains of P57Kip2, mediating the E3 ubiquitin ligase COP1-mediated ubiquitination and degradation of P57Kip2. Moreover, abnormally high expression of STK40 might significantly contribute to the occurrence of preeclampsia. Conclusions This study offers new insights into the role of STK40 in regulating the protein-level homeostasis of P57Kip2 during placental development.

Abstract Acute ischemic stroke (AIS) is a major global health concern due to its high mortality and disability rates. Hemorrhagic transformation, a common complication of AIS, leads to poor prognosis yet lacks effective treatments. Preclinical studies indicate that hyperbaric oxygen (HBO) treatment within 12 h of AIS onset alleviates ischemia/reperfusion injuries, including hemorrhagic transformation. However, clinical trials have yielded conflicting results, suggesting some underlying mechanisms remain unclear. In this study, we confirmed that HBO treatments beginning within 1 h post reperfusion significantly alleviated the haemorrhage and neurological deficits in hyperglycemic transient middle cerebral arterial occlusion (tMCAO) mice, partly due to the inhibition of the NLRP3 inflammasome-mediated pro-inflammatory response in microglia. Notably, reactive oxygen species (ROS) mediate the anti-inflammatory and protective effect of early HBO treatment, as edaravone and N-Acetyl-l-Cysteine (NAC), two commonly used antioxidants, reversed the suppressive effect of HBO treatment on NLRP3 inflammasome-mediated inflammation in microglia. Furthermore, NAC countered the protective effect of early HBO treatment in tMCAO mice with hyperglycemia. These findings support that early HBO treatment is a promising intervention for AIS, however, caution is warranted when combining antioxidants with HBO treatment. Further assessments are needed to clarify the role of antioxidants in HBO therapy for AIS.

Abstract The increasing amount of coal gasification fine slag (CGFS) necessitates its resource utilization. CGFS, mainly composed of porous carbonaceous particles and partially fused spherical or agglomerated ash particles, is an inexpensive and high-quality raw material for preparing adsorbent materials. However, the challenge remains in developing a simple, low-cost, and environmentally friendly method to produce high-performance porous materials from CGFS. In this study, a one-step treatment method using 2 mol/L nitric acid under hydrothermal conditions was proposed for CGFS. The adsorbent material (CGFS-2 M) prepared under a solid–liquid ratio of 2:5 and an initial concentration of 200 mg/L methylene blue (MB) exhibited an equilibrium adsorption capacity as high as 210.20 mg/g. The excellent adsorption performance of CGFS-2 M can be attributed to several factors: acid leaching for mineral removal and pore formation, resulting in a specific surface area and total pore volume 2.2 and 1.6 times that of untreated CGFS, respectively, and an optimized mesoporous pore size distribution favorable for MB adsorption; optimal mineral removal and a well-defined carbon microcrystal structure providing more space for MB adsorption; nitric acid treatment increasing the surface oxygen content and hydrophilicity, enhancing its ability to remove MB. The synergistic effect of pore structure improvement and surface modification indicates a feasible research direction for enhancing the performance of CGFS-based adsorbent materials. These results provide theoretical support for the development of efficient CGFS-based adsorbents.

In this paper, we investigated the potential use of a new organic-inorganic hybrid crystal structure based on KNO3 in ignition compositions. H2dabco[K(NO3)3] (DAN-2) with organic-inorganic hybrid crystal structure is synthesized through intermolecular assembly technology. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) were used to detect the crystal morphology, structure and molecular structure of DAN-2, which has a regular cubic structure. Experimental data were obtained using thermogravimetric/differential scanning calorimetry (TG-DSC), closed bomb test and high-speed photography, which were then used to study and analyze the thermal decomposition properties and combustion properties of DAN-2. The initial thermal decomposition temperature of DAN-2 was low (194 °C) and the activation energy of the thermal decomposition was 154 kJ/mol. Possible thermal decomposition mechanisms are further discussed and proposed. This research pushed forward the application of organic-inorganic hybrid crystal structure oxidant DAN-2 in ignition system.

Abstract Background A modified surgical technique of sutured scleral fixated intraocular lens (SSF-IOL) was applied in a patient with post-traumatic aniridia and aphakia. Case presentation A 51-year-old man was referred to our clinic with decreased vision (finger count) in his right eye. This patient had previously undergone primary repair of the ruptured globe and pars plana vitrectomy to manage ocular trauma in the same eye. On presentation, the best corrected visual acuity in his right eye was 20/40. The slit lamp examination of his right eye revealed loss of total iris and lens. Corneal endothelial cell density was 1462 cells/mm2. Fundoscopic examination of the right eye revealed a retinal attachment. For IOL implantation, a rigid poly methyl methacrylate IOL was used with a 2-point scleral fixation performed using a polypropylene suture. One year postoperatively, the uncorrected distance visual acuity was 20/32, and the manifest refraction was − 0.5/–1.5 × 130 (20/20). Pentacam revealed that the astigmatism of the anterior corneal surface and the total cornea was 1.1 D (axis: 59.8°) and 1.0 D (axis: 35.6°), respectively. The horizontal (3°–183°) cross-section image displayed an IOL with a 1° tilt and 0.425 mm decentration. The patient reported no dysphotopsia or photophobia and was satisfied with the visual results. OPD-scan III revealed that higher-order aberrations in the right eye were slightly higher than those in the left eye. No suture-related or other serious complications were observed. Conclusion The modified SSF-IOL technique can offer improved visual quality for patients with aniridia and aphakia by ensuring proper IOL positioning and reducing astigmatism.

Abstract Endometrial cancer (UCEC) is one of three major malignant tumors in women. The HOX gene regulates tumor development. However, the potential roles of HOX in the expression mechanism of multiple cell types and in the development and progression of tumor microenvironment (TME) cell infiltration in UCEC remain unknown. In this study, we utilized both the The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database to analyze transcriptome data of 529 patients with UCEC based on 39 HOX genes, combing clinical information, we discovered HOX gene were a pivotal factor in the development and progression of UCEC and in the formation of TME diversity and complexity. Here, a new scoring system was developed to quantify individual HOX patterns in UCEC. Our study found that patients in the low HOX score group had abundant anti-tumor immune cell infiltration, good tumor differentiation, and better prognoses. In contrast, a high HOX score was associated with blockade of immune checkpoints, which enhances the response to immunotherapy. The Real-Time quantitative PCR (RT-qPCR) and Immunohistochemistry (IHC) exhibited a higher expression of the HOX gene in the tumor patients. We revealed that the significant upregulation of the HOX gene in the epithelial cells can activate signaling pathway associated with tumour invasion and metastasis through single-cell RNA sequencing (scRNA-seq), such as nucleotide metabolic proce and so on. Finally, a risk prognostic model established by the positive relationship between HOX scores and cancer-associated fibroblasts (CAFs) can predict the prognosis of individual patients by scRNA-seq and transcriptome data sets. In sum, HOX gene may serve as a potential biomarker for the diagnosis and prediction of UCEC and to develop more effective therapeutic strategies.

Acute pancreatitis (AP) is a potentially fatal condition with no targeted treatment options. Although inhibiting xanthine oxidase (XO) in the treatment of AP has been studied in several experimental models and clinical trials, whether XO is a target of AP and what its the main mechanism of action is remains unclear. Here, we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP. We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models. We also found that allopurinol and febuxostat, as purine-like and non-purine XO inhibitors, respectively, exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points. Moreover, we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity. Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha (HIF-1α)-regulated lactate dehydrogenase A (LDHA) and NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathways and reduced the enrichment of 13C6-glucose to 13C3-lactate. Lastly, we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels, while pancreatic XO and urate were also increased in severe AP patients. These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.

Abstract Glycyrrhiza stems and leaves (GSL) are waste products of Glycyrrhiza; however, it has been considered a potential source of flavonoid compounds. In this study, GSL was processed by solid-state fermentation (SSF) to improve the flavonoid content and antioxidant activity. Firstly, a near-infrared (NIR) prediction model for flavonoid content in fermented Glycyrrhiza stems and leaves (FGSL) was established. Next, the effects of SSF on the antioxidant activity and metabolite profile of GSL were investigated. Finally, the possible mechanism of ferment release of flavonoids was explored based on enzyme activity, thermogravimetric analysis, and FTIR spectroscopy. The results revealed that NIR spectroscopy can efficiently analyze flavonoid contents in GSL, with predicted determination coefficient (Rp2) and root mean square error (RMSEP) of 0.9874 and 0.125, respectively. SSF significantly increased the levels of flavonoids, and enhanced the scavenging activities of DPPH radical and hydroxyl radical and reducing power of FGSL. Widely targeted metabolomic analysis showed the detection of 461 differential metabolites were identified after SSF, with 141 metabolites remarkably up-regulated and 320 metabolites of FGSL down-regulated during fermentation. The main types of differential metabolites were phenolic acids and flavonoids, and the destruction of cellulose by SFF was crucial to the release of flavonoids. In conclusion, our study revealed that SSF remarkably improved the phytochemical components of FGSL by increasing enzyme activity and destroying cellulose structure, thereby contributing to the enhancement of antioxidant activity. This study provided a scientific basis for the production of high-value flavonoids from plant materials and offered a novel approach to elucidate the release and conversion of flavonoids. Graphical Abstract

Statistics anxiety is a significant problem for students' learning experience in the psychological sciences. This article explores a novel teaching methodological approach during the global pandemic to improve students' performance by reducing their statistics anxiety. The subject design and teaching methodological approach were developed based on twenty years of experience taking into consideration the student feedback, while its implementation was aligned with the 5-E's Victorian Teaching and Learning pedagogical Model (VTLM). Moreover, to reduce the statistics anxiety, two sections were embedded in the Learning Management System of the subject: (1) an interactive web-based mindfulness intervention and (2) a head-start 'Ready, Set, Go' information pack. The implementation of these approaches resulted in a better understanding of statistical concepts and utilization of the SPSS software by the majority of the students (80% pass-rate). Consequently, a 6% increase in pass rates and an average of 32% increase in satisfaction scores for each item in the university central survey were observed. While the uniqueness of the first year of COVID-period makes comparisons difficult, it is matched by the urgency of the need for effective interventions to support student success.

Abstract Diabetes accelerates vascular senescence, which is the basis for atherosclerosis and stiffness. The activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and oxidative stress are closely associated with the deteriorative senescence in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). For decades, Sodium Tanshinone IIA Sulfonate (STS) has been utilized as a cardiovascular medicine with acknowledged anti-inflammatory and anti-oxidative properties. Nevertheless, the impact of STS on vascular senescence remains unexplored in diabetes. Diabetic mice, primary ECs and VSMCs were transfected with the NLRP3 overexpression/knockout plasmid, the tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) overexpression/knockout plasmid, and treated with STS to detect senescence-associated markers. In diabetic mice, STS treatment maintained catalase (CAT) level and vascular relaxation, reduced hydrogen peroxide probe (ROSgreen) fluorescence, p21 immunofluorescence, Senescence β-Galactosidase Staining (SA-β-gal) staining area, and collagen deposition in aortas. Mechanistically, STS inhibited NLRP3 phosphorylation (serine 194), NLRP3 dimer formation, NLRP3 expression, and NLRP3-PYCARD (ASC) colocalization. It also suppressed the phosphorylation of IkappaB alpha (IκBα) and NFκB, preserved A20 and CAT levels, reduced ROSgreen density, and decreased the expression of p21 and SA-β-gal staining in ECs and VSMCs under HG culture. Our findings indicate that STS mitigates vascular senescence by modulating the A20-NFκB-NLRP3 inflammasome-CAT pathway in hyperglycemia conditions, offering novel insights into NLRP3 inflammasome activation and ECs and VSMCs senescence under HG culture. This study highlights the potential mechanism of STS in alleviating senescence in diabetic blood vessels, and provides essential evidence for its future clinical application.

Abstract Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I–III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p

Abstract Depressive symptoms occur commonly in Alzheimer’s disease (AD). Although abnormalities in the amygdala-frontal circuit have been linked to emotional dysregulation and cognitive impairment, the neurological basis underlying these associations in AD patients with depressive symptoms (ADD) is unclear. We aimed to investigate the relationship between the amygdala-frontal circuit and depressive symptoms and cognitive function in ADD. We recruited 60 ADD, 60 AD patients without depressive symptoms (ADND), and 60 healthy controls (HC). Functional connectivity (FC) maps of the bilateral amygdala were compared. Fractional anisotropy (FA) of the amygdala-frontal circuit connected by the uncinate fasciculus (UF) was calculated using automated fiber quantification (AFQ). In addition, mediation analysis was performed to explore the effects of the amygdala-frontal circuit on the relationship between depressive symptoms and cognitive function. We found decreased bilateral amygdala FC with the inferior frontal gyrus (IFG) in the ADD group compared to the ADND and HC groups. Moreover, FA in the left frontal UF (nodes 64–97) was significantly lower in the ADD group than ADND group. Notably, amygdala-based FC with IFG and the left frontal UF FA mediated the relationship between depressive symptoms and cognitive function in ADD, with mediating effects ranging between 15 and 18%. Our study is the first to demonstrate the mediating effect of functional and microstructural abnormalities in the amygdala-frontal circuit in ADD. The findings suggest that the amygdala-frontal circuit may underlie emotional dysregulation in ADD, providing potential targets for treatment strategies.

Abstract Intercropping systems have garnered attention as a sustainable agricultural approach for efficient land use, increased ecological diversity in farmland, and enhanced crop yields. This study examined the effect of intercropping on the kiwifruit rhizosphere to gain a deeper understanding of the relationships between cover plants and kiwifruit in this sustainable agricultural system. Soil physicochemical properties and bacterial communities were analyzed using the Kiwifruit-Agaricus blazei intercropping System. Moreover, a combined analysis of 16S rRNA gene sequencing and metabolomic sequencing was used to identify differential microbes and metabolites in the rhizosphere. Intercropping led to an increase in soil physicochemical and enzyme activity, as well as re-shaping the bacterial community and increasing microbial diversity. Proteobacteria, Bacteroidota, Myxococcota, and Patescibacteria were the most abundant and diverse phyla in the intercropping system. Expression analysis further revealed that the bacterial genera BIrii41, Acidibacter, and Altererythrobacter were significantly upregulated in the intercropping system. Moreover, 358 differential metabolites (DMs) were identified between the monocropping and intercropping cultivation patterns, with fatty acyls, carboxylic acids and derivatives, and organooxygen compounds being significantly upregulated in the intercropping system. The KEGG metabolic pathways further revealed considerable enrichment of DMs in ABC transporters, histidine metabolism, and pyrimidine metabolism. This study identified a significant correlation between 95 bacterial genera and 79 soil metabolites, and an interactive network was constructed to explore the relationships between these differential microbes and metabolites in the rhizosphere. This study demonstrated that Kiwifruit-Agaricus blazei intercropping can be an effective, labor-saving, economic, and sustainable practice for reshaping bacterial communities and promoting the accumulation and metabolism of beneficial microorganisms in the rhizosphere.

Carbon capture and storage (CCS) and geological energy storage are essential technologies for mitigating global warming and achieving China’s “dual carbon” goals. Carbon storage involves injecting carbon dioxide into suitable geological formations at depth of 800 meters or more for permanent isolation. Geological energy storage, on the other hand, involves compressing air or other gases using surplus electricity during off-peak hours and temporarily storing them in underground reservoirs. These gases are then released during peak hours for power generation. Both technologies share commonalities in reservoir selection, with aquifers, depleted oil and gas reservoirs, and salt caverns all serving as potential storage sites. Carbon storage demands long-term containment, while geological energy storage necessitates multiple cycles of storage and release, requiring careful consideration during site evaluation. CCS projects are rapidly increasing globally, evolving towards networked and clustered configurations. In China, CCS projects are primarily focused on CO2-enhanced oil recovery, with fewer dedicated storage projects. However, direct storage projects are projected to dominate in the future and are also transitioning towards clustered development. China possesses favorable geological conditions for carbon storage, with relatively accurate estimates for oil and gas reservoir storage potential. Nevertheless, significant uncertainties persist regarding the storage capacity of saline aquifers. Compressed air energy storage in salt caverns is currently the predominant type of geological energy storage projects. Germany, the USA, and China have a total of five operating compressed air salt cavern energy storage power plants. China has abundant salt cavern resources, albeit with complex geological conditions. Suitable construction sites are concentrated in the eastern regions, and numerous projects are already underway. Compared to salt caverns, porous formations such as aquifers and depleted oil and gas reservoirs are more widespread and offer higher storage potential. However, technical challenges related to multiphase flow and chemical reactions need to be addressed. However, current site selection, potential assessment, efficiency optimization, and monitoring technologies face considerable challenges in meeting the demands of large-scale practical applications. Traditional hydrogeological exploration methods prove inadequate for selecting suitable sites, highlighting the need for efficient monitoring and risk control techniques. Additionally, there is a lack of cost-effective and accurate continuous monitoring technologies specifically designed for pressure and stress changes in storage and caprock formations. The development of key equipment components, such as monitoring and power generation systems, with independent intellectual property rights remains limited. Moreover, our reservoir simulation software requires further advancements to effectively simulate complex reservoirs at large scales. It is crucial to prioritize research and development in resource exploration, site selection technologies, and engineering equipment for both carbon sequestration and geological energy storage. The establishment of diverse demonstration projects and facilities for various storage options such as saline aquifers, depleted oil/gas fields are needed in the future as well.

Abstract Background Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia. Methods In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation. Results Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression. Conclusions These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health.

Abstract Background The cold tolerance of rice is closely related to its production and geographic distribution. The identification of cold tolerance-related genes is of important significance for developing cold-tolerant rice. Dongxiang wild rice (Oryza rufipogon Griff.) (DXWR) is well-adapted to the cold climate of northernmost-latitude habitats ever found in the world, and is one of the most valuable rice germplasms for cold tolerance improvement. Results Transcriptome analysis revealed genes differentially expressed between Xieqingzao B (XB; a cold sensitive variety) and 19H19 (derived from an interspecific cross between DXWR and XB) in the room temperature (RT), low temperature (LT), and recovery treatments. The results demonstrated that chloroplast genes might be involved in the regulation of cold tolerance in rice. A high-resolution SNP genetic map was constructed using 120 BC5F2 lines derived from a cross between 19H19 and XB based on the genotyping-by-sequencing (GBS) technique. Two quantitative trait loci (QTLs) for cold tolerance at the early seedling stage (CTS), qCTS12 and qCTS8, were detected. Moreover, a total of 112 candidate genes associated with cold tolerance were identified based on bulked segregant analysis sequencing (BSA-seq). These candidate genes were divided into eight functional categories, and the expression trend of candidate genes related to ‘oxidation-reduction process’ and ‘response to stress’ differed between XB and 19H19 in the RT, LT and recovery treatments. Among these candidate genes, the expression level of LOC_Os12g18729 in 19H19 (related to ‘response to stress’) decreased in the LT treatment but restored and enhanced during the recovery treatment whereas the expression level of LOC_Os12g18729 in XB declined during recovery treatment. Additionally, XB contained a 42-bp deletion in the third exon of LOC_Os12g18729, and the genotype of BC5F2 individuals with a survival percentage (SP) lower than 15% was consistent with that of XB. Weighted gene coexpression network analysis (WGCNA) and modular regulatory network learning with per gene information (MERLIN) algorithm revealed a gene interaction/coexpression network regulating cold tolerance in rice. In the network, differentially expressed genes (DEGs) related to ‘oxidation-reduction process’, ‘response to stress’ and ‘protein phosphorylation’ interacted with LOC_Os12g18729. Moreover, the knockout mutant of LOC_Os12g18729 decreased cold tolerance in early rice seedling stage signifcantly compared with that of wild type. Conclusions In general, study of the genetic basis of cold tolerance of rice is important for the development of cold-tolerant rice varieties. In the present study, QTL mapping, BSA-seq and RNA-seq were integrated to identify two CTS QTLs qCTS8 and qCTS12. Furthermore, qRT-PCR, genotype sequencing and knockout analysis indicated that LOC_Os12g18729 could be the candidate gene of qCTS12. These results are expected to further exploration of the genetic mechanism of CTS in rice and improve cold tolerance of cultivated rice by introducing the cold tolerant genes from DXWR through marker-assisted selection.

Abstract Background Neutrophils play an essential role in Alzheimer’s disease (AD) pathology. However, the extent of their heterogeneity remains poorly explored, particularly in the context of developing novel therapies targeting these cells. Results We investigate the population structure of neutrophils purified from peripheral blood samples of AD mice. Utilizing single cell RNA sequencing, we comprehensively map neutrophil populations into six distinct clusters and find that the Neu-5 subset is specially enriched in AD mice. This subset exhibits fewer specific granules and a lower mature score. Gene ontology (GO) analysis reveals that genes involved in cytokine-mediated signaling are downregulated in the Neu-5 cluster. Furthermore, we identify the Ccrl2 gene is specifically upregulated in this subgroup, which is confirmed by flow cytometry in AD mice. Finally, immunohistochemical staining indicates that CCRL2 protein is increased in the brains of AD mice. Conclusions We identify a unique CCRL2 positive neutrophil cluster, that is specifically enriched in the peripheral blood of AD mice.

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Its pathogenesis is not fully understood, and early diagnosis is challenging owing to the lack of effective biomarkers. This study aimed to analyze different samples to identify potential biomarkers and therapeutic targets. Methods Microarray datasets of RA, osteoarthritis (OA), and healthy control (HC) were downloaded from the Gene Expression Omnibus database. R software was used to identify differentially expressed genes (DEGs), which were visualized using volcano and heat maps. Venn diagrams, principal component analysis, gene set enrichment analysis, gene ontology, and Kyoto Encyclopedia of genes and genomes were used to analyze the data. A protein–protein interaction network was constructed, and synovial tissues from patients with RA and OA were collected for verification using the collagen‐induced arthritis mouse model. Results More DEGs were found in synovial tissues than in peripheral blood mononuclear cells or fibroblast‐like synoviocytes. Principal component analysis revealed significant differences between the RA and OA samples, highlighting the unique advantages of synovial tissue. Enrichment analysis revealed that metabolic and cytokine signaling pathways play crucial roles in the development of RA. Further analysis of the four synovial datasets identified 54 DEGs, of which signaling lymphocytic activation molecule family (SLAMF) 8 was identified as the key molecule. SLAMF8 levels were increased in the synovial tissue of patients with RA compared to those of patients with OA (0.38 ± 0.19 vs. 12.40 ± 1.66), and SLAMF8 levels were similarly elevated in collagen‐induced arthritis model mice compared with those in the healthy mice (1.13 ± 0.47 vs. 9.05 ± 2.52). Conclusions This study established the unique advantages of synovial tissue for RA research and identified metabolic and cytokine signaling pathways as important for RA development. Thus, SLAMF8 may be a potential therapeutic target for RA.

Introduction: This study aimed to investigate the differences between pregnant women with chronic hepatitis B virus (HBV) infection and intrafamilial infection and those without intrafamilial infection. Methods: HBV-DNA was extracted from the sera of 16 pregnant women with chronic hepatitis B (CHB) and their family members for gene sequencing and phylogenetic analyses. A total of 74 pregnant women with CHB were followed up from the second trimester to 3 months postpartum. Viral markers and other laboratory indicators were compared between pregnant women with CHB with and without intrafamilial infection. Results: The phylogenetic tree showed that HBV lines in the mother-spread pedigree shared a node, whereas there was an unrelated genetic background for HBV lines in individuals without intrafamilial infection. From delivery to 3 months postpartum, compared with those without intrafamilial infection, pregnant women with intrafamilial infection were related negatively to HBV-DNA (β = −0.43, 95% confidence interval [CI]: −0.76 to −0.12, p = 0.009), HBeAg (β = −195.15, 95% CI: −366.35 to −23.96, p = 0.027), and hemoglobin changes (β = −8.09, 95% CI: −15.54 to −0.64, p = 0.035) and positively to changes in the levels of alanine aminotransferase (β = 73.9, 95% CI: 38.92–108.95, p < 0.001) and albumin (β = 2.73, 95% CI: 0.23–5.23, p = 0.033). Conclusion: The mother-spread pedigree spread model differs from that of non-intrafamilial infections. Pregnant women with intrafamilial HBV infection have less hepatitis flares and liver damage, but their HBV-DNA and HBeAg levels rebound faster after delivery, than those without intrafamilial infection by the virus.

Schools are important places to carry out earthquake disaster education. Earthquake prevention and disaster reduction publicity and education in colleges and universities can help improve the results of earthquake safety education in primary and secondary schools. It is important to strengthen the awareness and skills of college students in earthquake prevention and disaster reduction, so that they can change their role to provide services to the society, and take the initiative to undertake the publicity and popularization of earthquake disasters, which is conducive to improving the ability of earthquake prevention and disaster preparedness of the whole people. In view of the problems found in the practice of popular science popularization, this paper compares the differences between universities and other academic sections of earthquake popular science popularization through questionnaire survey, analyzes the reasons and summarizes the experience, and puts forward the ways to strengthen the publicity and education of earthquake prevention and disaster reduction in universities. The analysis points out that the publicity and education of earthquake prevention and disaster reduction for college students is a continuous and dynamic project, and colleges and universities need to vigorously carry out earthquake safety education in many aspects such as concept, knowledge, skills and responsibilities, and at the same time need to rely on the strength and resources of relevant departments to improve the publicity and education effect.

AIM: To compare high or low concentration of hyaluronic acid eye drops (HY) for dry eye syndromes (DES). METHODS: Randomized controlled trials (RCTs) comparing various concentrations of HY were searched in PubMed, Embase, Web of Science, Cochrane, SinoMed, CNKI, Wanfang Database, CQVIP, and Chinese journals databases between inception and July 2023. Pooled standardized mean differences (SMD) or weighted mean difference (WMD) with 95% confidence intervals (CI) from RCTs evaluating Schirmer's I test (SIT), corneal fluorescein staining score (CFS), tear breakup time (TBUT), DES score (DESS), and Ocular Surface Disease Index (OSDI) were calculated. Sensitivity analysis, Egger's test and Meta-regression analysis were performed for all indicators. RESULTS: We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria, involving 1796 cases. High-concentrations group significantly improved the outcome of CFS according to random effects modelling (SMD, -3.37; 95%CI, -5.25 to -1.48; P=0.0005). The rest of the results were not statistically significant, including indicators such as SIT, TBUT, DESS and OSDI. CONCLUSION: For dry eyes with positive corneal staining, a high concentration of HY is recommended, whereas in other cases, a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.

Abstract Background Although physician-pharmacist collaborative clinics for diabetes management have been shown to be effective and cost-effective worldwide, there is limited understanding of the factors that influence their sustainable implementation. This study aims to identify the associated factors and provide sustainability strategy to better implement physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers in China. Methods A sample of 43 participants were participated in face-to-face, in-depth, semi-structured interviews. Consolidated Framework for Implementation Research was used to identify facilitators and barriers to implementing physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers, and to explore discriminating factors between low and high implementation units. A sustainable strategy repository based on dynamic sustainability framework was established to inform further implementation. Results This study demonstrated that clear recognition of intervention benefits, urgent needs of patients, adaptive and tailored plan, highly collaborative teamwork and leadership support were the major facilitators, while the major barriers included process complexity, large number and poor health literacy of patients in primary areas, inappropriate staffing arrangements, weak financial incentives and inadequate staff competencies. Six constructs were identified to distinguish between high and low implementation units. Sixteen strategies were developed to foster the implementation of physician-pharmacist collaborative clinics, targeting Intervention, Practice setting, and Ecological system. Conclusion This qualitative study demonstrated facilitators and barriers to implementing physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers and developed theory-based strategies for further promotion, which has the potential to improve the management of diabetes and other chronic diseases in under-resourced areas.

Abstract Background To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV, wIPV). Methods A cross-sectional investigation was conducted at four sites in Chongqing, China, healthy infants aged 60–89 days were conveniently recruited and divided into four groups according to their received primary polio vaccination schedules (2sIPV + bOPV, 2wIPV + bOPV, 3sIPV, and 3wIPV). The sero-protection and neutralizing antibody titers against poliovirus serotypes (type 1, 2, and 3) were compared after the last dose. Results There were 408 infants completed the protocol. The observed seropositivity was more than 96% against poliovirus types 1, 2, and 3 in all groups. IPV-only groups induced higher antibody titers(GMT) against poliovirus type 2 (Median:192, QR: 96–384, P

Abstract Background As is known, CD4 cell count is a significant parameter predicting HIV progression, opportunistic infections and death in HIV-infected individuals, as well was an important indicator for initiating antiretroviral therapy (ART). In China’s National Free Antiretroviral Treatment Program, people with HIV (PWH) on ART can receive a CD4 count test at least once every six months. Importantly, the baseline CD4 count (before ART initiation) is significantly correlated with ART and even prognosis, but the influence of the peak CD4 cell count on ART and/or clinical outcomes is still unknown. Methods A retrospective study was conducted among 7965 PWH who received ART from October 2003 to September 2022 at Yunnan Infectious Disease Hospital. Clinical features and laboratory data were collected and analyzed by Chi-square test, univariate and multivariate Cox regression analysis. After elimination of confounding variables, multivariate Cox regression analysis was performed to identify survival-related factors. Results Of a total of 7965 PWH in the ART treatment cohort who met the inclusion and exclusion criteria, 7939 were finally included in the subsequent analyses. First, it was found that the proportion of clinical variables, including sex, age distribution, interval from diagnosis to ART initiation, marital status, and others, was significantly different between the living and dead groups (P

Abstract Whether and how the reactive oxygen species generated by hepatic stellate cells (HSCs) promote immune evasion of hepatocellular carcinoma (HCC) remains mysterious. Therefore, investigating the function of superoxide anion (O2 •−), the firstly generated reactive oxygen species, during the immune evasion become necessary. In this work, we establish a novel in situ imaging method for visualization of O2 •− changes in HSCs based on a new two-photon fluorescence probe TPH. TPH comprises recognition group for O2 •− and HSCs targeting peptides. We observe that O2 •− in HSCs gradually rose, impairing the infiltration of CD8+ T cells in HCC mice. Further studies reveal that the cyclin-dependent kinase 4 is deactivated by O2 •−, and then cause the up-regulation of PD-L1. Our work provides molecular insights into HSC-mediated immune evasion of HCC, which may represent potential targets for HCC immunotherapy.