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Abstract Homozygous familial hypercholesterolemia (HoFH), is a rare genetic disorder characterized by dual mutations in the low-density lipoprotein receptor (LDLR) gene, leading to dysfunctional or absent LDLRs, often accompanied by severe premature Atherosclerotic Cardiovascular Disease (ASCVD) and exhibiting refractoriness to aggressive pharmacological interventions. Double filtration plasmapheresis (DFPP), a form of lipoprotein apheresis (LA), has been effectively utilized as an adjunctive treatment modality to reduce serum LDL-C levels in refractory cases of HoFH. Here, we report a case of a 36-year-old female with HoFH who developed xanthomas on her limbs and waist at age 7. Despite maximum-tolerated doses of statins from age 32, combined with ezetimibe and evolocumab, her LDL-C levels remained critically elevated at 12–14 mmol/L. Her genetic testing confirmed a homozygous LDLR mutation. At 35 years old, she experienced exertional chest pain, and percutaneous coronary intervention revealed severe calcific left main stenosis, necessitating stent implantation. Subsequently, she initiated once every 1–2 months DFPP. Pre-DFPP, her LDL-C and total cholesterol (TC) levels were 13.82 ± 3.28 and 15.45 ± 0.78 mmol/L, respectively. Post-DFPP, her LDL-C and TC levels significantly decreased to 2.43 ± 0.33 mmol/L (81.76 ± 4.11% reduction) and 3.59 ± 0.41 mmol/L (76.76 ± 2.75% reduction), respectively. Lipoprotein (a) and triglycerides also decreased by 89.10 ± 1.39% and 42.29 ± 15.68%,respectively. Two years later, there was no progression of coronary artery disease, and her symptoms and xanthomas regressed significantly. Collectively, DFPP effectively reduces LDL-C levels in refractory cases of HoFH and contributes to delaying ASCVD progression, representing an efficacious adjunctive therapeutic modality.

Abstract Mesenchymal stem cells (MSCs) in tumor microenvironment (TME) are crucial for the initiation, development, and metastasis of cancer. The impact and mechanism of MSCs on bladder cancer are uncertain. Here we analyzed 205 patient samples to explore the relationships between tumor-stroma ratio and clinicopathological features. A co-culture model and nude mouse transplantation were used to explore the biological roles and molecular mechanisms of MSCs on bladder cancer cells. We found that a high tumor-stroma ratio was significantly associated with a larger tumor size and higher T stage, pathological grade, number of vascular invasions, and poor overall survival. MSCs in TME promoted the ability of bladder cancer cells to proliferate, migrate, and invade in vitro and in vivo. Next, we demonstrated that MSCs enhance mitochondrial autophagy and mitochondrial biogenesis of bladder cancer cells, and increase energy production, thereby promoting bladder cancer cell progression. Kynurenine (Kyn) produced by MSCs could enhance mitochondrial function by activating the AMPK pathway. IDO1 inhibitor could reverse the tumor‑promoting effects of MSCs in vitro and in vivo. Our results demonstrated that tryptophan metabolites Kyn of MSCs in TME could enhance mitochondrial function by activating the AMPK pathway, thereby promoting bladder cancer cell progression.

Abstract The prognosis of extensive-stage small cell lung cancer is usually poor. In this study, a combined model based on pre-treatment CT radiomics and clinical features was constructed to predict the OS of extensive-stage small cell lung cancer after chemotherapy with immunotherapy.Clinical data of 111 patients with extensive stage small-cell lung cancer who received first-line immunotherapy combined with chemotherapy in our hospital from December 2019 to December 2021 were retrospectively collected. Finally, 93 patients were selected for inclusion in the study, and CT images were obtained through PACS system before treatment. All patients were randomly divided into a training set (n = 66) and a validation set (n = 27). Images were imported into ITK-SNAP to outline areas of interest, and Python software was used to extract radiomics features. A total of 1781 radiomics features were extracted from each patient’s images. The feature dimensions were reduced by MRMR and LASSO methods, and the radiomics features with the greatest predictive value were screened. The weight coefficient of radiomics features was calculated, and the linear combination of the feature parameters and the weight coefficient was used to calculate Radscore. Univariate cox regression analysis was used to screen out the factors significantly associated with prognosis from the radiomics and clinical features, and multivariate cox regression analysis was performed to establish the prognosis prediction model of extensive stage small cell lung cancer. The degree of metastases was selected as a significant clinical prognostic factor by univariate cox regression analysis. Seven radiomics features with significance were selected by LASSO-COX regression analysis, and the Radscore was calculated according to the coefficient of the radiomics features. An alignment diagram survival prediction model was constructed by combining Radscore with the number of metastatic lesions. The study population was stratified into those who survived less than 11 months, and those with a greater than 11 month survival. The C-index was 0.722 (se = 0.044) and 0.68(se = 0.074) in the training and the validation sets, respectively. The Log_rank test results of the combination model were as follows: training set: p

Abstract Background BCR-ABL is a constitutively active tyrosine kinase that stimulates multiple downstream signaling pathways to promote the survival and proliferation of chronic myeloid leukemia (CML) cells. The clinical application of specific BCR-ABL tyrosine kinase inhibitors (TKIs) has led to significantly improved prognosis and overall survival in CML patients compared to previous treatment regimens. However, direct targeting of BCR-ABL does not eradicate CML cells expressing T315I-mutated BCR-ABL. Our previous study revealed that inhibiting CREB binding protein (CBP) is efficacious in activating β-catenin/p300 signaling, promoting cell differentiation and inducing p53/p21-dependent senescence regardless of BCR-ABL mutation status. We hypothesize that the specific inhibition of CBP may represent a novel strategy to promote β-catenin/p300-mediated differentiation and suppress cancer cell proliferation for treating CML patients. Methods The anticancer efficacy of PBA2, a novel CBP inhibitor, in CML cells expressing wild-type or T315I-mutated BCR-ABL was investigated in vitro and in vivo. Cell differentiation was determined by the nitroblue tetrazolium (NBT) reduction assay. The extent of cellular senescence was assessed by senescence-associated β-galactosidase (SA-β-Gal) activity. Cytotoxicity was measured by MTS assay. RNA interference was performed to evaluate the cell proliferation effects of CBP knockdown. The interaction of β-catenin and CBP/p300 was examined by co-immunoprecipitation assay. Results PBA2 exhibited significantly higher anticancer effects than imatinib in CML cells harboring either wild-type or T315I-mutated BCR-ABL both in vitro and in vivo. Mechanistically, PBA2 reduced CBP expression and promoted β-catenin-p300 interaction to induce cell differentiation and senescence. Conclusion Our data supported the rational treatment of CML by inhibiting the β-catenin/CBP pathway regardless of BCR-ABL mutation status.

Abstract Given the surpassing of the Shockley-Quiesser efficiency limit in conventional p-n junction photovoltaic effect, bulk photovoltaic effect (BPVE) has garnered significant research interest. However, the BPVE primarily focuses on a narrow wavelength range, limiting its potential applications. Here we report a giant infrared bulk photovoltaic effect in tellurene (Te) for broad-spectrum neuromodulation. The generated photocurrent in uniformly illuminated Te excludes other photoelectric effects and is attributed to the BPVE. The bulk photovoltaic wavelength in Te spans a wide range from the ultraviolet (390 nm) to the mid-infrared (3.8 µm). Moreover, the photocurrent density of 70.4 A cm−2 under infrared light simulation outperforms that in previous ultraviolet and visible semiconductors as well as infrared semimetals. Te attached to the dendrites or somata of the cortical neurons successfully elicit action potentials under broad-spectrum light irradiation. This work lays the foundation for the further development of infrared BPVE in narrow bandgap materials.

Abstract Background X-linked agammaglobulinemia (XLA), also referred to as Bruton’s tyrosine kinase deficiency, is a rare genetic disorder that affects the immune system. We conducted genetic analysis on patients suffering from immunodeficiency by utilizing Next-Generation Sequencing techniques, as well as their closest relatives, to facilitate accurate diagnosis, offer genetic counseling services, and enhance our comprehension of XLA.

Objective: To establish a method for simultaneous determination of nine active components in the fermented tea of Trametes versicolor, and analyze the changes of nine active components and antioxidant activities fermentation before and after. Methods: Using gradient elution at a flow rate of 1.0 mL/min, an Agilent C18 column (4.6 mm×250 mm, 5 μm) was used with a mobile of 0.05% phosphoric acid solution (A) and acetonitrile (B) as the mobile phase. The detection wavelength was 280 nm and the column temperature was 30 ℃. Results: Compared with the control group unfermented green tea, there was no significant change in the caffeine content of fermented tea. The increasing rates of gallic acid, theobromine and gallatechin gallate content in fermented tea were 0.4613%, 0.3118% and 0.5770%, respectively. The decreasing rates of egallatechin, theophylline, epigallocatechin, epicatechin and epigallocatechin gallate content in fermented tea were 0.0156%, 0.0178%, 1.2938%, 1.1062% and 4.0241%, respectively. In vitro antioxidant activity studies revealed that DPPH· scavenging capacity and ·OH scavenging capacity were significantly (P

Abstract Background Follicular cysts contribute significantly to reproductive loss in high-yield dairy cows. This results from the death of follicular granulosa cells (GCs) caused by oxidative stress. Quercetin is known to have significant antioxidant and anti-apoptotic effects. However, the effect of quercetin on follicular cysts has yet been elucidated. Therefore, this study aimed to explore the anti-oxidant and anti-apoptosis effects and potential molecular mechanisms of quercetin in H2O2-induced primary cow GCs and 3-nitropropionic acid (3-NPA)-induced mouse model of oxidative stress and thus treat ovarian cysts in dairy cows. Results In this study, compared with estrus cows, cows with follicular cysts showed heightened levels of oxidative stress and increased follicular cell apoptosis, while autophagy levels were reduced. A model of oxidative stress was induced in vitro by H2O2 and showed significant increases in apoptosis together with reduced autophagy. These effects were significantly ameliorated by quercetin. Effects similar to those of quercetin were observed after treatment of cells with the reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC). Further investigations using chloroquine (autophagy inhibitor), rapamycin (autophagy activator), selisistat (SIRT1 inhibitor), and compound C (AMPK inhibitor) showed that chloroquine counteracted the effects of quercetin on oxidative stress-induced apoptosis, while rapamycin had the same effect as quercetin. In addition, the SIRT1/AMPK pathway inhibitors antagonized quercetin-mediated mitigation of the effects of oxidative stress on increased apoptosis and reduced autophagy. Consistent with the results in vitro, in mouse ovarian oxidative stress model induced by 3-NPA, quercetin activated autophagy through the SIRT1/AMPK signaling pathway, while alleviating oxidative stress damage and inhibiting apoptosis in mouse ovaries. Conclusions These findings indicate that quercetin can inhibit apoptosis in GCs and restore ovarian function by activating autophagy through the SIRT1/ROS/AMPK signaling pathway, suggesting a new direction for the treatment of ovarian follicular cysts in high-yield dairy cows.

Abstract Background Off-label intranasal administration of injectable dexmedetomidine has been widely applied in the pediatric sedation setting. However, the development of an improved drug delivery system that is easy to use is needed. We developed a novel dexmedetomidine nasal spray that can be administered directly without dilution or configuration for pediatric pre-anesthetic sedation. This nasal spray has a fixed dose and is stable during storage. To the best of our knowledge, this is the first licensed nasal spray preparation of dexmedetomidine worldwide. Objective To evaluate the pre-anesthetic sedation efficacy and safety of the novel dexmedetomidine nasal spray in children. Methods The study was conducted at 11 sites in China between 24 November 2021 and 20 May 2022 and was registered in ClinicalTrials.gov (NCT05111431, first registration date: 20/10/2021). Subjects (n = 159) between 2 and 6 years old who were to undergo elective surgery were randomized to the dexmedetomidine group (n = 107) or the placebo group (n = 52) in a 2:1 ratio. The dosage was 30 µg or 50 µg based on the stratified body weight. The primary outcome measure was the proportion of subjects who achieved the desired child-parent separation and Ramsay scale ≥ 3 within 45 min of administration. Safety was monitored via the assessments of adverse events, blood pressure, heart rate, respiratory rate and blood oxygen saturation. Results The proportion of subjects achieving desired parental separation and Ramsay scale ≥ 3 within 45 min was significantly higher in the dexmedetomidine group (94.4%) vs the placebo group (32.0%) (P

Transcutaneous implants that penetrate through skin or mucosa are susceptible to bacteria invasion and lack proper soft tissue sealing. Traditional antibacterial strategies primarily focus on bacterial eradication, but excessive exposure to bactericidal agents can induce noticeable tissue damage. Herein, a rechargeable model (HPI-Ti) was constructed using perylene polyimide, an aqueous battery material, achieving temporal-sequence regulation of bacterial killing and soft tissue sealing. Charge storage within HPI-Ti is achieved after galvanostatic charge, and chemical discharge is initiated when immersed in physiological environments. During the early discharge stage, post-charging HPI-Ti demonstrates an antibacterial rate of 99.96 ± 0.01 % for 24 h, preventing biofilm formation. Contact-dependent violent electron transfer between bacteria and the material causes bacteria death. In the later discharge stage, the attenuated discharging status creates a gentler electron-transfer micro-environment for fibroblast proliferation. After discharge, the antibacterial activity can be reinstated by recharge against potential reinfection. The antibacterial efficacy and soft tissue compatibility were verified in vivo. These results demonstrate the potential of the charge-transfer-based model in reconciling antibacterial efficacy with tissue compatibility.

Objective To conduct Rh blood group serological testing and third-generation sequencing(TGS) on 22 RhD variant voluntary blood donors in Chongqing and explore the phenotypic distribution and genotyping of RhD variants in Chongqing. Methods From January to August 2023, individuals who participated in blood donation in our blood center were selected as the study objects. RhD variant phenotype identification was performed using routine serological methods. Once the RhD variants were identified, tests on different antigenic epitopes of RhD were conducted using a D-screen assay kit. Furthermore, after the genomic DNA from 22 RhD variant blood samples was extracted, imbraided primers design and multi-segment amplification and splicing were used to sequence the full-length RHD gene for TGS. The RHD gene sequence was analyzed using SnapGene software. Results Among the 22 RhD variants, 8 were DVI type 3 (36.36%), with the main mutation of RHD-CE (3-6)-D hybrid allele. Six cases (27.27%) showed partial weak D15 type, with the main mutation of c.845G>A. There were 6 cases of Asia type Del (27.27%), with the main mutation of c.1227G>A. One case was weak D17 type with a mutation of c.340C>T and 1 case speculated to be partial D (c.491A>T, p. Asp164Val, missense mutation). Conclusion The most common RhD variant phenotype among blood donors in Chongqing is DVI type 3, and the full-length haplotype sequence of RHD variant alleles can be obtained by Pacific Bioscience single-molecule real-time sequencing(SMRT).

Objective To explore the causes and nursing strategies of red blood cell spillage in apheresis platelet donors, so as to avoid adverse reactions to blood donation and platelet discarding and improve blood donation services. Methods A nursing flowchart for red blood cell spillage was developed based on literature. One case of red blood cell spillage in a apheresis platelet donor as attached, and corresponding literature review was conducted. Results After the nursing intervention through the nursing flowchart of red cell spillage, platelet apheresis was successfully conducted. The donor felt good and did not experience any adverse reaction to blood donation, and with no more red blood cell spillage. By reviewing relevant literature, the incidence, principles, causes, treatments, prevention of adverse reactions to blood donation and psychological care methods of red blood cell spillage were systematically summarized. Conclusion Red blood cell spillage in apheresis platelet donors occurs occasionally, and a flowchart of care for red blood cell spillage can help blood station staff quickly identify the cause and handle it correctly to avoid mishandling whicn can result in adverse reactions or discarding of platelets.

Abstract Although thrombocytopenia on admission to the ICU is associated with increased in-hospital mortality in septic patients, the role of longitudinally measured platelet counts, which are dynamically changing, is unclear. We aimed to identify patterns of dynamic platelet count trajectories and evaluate their association with outcomes and thrombocytopenia in septic patients. We tested the longitudinal platelet trajectory patterns of sepsis patients within the first four days of ICU admission in the MIMIC-IV database and their association with 28-day mortality, and independently validated our findings in the eICU-CRD database. Statistical methods used included multivariate regression, propensity score analysis, doubly robust estimation, gradient boosting model, and inverse probability weighting to ensure the robustness of our findings. A total of 22,866 septic patients were included in our study. The trajectory analysis categorizes patients into ascending (AS), stable (ST), or descending (DS) patterns. The risk of 28-day mortality was increased in the DS patients (OR = 2.464, 95%CI 1.895–3.203, p

Abstract Background Hepatitis B virus (HBV) infection is a major concern regarding blood safety in countries with a high HBV prevalence, such as China. We aimed to understand the prevalence of HBV infection among blood donors in Chongqing and provide an important basis for developing appropriate blood screening strategies. Methods Dual enzyme-linked immunosorbent assays (ELISAs) for hepatitis B surface antigen (HBsAg) were conducted in parallel with nucleic acid testing (NAT) of donors. All HBsAg-reactive and/or HBV DNA-positive blood samples were tested for HBsAg and hepatitis B DNA levels. Results A total of 117,927 blood donor samples were collected from the Chongqing Blood Center between April 2020 and November 2020. In total, 473 HBV-ineligible samples were retained for HBsAg and DNA confirmation. A total of 272 samples were confirmed to be HBsAg+, including 2 HBV DNA − and 270 HBV DNA + samples. A total of 201 donations were HBsAg−, including 72 HBV DNA − samples. The rate of HBV infection was 65.33% (309/473) in men, which was significantly higher than that in women (p

Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is a severe disease with substantial economic consequences for the swine industry. The DEAD-box helicase 3 (DDX3X) is an RNA helicase that plays a crucial role in regulating RNA metabolism, immunological response, and even RNA virus infection. However, it is unclear whether it contributes to PRRSV infection. Recent studies have found that the expression of DDX3X considerably increases in Marc-145 cells when infected with live PRRSV strains Ch-1R and SD16; however, it was observed that inactivated viruses did not lead to any changes. By using the RK-33 inhibitor or DDX3X-specific siRNAs to reduce DDX3X expression, there was a significant decrease in the production of PRRSV progenies. In contrast, the overexpression of DDX3X in host cells substantially increased the proliferation of PRRSV. A combination of transcriptomics and metabolomics investigations revealed that in PRRSV-infected cells, DDX3X gene silencing severely affected biological processes such as ferroptosis, the FoxO signalling pathway, and glutathione metabolism. The subsequent transmission electron microscopy (TEM) imaging displayed the typical ferroptosis features in PRRSV-infected cells, such as mitochondrial shrinkage, reduction or disappearance of mitochondrial cristae, and cytoplasmic membrane rupture. Conversely, the mitochondrial morphology was unchanged in DDX3X-inhibited cells. Furthermore, silencing of the DDX3X gene changed the expression of ferroptosis-related genes and inhibited the virus proliferation, while the drug-induced ferroptosis inversely promoted PRRSV replication. In summary, these results present an updated perspective of how PRRSV infection uses DDX3X for self-replication, potentially leading to ferroptosis via various mechanisms that promote PRRSV replication.

Abstract Background Accumulating studies have highlighted the significant role of circulating metabolomics in the etiology of reproductive system disorders. However, the causal effects between genetically determined metabolites (GDMs) and reproductive diseases, including primary ovarian insufficiency (POI), polycystic ovary syndrome (PCOS), and abnormal spermatozoa (AS), still await thorough clarification. Methods With the currently most comprehensive genome-wide association studies (GWAS) data of metabolomics, systematic two-sample Mendelian randomization (MR) analyses were conducted to disclose causal associations between 1,091 blood metabolites and 309 metabolite ratios with reproductive disorders. The inverse-variance weighted (IVW) method served as the primary analysis approach, and multiple effective MR methods were employed as complementary analyses including MR-Egger, weighted median, constrained maximum likelihood (cML-MA), contamination mixture method, robust adjusted profile score (MR-RAPS), and debiased inverse-variance weighted method. Heterogeneity and pleiotropy were assessed via MR-Egger intercept and Cochran’s Q statistical analysis. Outliers were detected by Radial MR and MR-PRESSO methods. External replication and metabolic pathway analysis were also conducted. Results Potential causal associations of 63 GDMs with POI were unearthed, and five metabolites with strong causal links to POI were emphasized. Two metabolic pathways related to the pathogenesis of POI were pinpointed. Suggestive causal effects of 70 GDMs on PCOS were detected, among which 7 metabolites stood out for strong causality with elevated PCOS risk. Four metabolic pathways associated with PCOS mechanisms were recognized. For AS, 64 GDMs as potential predictive biomarkers were identified, particularly highlighting two metabolites for their strong causal connections with AS. Three pathways underneath the AS mechanism were identified. Multiple assessments were conducted to further confirm the reliability and robustness of our causal inferences. Conclusion By extensively assessing the causal implications of circulating GDMs on reproductive system disorders, our study underscores the intricate and pivotal role of metabolomics in reproductive ill-health, laying a theoretical foundation for clinical strategies from metabolic insights.

Abstract Circular RNA (circRNA) is thought to mediate the occurrence and development of human cancer and usually acts as a tiny RNA (miRNA) sponge to regulate downstream gene expression. However, it is not clear whether and how circACVR2A (hsa_circ_0001073) is involved in the progression of HCC. The purpose of this study is to clarify the potential role and molecular mechanism of circACVR2A in regulating the progression of hepatocellular carcinoma cells (HCC). The abundance of related proteins in circACVR2A, microRNA (miR511-5p) and PI3K-Akt signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) or Western blotting. Cell viability, invasion and apoptosis were analyzed by CCK-8, Transwell analysis and Tunel staining, respectively. The interaction between circACVR2A and microRNA was evaluated by double luciferase reporter gene assay. The results showed that circACVR2A was highly expressed in hepatocellular carcinoma cell lines. Our in vivo and in vitro data showed that circACVR2A promoted the proliferation, migration and invasion of HCC. In terms of mechanism, we found that circACVR2A can directly interact with miR511-5p and act as a miRNA sponge to regulate the expression of related proteins in PI3K-Akt signaling pathway. In HCC, circACVR2A can mediate miR-511-5p/mRNA network to activate PI3K signal pathway. This shows that the molecular regulatory network with circACVR2A as the core is a new potential target for diagnosis and treatment of hepatocellular carcinoma.

Abstract The separation and purification of chemical raw materials, particularly neutral compounds with similar physical and chemical properties, represents an ongoing challenge. In this study, we introduce a class of water-soluble macrocycle compound, calix[2]azolium[2]benzimidazolone (H), comprising two azolium and two benzimidazolone subunits. The heterocycle subunits form a hydrophobic binding pocket that enables H1 to encapsulate a series of neutral guests in water with 1:1 or 2:1 stoichiometry, including aldehydes, ketones, and nitrile compounds. The host-guest complexation in the solid state was further confirmed through X-ray crystallography. Remarkably, H1 was shown to be a nonporous adaptive crystal material to separate valeraldehyde from the mixture of valeraldehyde/2-methylbutanal/pentanol with high selectivity and recyclability in the solid states. This work not only demonstrates that azolium-based macrocycles are promising candidates for the encapsulation of organic molecules but also shows the potential application in separation science.

Abstract The deep ultraviolet (DUV) micro-light emitting diode (μLED) has serious electron leakage and low hole injection efficiency. Meanwhile, with the decrease in the size of the LED chip, the plasma-assisted dry etching process will cause damage to the side wall of the mesa, which will form a carrier leakage channel and produce non-radiative recombination. All of these will reduce the photoelectric performance of μLED. To this end, this study introduces polarized bulk charges into the hole supply layer (p-HSL) and the electron supply layer (n-ESL) respectively (dual-polarized structure) of the DUV μLED at an emission wavelength of 279 nm to enhance the binding of carriers and increase the injection efficiency of carriers. This is because the polarization-induced bulk charge can shield the polarized sheet charge on the interface and reduce the polarization electric field. The reduced polarization electric field in p-HSL can increase the effective barrier height of the conduction band in the p-type region and reduce the effective barrier height of the valence band. The decrease in the polarized electric field of n-HSL can reduce the thermal velocity of electrons, thereby enhancing the electron injection efficiency, reducing the Shockley–Read–Hall (SRH) recombination, and increasing the effective barrier height of the valence band. The study results indicate that the electron concentration and hole concentration of a μLED with dual polarization were increased by 77.93% and 93.6%, respectively. The optical power and maximum external quantum efficiency of μLED reached 31.04 W/cm2 and 2.91% respectively, and the efficiency droop is only 2.06% at 120 A/cm2. These results provide a new approach to solving the problem of insufficient carrier injection and SRH recombination in high-performance DUV μLEDs.

Abstract Background There is evidence suggesting that Notch1 signaling pathway contributes to the development of hand, foot, and mouth disease (HFMD); however, the role of Notch1 gene polymorphisms in the severity of coxsackievirus A6 (CVA6)-related HFMD remains unclear. This study aimed to investigate the correlation between Notch1 gene polymorphisms and the severity of CVA6-related HFMD. Methods A total of 196 patients (Chinese Han population) diagnosed with CVA6-related HFMD through nucleic acid testing were included in this study. Among them, 97 patients were classified as severe cases, while 99 cases were categorized as mild. The mRNA levels of Notch1 in the peripheral blood leukocytes of HFMD patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was utilized for genotyping of rs3124599, rs3124603, and rs3124591. Results The frequencies of rs3124599 alleles were G (39.0%) and A (61.0%), while the frequencies of rs3124599 genotypes were GG (12.2%), GA (53.6%), and AA (34.2%), respectively. In the recessive model, the frequency of rs3124599 AA genotypes significantly increased in severe patients, compared to mild patients (P 0.05), no additional statistical analysis was performed. After adjusting for age and sex, patients with rs3124599 AA genotype had a significantly higher risk of severe HFMD in comparison to G allele carriers (GA/GG), with an odds ratio (95% confidence interval) of 2.010 (1.094, 3.691). Meanwhile, the mRNA levels of Notch1 were found to be significantly higher in severe patients compared to mild patients (P

Abstract Background Ferroptosis is associated with the pathological progression of hemorrhagic injury and ischemia–reperfusion injury. According to our previous study, exosomes formed through bone marrow mesenchymal stem cells modified with miR-340-3p (MB-exos) can restore damaged endometrium. However, the involvement of ferroptosis in endometrial injury and the effect of MB-exos on ferroptosis remain elusive. Methods The endometrial injury rat model was developed. Exosomes were obtained from the supernatants of bone marrow mesenchymal stromal cells (BMSCs) and miR-340/BMSCs through differential centrifugation. We conducted RNA-seq analysis on endometrial tissues obtained from the PBS and MB-exos groups. Ferroptosis was induced in endometrial stromal cells (ESCs) by treating them with erastin or RSL3, followed by treatment with B-exos or MB-exos. We assessed the endometrial total m6A modification level after injury and subsequent treatment with B-exos or MB-exos by methylation quantification assay. We performed meRIP-qPCR to analyze m6A modification-regulated endogenous mRNAs. Results We reveal that MB-exos facilitate the injured endometrium to recover by suppressing ferroptosis in endometrial stromal cells. The injured endometrium showed significantly upregulated N 6-methyladenosine (m6A) modification levels; these levels were attenuated by MB-exos through downregulation of the methylase METTL3. Intriguingly, METTL3 downregulation appears to repress ferroptosis by stabilizing HMOX1 mRNA, thereby potentially elucidating the mechanism through which MB-exos inhibit ferroptosis in ESCs. We identified YTHDF2 as a critical m6A reader protein that contributes to HMOX1 mRNA degradation. YTHDF2 facilitates HMOX1 mRNA degradation by identifying the m6A binding site in the 3′-untranslated regions of HMOX1. In a rat model, treatment with MB-exos ameliorated endometrial injury-induced fibrosis by inhibiting ferroptosis in ESCs. Moreover, METTL3 short hairpin RNA-mediated inhibition of m6A modification enhanced the inhibitory effect of MB-exos on ferroptosis in endometrial injury. Conclusions Thus, these observations provide new insights regarding the molecular mechanisms responsible for endometrial recovery promotion by MB-exos and highlight m6A modification-dependent ferroptosis inhibition as a prospective therapeutic target to attenuate endometrial injury.

Abstract Background This study aims to analyze the efficacy of metformin on carotid intima media thickness (CIMT) and flow-mediated dilation (FMD) for patients with polycystic ovary syndrome (PCOS). Methods A literature search of PubMed, Embase, and the Cochrane Library from inception to December 2023 was conducted. Then, after studies selection and data extraction, the mean difference (MD) with a 95% confidence interval (CI) was used to evaluate metformin efficacy in CIMT and FMD for PCOS patients. Heterogeneity was investigated through subgroup and sensitivity analysis. The protocol of our study has been registered in PROSPERO (CRD42024497239). Results A total of 12 studies with 248 patients were included. CIMT was lower in the endpoint group (after metformin) compared with the baseline group (before metformin) (MD = -0.11, 95% CI = -0.21 to -0.01, p = 0.04). FMD was higher in the endpoint group compared with the baseline group (MD = 3.25, 95% CI = 1.85 to 4.66, p

Abstract Background kangaroo care (KC), endorsed by the World Health Organization, is an evidence-based intervention that plays a pivotal role in mitigating preterm infant mortality and morbidity. However, this intervention has not been fully integrated into healthcare systems in China. This study aimed to gain insight into parents’ perceptions and experiences of KC for preterm infants to contribute to the KC implementation on a larger scale. Methods This study employed a descriptive qualitative design, using face-to-face, semi-structured, in-depth interviews. Fifteen parents participating in KC for preterm infants in the neonatal intensive care units (NICUs) were purposively sampled from four hospitals across four cities in Zhejiang Province, China. Thematic analysis was employed to analyze the data. Results Four themes and twelve subthemes regarding the parents’ perceptions and experiences about KC were identified. The four themes included: (1) Low motivation upon initial engagement with KC, (2) Dynamic fluctuations of emotional states during KC, (3) Unexpected gains, and (4) Barriers to participation. Conclusions Parents’ perceptions and experiences of KC was a staged process, with parents exhibiting distinct cognitive patterns and unique experiences at each stage. Overall, as KC progresses, parents’ experiences tended to become increasingly positive, despite potential obstacles encountered along the way. To enhance the implementation of KC, healthcare providers could utilize prenatal and postnatal education programs. These programs aim to enhance the understanding of KC among parents of preterm infants, fostering sustained engagement in KC practices.

Abstract Establishing prediction models of pregnancy outcomes for recurrent pregnancy loss women at specific gestational weeks will provide patients and physicians with more precise information, ultimately leading to time and cost savings associated with unnecessary revisits. Therefore, our aim was to develop a prediction model for first trimester pregnancy loss in RPL patients. We used ultrasound indices during the first trimester of pregnancy in combination with demographic characteristics and commonly used serum markers. The independent risk factors for each week were as follows: age and P in the fifth week; age, mGSD and CRL in the sixth week; age, hCG and CRL in the seventh week; CRL in the eighth week; mGSD and CRL in ninth week. The corresponding AUC was 0.671, 0.796, 0.872, 0.871, 0.813, respectively. There is a linear relationship between age and first trimester pregnancy loss. hCG 48.3 mm in ninth gestational week was associated with a higher risk of pregnancy loss. These models and thresholds may help physicians and patients make more informed decisions together. Further studies are needed to confirm the results.

Abstract Background Many long noncoding RNAs (lncRNAs) with altered expression significantly influence colorectal cancer (CRC) progression and behavior. The functions of many lncRNAs in CRC are not clear yet. This study aimed to discover novel lncRNA entities and comprehensively examine and validate their roles and underlying molecular mechanisms in CRC. Methods Tissue samples, both tumourous and non-tumourous, from three CRC patients were submitted for sequencing. Following expression validation in samples from ten patients and four CRC cell lines. The lncRNA KCNMA1-AS2 was synthesized by In-vitro transcription RNA synthesis and the lncRNA was directly transfected into CRC cell lines to overexpress. Functional assays including MTT proliferation assay, Annexin-V/propidium iodide apoptosis assay, wound healing migration assay and cell cycle assays were performed to evaluate the effect of overexpression of KCNMA1-AS2. Furthermore, the binding of KCNMA1-AS2 to miR-1227-5p was confirmed using dual luciferase reporter assays and qPCR analyses. Subsequent bioinformatics analyses identified 58 potential downstream targets of miR-1227-5p across three databases. Results In this study, we identified the lncRNA KCNMA1-AS2, the expression of which was down-regulated consistently in cancer tissues and CRC cell lines compared to non-cancerous tissues. The overexpression of lncRNA KCNMA1-AS2 led to significant reduction in CRC cell proliferation and migration, increase in cell apoptosis, and more cells arrested in S phase. Additionally, the interaction between KCNMA1-AS2 and miR-1227-5p was confirmed through dual luciferase reporter assay and qPCR analysis. It is also putatively predicted that MTHFR and ST8SIA2 may be linked to CRC based on bioinformatics analyses. Conclusions LncRNA KCNMA1-AS2 exhibited distinct gene expression patterns in both CRC tissue and cell lines, impacting various cellular functions while also acting as a sponge for miR-1227-5p.The findings spotlight lncRNA KCNMA1-AS2 as a potential marker for diagnosis and treatment of CRC.

Abstract This study aimed to investigate the effects of tea green leafhopper damage on the sensory quality and metabolite composition of Oriental Beauty by using tea leaves from different varieties of tea plants and processing factories. The results indicated that tea green leafhopper damage could reduce bitterness and increase the level of fruity aroma, which was related to the content changes of catechin components and alcohol substances. Furthermore, the tea green leafhopper salivary treatment experiment revealed that the decrease of catechin content and increase of theaflavin content were mainly influenced by the action of saliva and mechanical injury, and changes in volatile components such as linalool oxidation were responsible for the alteration in aroma. These findings provide a theoretical reference for the aroma formation and quality improvement of Oriental Beauty.

Abstract Background Nursing work in the Eye, Ear, Nose, and Throat (EENT) emergency department is highly specialised and faces significant challenges. Therefore, a high level of nursing competence is necessary for nurses. To develop core competencies, a systematic and standardised training program is required. This study aims to construct a standardised, systematic, and professional training program for nurses working in the EENT emergency department in China. Methods Based on a literature review and semi-structured interviews, the training scheme draft was developed according to the theoretical framework of core competency for emergency nurses. From July 2023 to October 2023, a total of 21 experts including clinical experts, and nursing experts were selected to conduct 2 rounds of Delphi consultation to construct the training program for EENT emergency nurses. Results The effective response rate for 2 rounds of expert consultation was 100%. The expert authority coefficient was 0.905, and Kendall’s W coefficients were found to be 0.359 and 0.340, respectively. The coefficients of variation for each item of the second round of expert consultation ranged from 0 to 0.19. The finalised training program for EENT emergency nurses consisted of 4 first-level indexes (training objectives, training management, training contents, and training assessment). The training objectives included 3 secondary indicators and 16 tertiary indicators. Training management included 5 secondary indicators and 8 tertiary indicators. Training contents included 4 secondary indicators and 16 tertiary indicators. Training assessment included 3 secondary indicators and 6 tertiary indicators. Conclusion This study systematically and comprehensively explores the cultivation of nurses working in the EENT emergency department from the aspects of training objectives, training management, training contents, and training assessment. This training program is based on the theoretical framework of core competency standards for emergency nurses. It is in line with the actual needs of the clinic, and the training program is scientific and reliable, which can be promoted nationwide to provide a reference basis for the improvement of the training of emergency specialist nurses. Trial registration Not applicable.

Abstract Background Obesity has become a major global public health challenge. Studies examining the associations between different obesity patterns and the risk of nonalcoholic fatty liver disease (NAFLD) are limited. This study aimed to investigate the relationships between different obesity patterns and the risk of NAFLD in a large male population in the US. Methods Data from the 2017 to March 2020 National Health and Nutrition Examination Survey (NHANES) were utilized. Liver steatosis and fibrosis were assessed with FibroScan using the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM). Steatosis was identified with a CAP value of 248 dB/m or higher. Abdominal obesity was defined by a waist circumference (WC) of 102 cm or more for males and 88 cm or more for females. Overweight was defined as a body mass index (BMI) of 24.0 kg/m2 and above. General obesity was identified with a BMI of 28.0 kg/m2 or higher. Obesity status was categorized into four types: overweight, general obesity, abdominal obesity, and combined obesity. Multivariate logistic regression, adjusting for potential confounders, was used to examine the link between obesity patterns and NAFLD risk. Subgroup analysis further explored these associations. Results A total of 5,858 adults were included. After multivariable adjustment, compared to the normal weight group, the odds ratios (ORs) [95% confidence interval (CI)] for NAFLD in individuals with overweight, general obesity, abdominal obesity, and combined obesity were 6.90 [3.74–12.70], 2.84 [2.38–3.39], 3.02 [2.02–4.51], and 9.53 [7.79–11.64], respectively. Subgroup analysis showed the effect of different obesity patterns on NAFLD risk was stable among individuals with different clinical conditions. In the fully adjusted multivariate logistic regression model, WC was positively associated with NAFLD risk (OR: 1.48; 95% CI: 1.42–1.53; P

Abstract Objectives To establish an MRI-based radiomics model for predicting the microvascular invasion (MVI) status of cHCC-CCA and to investigate biological processes underlying the radiomics model. Methods The study consisted of a retrospective dataset (82 in the training set, 36 in the validation set) and a prospective dataset (25 patients in the test set) from two hospitals. Based on the training set, logistic regression analyses were employed to develop the clinical-imaging model, while radiomic features were extracted to construct a radiomics model. The diagnosis performance was further validated in the validation and test sets. Prognostic aspects of the radiomics model were investigated using the Kaplan–Meier method and log-rank test. Differential gene expression analysis and gene ontology (GO) analysis were conducted to explore biological processes underlying the radiomics model based on RNA sequencing data. Results One hundred forty-three patients (mean age, 56.4 ± 10.5; 114 men) were enrolled, in which 73 (51.0%) were confirmed as MVI-positive. The radiomics model exhibited good performance in predicting MVI status, with the area under the curve of 0.935, 0.873, and 0.779 in training, validation, and test sets, respectively. Overall survival (OS) was significantly different between the predicted MVI-negative and MVI-positive groups (median OS: 25 vs 18 months, p = 0.008). Radiogenomic analysis revealed associations between the radiomics model and biological processes involved in regulating the immune response. Conclusion A robust MRI-based radiomics model was established for predicting MVI status in cHCC-CCA, in which potential prognostic value and underlying biological processes that regulate immune response were demonstrated. Critical relevance statement MVI is a significant manifestation of tumor invasiveness, and the MR-based radiomics model established in our study will facilitate risk stratification. Furthermore, underlying biological processes demonstrated in the radiomics model will offer valuable insights for guiding immunotherapy strategies. Key Points MVI is of prognostic significance in cHCC-CCA, but lacks reliable preoperative assessment. The MRI-based radiomics model predicts MVI status effectively in cHCC-CCA. The MRI-based radiomics model demonstrated prognostic value and underlying biological processes. The radiomics model could guide immunotherapy and risk stratification in cHCC-CCA. Graphical Abstract

Abstract. Background:. Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-naïve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-naïve MM. Methods:. This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM patients. Results:. A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-naïve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG+Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1)+ DCs, IFN-responding DCs, MHCII+ DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-naïve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that “don’t eat me”-related genes and IFN-induced genes increase in treatment-naïve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16+ monocytes/macrophages and expression level of CD16. Cell–cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-naïve MM patients. Conclusions:. Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

Abstract Background For women who have experienced recurrent pregnancy loss (RPL), it is crucial not only to treat them but also to evaluate the risk of recurrence. The study aimed to develop a risk predictive model to predict the subsequent early pregnancy loss (EPL) in women with RPL based on preconception data. Methods A prospective, dynamic population cohort study was carried out at the Second Hospital of Lanzhou University. From September 2019 to December 2022, a total of 1050 non-pregnant women with RPL were participated. By December 2023, 605 women had subsequent pregnancy outcomes and were randomly divided into training and validation group by 3:1 ratio. In the training group, univariable screening was performed on RPL patients with subsequent EPL outcome. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables, respectively. Subsequent EPL prediction model was constructed using generalize linear model (GLM), gradient boosting machine (GBM), random forest (RF), and deep learning (DP). The variables selected by LASSO regression and multivariate logistic regression were then established and compared using the best prediction model. The AUC, calibration curve, and decision curve (DCA) were performed to assess the prediction performances of the best model. The best model was validated using the validation group. Finally, a nomogram was established based on the best predictive features. Results In the training group, the GBM model achieved the best performance with the highest AUC (0.805). The AUC between the variables screened by the LASSO regression (16-variables) and logistic regression (9-variables) models showed no significant difference (AUC: 0.805 vs. 0.777, P = 0.1498). Meanwhile, the 9-variable model displayed a well discrimination performance in the validation group, with an AUC value of 0.781 (95%CI 0.702, 0.843). The DCA showed the model performed well and was feasible for making beneficial clinical decisions. Calibration curves revealed the goodness of fit between the predicted values by the model and the actual values, the Hosmer–Lemeshow test was 7.427, and P = 0.505. Conclusions Predicting subsequent EPL in RPL patients using the GBM model has important clinical implications. Future prospective studies are needed to verify the clinical applicability. Trial registration This study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020).

ABSTRACT: Milk coagulation is an important step in the production of fermented dairy products such as yogurt and cheese. Jujube is gaining popularity and acceptance as a food ingredient. In China, jujube yogurt is popular among consumers. However, there is limited information on the effect of jujube on acid- and rennet-induced coagulation properties of milk. The objective of this study was to evaluate the effects of jujube pulp at different concentrations on acid- and rennet-induced coagulation kinetics of milk and the microstructure of acid- and rennet-induced gels. During acid-induced coagulation, with increasing jujube pulp concentration, the initial pH value decreased; however, the final pH value increased. The initial elasticity index (EI) value increased, and the time point at which the mean square displacement curves lost the linear trend advanced. The sample with 10% jujube pulp had the densest structure and highest EI value. During rennet-induced coagulation, with increasing jujube pulp concentration, the production rate and amount of caseinomacropeptide decreased, and the final EI value increased. Protein aggregates in rennet-induced gels became rough, and the sample with 20% jujube pulp had the highest EI value. This study provides a new perspective and understanding of the application of jujube in fermented dairy products.

ObjectiveTo solve the problems of the fluctuating pressure and acoustic radiation of a cascade in turbulence, the theory of the cascade response function is introduced and analyzed. MethodsThe theory assumes that cascade blades have no thickness, and the integral expression of the cascade scattering field is solved by the Wiener−Hopf method, so that the analytical expression of the velocity potential of the cascade scattering field and the unsteady pressure coefficient of the cascade surface can be obtained, and the radiated sound power of the outer watershed of the cascade can be further obtained. The pressure coefficient and radiated sound power of the cascade are calculated by the analytical formula and compared with the results of the numerical method. The function is further extended to underwater, and the unsteady forces predicted by the cascade response function and Sears function are compared. ResultsThe results obtained by the analytical method and numerical method are consistent.The frequency spectrum curves of the cascade unsteady lift coefficient calculated by the cascade response function and Sears function have the same trend. ConclusionThe calculated results of the cascade response function are slightly lower than those of the Sears function in amplitude. However, compared with the cascade response function, the Sears function in a single wavenumber domain cannot take into account the effects of the placement angle, trim and sideslope on the unsteady lift of the cascade.

Abstract Background This study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes mellitus (GDM). Additionally, it sought to evaluate the interaction and joint association of Hb levels and Hp genotype with GDM risk. Methods This retrospective study involved 358 women with GDM and 1324 women with normal glucose tolerance (NGT). Peripheral blood leukocytes were collected from 360 individuals at 14–16 weeks’ gestation for Hp genotyping. GDM was diagnosed between 24–28 weeks’ gestation. Interactive moderating effect, joint analysis, and mediation analysis were performed to evaluate the crosslink of Hb levels and Hp genotype with GDM risk. Results Women who developed GDM had significantly higher Hb levels throughout pregnancy compared to those with NGT. Increase first-trimester Hb concentration was associated with a progressive rise in GDM incidence, glucose levels, glycosylated hemoglobin levels, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) values, cesarean delivery rates, and composite neonatal outcomes. Spline regression showed a significant linear association of GDM incidence with continuous first-trimester Hb level when the latter exceeded 122 g/L. Increased first-trimester Hb concentration was an independent risk factor for GDM development after adjusting for potential confounding factors in both the overall population and a matched case-control group. The Hp2–2 genotype was more prevalent among pregnant women with GDM when first-trimester Hb exceeded 122 g/L. Significant multiplicative and additive interactions were identified between Hb levels and Hp genotype for GDM risk, adjusted for age and pre-pregnancy BMI. The odds ratio (OR) for GDM development increased incrementally when stratified by Hb levels and Hp genotype. Moreover, first-trimester Hb level partially mediated the association between Hp genotype and GDM risk. Conclusion Increased first-trimester Hb levels were closely associated with the development of GDM and adverse pregnancy outcomes, with this association moderated by the Hp2–2 genotype.

Abstract Aims Surveys and research on the applications of the hepatic venous pressure gradient (HVPG) are important for understanding the current status and future development of this technology in China. This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022. Methods We investigated the overall status of HVPG technology in China—including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications, and current challenges by using online questionnaire. By counting the number and percentages of cases of these results, we hope to clarify the current status of HVPG measurements in China. Results According to the survey, 85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces. A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022, of which 2813 cases (56.4%) were measured alone. The average cost of HVPG measurement was 5646.8 ± 2327.9 CNY. Of the clinical teams who performed the measurements (sometimes multiple per hospital), 94.3% (82/87) used the balloon method, and the majority of the teams (72.4%, 63/87) used embolectomy catheters. Conclusions This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology. It is still necessary to continue promoting and popularizing this technology in the future.

Abstract Light intensity is a key factor affecting the synthesis of secondary metabolites in plants. However, the response mechanisms of metabolites and genes in Gentiana macrophylla under different light intensities have not been determined. In the present study, G. macrophylla seedlings were treated with LED light intensities of 15 µmol/m2/s (low light, LL), 90 µmol/m2/s (medium light, ML), and 200 µmol/m2/s (high light, HL), and leaves were collected on the 5th day for further investigation. A total of 2162 metabolites were detected, in which, the most abundant metabolites were identified as flavonoids, carbohydrates, terpenoids and amino acids. A total of 3313 and 613 differentially expressed genes (DEGs) were identified in the LL and HL groups compared with the ML group, respectively, mainly enriched in KEGG pathways such as carotenoid biosynthesis, carbon metabolism, glycolysis/gluconeogenesis, amino acids biosynthesis, plant MAPK pathway and plant hormone signaling. Besides, the transcription factors of GmMYB5 and GmbHLH20 were determined to be significantly correlated with loganic acid biosynthesis; the expression of photosystem-related enzyme genes was altered under different light intensities, regulating the expression of enzyme genes involved in the carotenoid, chlorophyll, glycolysis and amino acids pathway, then affecting their metabolic biosynthesis. As a result, low light inhibited photosynthesis, delayed glycolysis, thus, increased certain amino acids and decreased loganic acid production, while high light got an opposite trend. Our research contributed significantly to understand the molecular mechanism of light intensity in controlling metabolic accumulation in G. macrophylla.

Abstract Uncaria rhynchophylla is an important traditional herbal medicine in China, and the yield and quality of Uncaria rhynchophylla can be improved by suitable soil conditioners because of changing the soil properties. In this paper, Uncaria rhynchophylla associated alkaloids and soil microbial communities were investigated. The field experiment was set up with the following control group: (M1, no soil conditioner) and different soil conditioner treatment groups (M2, biomass ash; M3, water retention agent; M4, biochar; M5, lime powder and M6, malic acid). The results showed that M2 significantly increased the fresh and dry weight and the contents of isorhynchophylline, corynoxeine, isocorynoxeine, and total alkaloids. Acidobacteria, Proteobacteria, Actinobacteria, and Chloroflexi were major bacterial phyla. Correlation analysis showed that fresh and dry weight was significantly positively correlated with Acidobacteria, while alkali-hydrolyzable nitrogen, phosphatase activity, fresh and dry weight, corynoxeine, and isocorynoxeine were significantly negatively correlated with Chloroflexi. The application of soil conditioner M2 increased the abundance of Acidobacteria and decreased the abundance of Chloroflexi, which contributed to improving the soil nutrient content, yield, and quality of Uncaria rhynchophylla. In summary, biomass ash may be a better choice of soil conditioner in Uncaria rhynchophylla growing areas.

Abstract Background Multidrug resistance (MDR) limits successful cancer chemotherapy. P-glycoprotein (P-gp), BCRP and MRP1 are the key triggers of MDR. Unfortunately, no MDR modulator was approved by FDA to date. Here, we will investigate the effect of BI-2865, a pan-KRAS inhibitor, on reversing MDR induced by P-gp, BCRP and MRP1 in vitro and in vivo, and its reversal mechanisms will be explored. Methods The cytotoxicity of BI-2865 and its MDR removal effect in vitro were tested by MTT assays, and the corresponding reversal function in vivo was assessed through the P-gp mediated KBv200 xenografts in mice. BI-2865 induced alterations of drug discharge and reservation in cells were estimated by experiments of Flow cytometry with fluorescent doxorubicin, and the chemo-drug accumulation in xenografts’ tumor were analyzed through LC-MS. Mechanisms of BI-2865 inhibiting P-gp substrate’s efflux were analyzed through the vanadate-sensitive ATPase assay, [125I]-IAAP-photolabeling assay and computer molecular docking. The effects of BI-2865 on P-gp expression and KRAS-downstream signaling were detected via Western blotting, Flow cytometry and/or qRT-PCR. Subcellular localization of P-gp was visualized by Immunofluorescence. Results We found BI-2865 notably fortified response of P-gp-driven MDR cancer cells to the administration of chemo-drugs including paclitaxel, vincristine and doxorubicin, while such an effect was not observed in their parental sensitive cells and BCRP or MRP1-driven MDR cells. Importantly, the mice vivo combination study has verified that BI-2865 effectively improved the anti-tumor action of paclitaxel without toxic injury. In mechanism, BI-2865 prompted doxorubicin accumulating in carcinoma cells by directly blocking the efflux function of P-gp, which more specifically, was achieved by BI-2865 competitively binding to the drug-binding sites of P-gp. What’s more, at the effective MDR reversal concentrations, BI-2865 neither varied the expression and location of P-gp nor reduced its downstream AKT or ERK1/2 signaling activity. Conclusions This study uncovered a new application of BI-2865 as a MDR modulator, which might be used to effectively, safely and specifically improve chemotherapeutic efficacy in the clinical P-gp mediated MDR refractory cancers.

Abstract The early screening of depression is highly beneficial for patients to obtain better diagnosis and treatment. While the effectiveness of utilizing voice data for depression detection has been demonstrated, the issue of insufficient dataset size remains unresolved. Therefore, we propose an artificial intelligence method to effectively identify depression. The wav2vec 2.0 voice-based pre-training model was used as a feature extractor to automatically extract high-quality voice features from raw audio. Additionally, a small fine-tuning network was used as a classification model to output depression classification results. Subsequently, the proposed model was fine-tuned on the DAIC-WOZ dataset and achieved excellent classification results. Notably, the model demonstrated outstanding performance in binary classification, attaining an accuracy of 0.9649 and an RMSE of 0.1875 on the test set. Similarly, impressive results were obtained in multi-classification, with an accuracy of 0.9481 and an RMSE of 0.3810. The wav2vec 2.0 model was first used for depression recognition and showed strong generalization ability. The method is simple, practical, and applicable, which can assist doctors in the early screening of depression.

Abstract Human‐wildlife interactions become increasingly common in urban areas across all continents and ecosystem types. Depending on the context, human‐wildlife interactions can be categorized as harmonious, neutrality, or in conflict and raises cultural, economic and ecological challenges in maintaining urban biodiversity. Understanding the mechanism behind the tolerance of residents to the presence of wildlife is vital to promoting a harmonious coexistence between humans and wildlife in urban environments. To advance our knowledge of this mechanism, we developed a questionnaire to survey residents in Shanghai, China about their knowledge of and attitude towards raccoon dogs (Nyctereutes procyonoides), a species whose population is increasing in urban areas. Using 281 questionnaires, we conducted structural equation modelling to examine how relational values, including familiarity with raccoon dogs, perceived benefits and risks, together with residents' trust in wildlife management authorities, interactively influence the tolerance for this species. We found that the residents' familiarity with raccoon dogs positively influenced their tolerance, both directly and indirectly through increased perceived benefits and reduced perceived risks. Furthermore, trust in wildlife management authorities contributed to higher tolerance through perceived benefits. Our results suggested that education about the relational values of raccoon dogs to the public can reduce the traditional negative connotation for this species and promote the coexistence of people and raccoon dogs in Shanghai urban environment. Based on our understanding about how raccoon dogs were culturally constructed and the willingness of residents to share landscapes with the species, we advocate that relational values play an important role in future urban biodiversity conservation planning. We also advocate for education programs that familiarize the public with raccoon dogs as well as other species, which can turn urban human‐wildlife conflicts into harmonious relationships in Shanghai and other urban areas. Read the free Plain Language Summary for this article on the Journal blog.

Abstract This study aimed to identify factors that affect lymphovascular space invasion (LVSI) in endometrial cancer (EC) using machine learning technology, and to build a clinical risk assessment model based on these factors. Samples were collected from May 2017 to March 2022, including 312 EC patients who received treatment at Xuzhou Medical University Affiliated Hospital of Lianyungang. Of these, 219 cases were collected for the training group and 93 for the validation group. Clinical data and laboratory indicators were analyzed. Logistic regression and least absolute shrinkage and selection operator (LASSO) regression were used to analyze risk factors and construct risk models. The LVSI and non-LVSI groups showed statistical significance in clinical data and laboratory indicators (P

Objective: The present study aimed to explore the expression and clinical significance of human papilloma virus-related pathogenic factors (p16, cyclin D1, p53) in patients with head and neck squamous cell carcinoma (HNSCC) and construct a predictive model. Methods: The Cancer Genome Atlas was used to obtain clinical data for 112 patients with HNSCC. Expression of p16, p53, and cyclin D1 was quantified. We used the survival package of the R program to set the cut-off value. Values above the cut-off were considered positive, while values below the cut-off were negative. Kaplan–Meier analysis and univariate and multivariate Cox regression analyses were performed to investigate prognostic clinicopathological indicators and the expression of p16, p53, and cyclin D1. A predictive model was constructed based on the results of multifactor Cox regression analysis, and the accuracy of the predictive model was verified through final calibration analysis. Follow-up of patients with HNSCC at the Affiliated Hospital of Binzhou Medical University was conducted from 2015 to 2017, and reliability of the predictive model was validated based on follow-up data and molecular expression levels. Results: According to the results, expression of p16 and p53 was significantly associated with prognosis (P < .05). The predictive model constructed based on the expression levels of p16 and p53 was useful for evaluating the prognosis of patients with HNSCC. The predictive model was validated using follow-up data obtained from the hospital, and the trend of the follow-up results was consistent with the predictive model. Conclusion: p16 and p53 can be used as key indicators to predict the prognosis of HNSCC patients and as critical immunohistochemical indicators in clinical practice. The survival model constructed based on p16 and p53 expression levels reliably predicts patient prognosis.

Thermochemical conversions are pathways for biomass utilization to produce various value-added energy and chemical products. For the development of novel thermochemical conversion technologies, an accurate understanding of the reaction performance and kinetics is essential. Given the diversity of the thermal analysis techniques, it is necessary to understand the features and limitations of the reactors, ensuring that the selected thermal analysis reactor meets the specific need for reaction characterization. This paper provides a critical overview of the thermal analysis reactors based on the following perspectives: 1) gas flow conditions in the reactor, 2) particle's external and internal heat and mass transfer limitations, 3) heating rate, 4) temperature distribution, 5) nascent char production and reaction, 6) liquid feeding and atomization, 7) simultaneous sampling and analyzing of bed materials, and 8) reacting atmosphere change. Finally, prospects and future research directions in the development of analysis techniques are proposed.

An additive manufacturing technology was used to produce anode foils with different polystyrene microsphere (PSM). The effect of PSM addition in the range of 0–20 vol% on the specific capacitance and bending strength of the anode foils was investigated. Scanning electron microscopy analysis confirms the presence of pores in the anode foils, which is attributed to the addition of PSM. The porosity and pore diameter of the anode foils increase with increasing PSM content, resulting in an initial increase and then a decrease in specific capacitance, as well as a gradual increase in bending strength. At a PSM addition of 12.5 vol%, the anode foils exhibit a high specific capacitance of 0.927 μF/cm2 and a bending strength of over 120 times greater, meeting the specific capacitance and bending strength requirements for anode foils in aluminum electrolytic capacitors. These findings suggest that incorporating PSM into anode foils is an effective method for adjusting their specific capacitance and bending strength.

Abstract Introduction The management of erythrodermic psoriasis (EP), a rare but severe type of psoriasis, is challenging, especially in patients with concomitant chronic hepatitis B (CHB). We previously demonstrated that oxymatrine treatment alleviated severe plaque psoriasis, but its therapeutic potential in treating EP remains unexplored. This study was to assess the efficacy and safety of oxymatrine for the treatment of EP, with attention to concomitant CHB. Methods In this investigator-initiated clinical trial, four consecutive patients with EP, including two (A and B) with concomitant CHB, were treated with intravenous administration of oxymatrine as monotherapy for 8 weeks, and scheduled to be followed up for a minimum of 24 weeks. The primary outcome was at least 75% improvement in the psoriasis area and severity index (PASI 75) at week 32. Secondary outcomes included the body surface area (BSA) score, dermatology life quality index (DLQI)], and safety. Results Patients A, B, and C achieved PASI 75 at treatment completion and week 32, demonstrating improvements of 77.4%, 97.2%, and 100% in PASI, respectively. Their BSA and DLQI were also improved significantly at week 32 and throughout follow-up of 37, 57, and 105 weeks, respectively. The viral loads in patients A and B with CHB decreased modestly. Patient D discontinued after follow-up for 19 weeks, and the primary outcome could not be analyzed. No adverse events were reported during treatment and follow-up. Conclusion Oxymatrine appears to be efficacious and safe for the treatment of patients with EP, including those with concomitant CHB. Trial Registration This study was registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ; Registration number ChiCTR-TRC-14004301).

Warburgia ugandensis and Saururus chinensis are two of the most important medicinal plants in magnoliids and are widely utilized in traditional Kenya and Chinese medicine, respectively. The absence of higher-quality reference genomes has hindered research on the medicinal compound biosynthesis mechanisms of these plants. We report the chromosome-level genome assemblies of W. ugandensis and S. chinensis, and generated 1.13 Gb and 0.53 Gb genomes from 74 and 27 scaffolds, respectively, using BGI-DIPSEQ, Nanopore, and Hi-C sequencing. The scaffold N50 lengths were 82.97 Mb and 48.53 Mb, and the assemblies were anchored to 14 and 11 chromosomes of W. ugandensis and S. chinensis, respectively. In total, 24,739 and 20,561 genes were annotated, and 98.5% and 98% of the BUSCO genes were fully represented, respectively. The chromosome-level genomes of W. ugandensis and S. chinensis will be valuable resources for understanding the genetics of these medicinal plants, studying the evolution of magnoliids and angiosperms and conserving plant genetic resources.

Abstract Cancer cells undergo metabolic reprogramming in response to hostile microenvironments, such as energy stress; however, the underlying mechanisms remain largely unclear. It is also unknown whether energy stress-responsive circular RNA (circRNA) is involved in the regulation of glucose metabolism. Here we report that circDDX21 is upregulated in response to glucose deprivation by the transcription factor c-Myc. Functionally, circDDX21 is shown to promote glycolysis by increasing PGAM1 expression. Mechanistically, circDDX21 interacts with the RNA binding protein PABPC1, disrupting its association with the ubiquitin E3 ligase MKRN3. This disassociation attenuates MKRN3-mediated PABPC1 ubiquitination and enhances the binding of PABPC1 to PGAM1 mRNA, thereby leading to PGAM1 mRNA stabilization. The ability of the circDDX21-PGAM1 axis to promote hepatocellular carcinogenesis is validated in a xenograft mouse model. Additionally, in clinical hepatocellular carcinoma tissues, there is a positive correlation between circDDX21 and PGAM1 expression. These findings establish circDDX21 as an important regulator of glycolysis and suggest circDDX21 as a potential therapeutic target for hepatocellular carcinoma.

Abstract Background This study aims to assess the long-term trends in the burden of three major gynecologic cancers(GCs) stratified by social-demographic status across the world from 1990 to 2019. To assess the trends of risk factor attributed mortality, and to examine the specific effects of age, period, cohort behind them in different regions. Methods We extracted data on the mortality, disability-adjusted life years(DALYs), and age-standardized rates(ASRs) of cervical cancer(CC), uterine cancer(UC), and ovarian cancer(OC) related to risks from 1990 to 2019, as GCs burden measures. Age-period-cohort analysis was used to analyze trends in attributable mortality rates. Results The number of deaths and DALYs for CC, UC and OC increased since 1990 worldwide, while the ASDRs decreased. Regionally, the ASDR of CC was the highest in low SDI region at 15.05(11.92, 18.46) per 100,000 in 2019, while the ASDRs of UC and OC were highest in high SDI region at 2.52(2.32,2.64), and 5.67(5.16,6.09). The risk of CC death caused by unsafe sex increased with age and then gradually stabilized, with regional differences. The period effect of CC death attributed to smoking showed a downward trend. The cohort effect of UC death attributed to high BMI decreased in each region, especially in the early period in middle, low-middle and low SDI areas. Conclusions Global secular trends of attributed mortality for the three GCs and their age, period, and cohort effects may reflect the diagnosis and treatment progress, rapid socioeconomic transitions, concomitant changes in lifestyle and behavioral patterns in different developing regions. Prevention and controllable measures should be carried out according to the epidemic status in different countries, raising awareness of risk factors to reduce future burden.