Molecular-Sieving Separation of Methanol/Benzene Azeotrope by a Flexible Metal-Organic Framework.

Separation of methanol/benzene azeotrope mixtures is very challenging not only by the conventional distillation technique but also by adsorbents. In this work, we design and synthesize a flexible Ca-based metal-organic framework MAF-58 consisting of cheap raw materials. MAF-58 shows selective methanol-induced pore-opening flexibility. Although the opened pores are large enough to accommodate benzene molecules, MAF-58 shows methanol/benzene molecular sieving with ultrahigh experimental selectivity, giving 5.1 mmol g-1 high-purity (99.99%+) methanol and 2.0 mmol g-1 high-purity (99.97%+) benzene in a single adsorption/desorption cycle. Computational simulations reveal that the preferentially adsorbed, coordinated methanol molecules act as the gating component to selectively block the diffusion of benzene, offering a new gating adsorption mechanism.

Minimal residual disease profiling predicts pathological complete response in esophageal squamous cell carcinoma.

Accurate presurgical prediction of pathological complete response (pCR) can guide treatment decisions, potentially avoiding unnecessary surgeries and improving the quality of life for cancer patients. We developed a minimal residual disease (MRD) profiling approach with enhanced sensitivity and specificity for detecting minimal tumor DNA from cell-free DNA (cfDNA). The approach was validated in two independent esophageal squamous cell carcinoma (ESCC) cohorts. In a cohort undergoing neoadjuvant, surgical, and adjuvant therapy (NAT cohort), presurgical MRD status precisely predicted pCR. All MRD-negative cases (10/10) were confirmed as pCR by pathological evaluation on the resected tissues. In contrast, MRD-positive cases included all the 27 non-pCR cases and only one pCR case (10/10 vs 1/28, P < 0.0001, Fisher's exact test). In a definitive radiotherapy cohort (dRT cohort), post-dRT MRD status was closely correlated with patient prognosis. All MRD-negative patients (25/25) remained progression-free during the follow-up period, while 23 of the 26 MRD-positive patients experienced disease progression (25/25 vs 3/26, P < 0.0001, Fisher's exact test; progression-free survival, P < 0.0001, log-rank test). The MRD profiling approach effectively predicted the ESCC patients who would achieve pCR with surgery and those likely to remain progression-free without surgery. This suggests that the cancer cells in these MRD-negative patients have been effectively eliminated and they could be suitable candidates for a watch-and-wait strategy, potentially avoiding unnecessary surgery.

In Situ Photogenerated Radicals of Hydroxyl Substituted Pyrene-Based Triphenylamines with Enhanced Transport and Free Doping/Post-Oxidation for Efficient Perovskite Solar Cells.

The high-performance hole transporting material (HTM) is one of the most important components for the perovskite solar cells (PSCs) in promoting power conversion efficiency (PCE). However, the low conductivity of HTMs and their additional requirements for doping and post-oxidation greatly limits the device performance. In this work, three novel pyrene-based derivatives containing methoxy-substituted triphenylamines units (PyTPA, PyTPA-OH and PyTPA-2OH) are designed and synthesized, where different numbers of hydroxyl groups are connected at the 2- or 2,7-positions of the pyrene core. These hydroxyl groups at the 2- or 2,7-positions of pyrene play a significantly role to enhance the intermolecular interactions that are able to generate in situ radicals with the assistance of visible light irradiation, resulting in enhanced hole transferring ability, as well as an enhanced conductivity and suppressed recombination. These pyrene-core based HTMs exhibit excellent performance in PSCs, which possess a higher PCE than those control devices using the traditional spiro-OMeTAD as the HTM. The best performance can be found in the devices with PyTPA-2OH. It has an average PCE of 23.44% (PCEmax = 23.50%), which is the highest PCE among the reported PSCs with the pyrene-core based HTMs up to date. This research offers a novel avenue to design a dopant-free HTM by the combination of the pyrene core, methoxy triphenylamines, and hydroxy groups.

The RALF2-FERONIA-MYB63 module orchestrates growth and defense in tomato roots.

Plant secreted peptides RAPID ALKALINISATION FACTORs (RALFs), which act through the receptor FERONIA (FER), play important roles in plant growth. However, it remains unclear whether and how RALF-FER contributes to the trade-off of plant growth-defense. Here, we used a variety of techniques such as CRISPR/Cas9, protein-protein interaction and transcriptional regulation methods to investigate the role of RALF2 and its receptor FER in regulating lignin deposition, root growth, and defense against Fusarium oxysporum f. sp. lycopersici (Fol) in tomato (Solanum lycopersicum). The ralf2 and fer mutants show reduced primary root length, elevated lignin accumulation, and enhanced resistance against Fol than the wild-type. FER interacts with and phosphorylates MYB63 to promote its degradation. MYB63 serves as an activator of lignin deposition by regulating the transcription of dirigent protein gene DIR19. Mutation of DIR19 suppresses lignin accumulation, and reverses the short root phenotype and Fol resistance in ralf2 or fer mutant. Collectively, our results demonstrate that the RALF2-FER-MYB63 module fine-tunes root growth and resistance against Fol through regulating the deposition of lignin in tomato roots. The study sheds new light on how plants maintain the growth-defense balance via RALF-FER.

New strategies to study in depth the metabolic mechanism of astaxanthin biosynthesis in Phaffia rhodozyma.

Astaxanthin, a ketone carotenoid known for its high antioxidant activity, holds significant potential for application in nutraceuticals, aquaculture, and cosmetics. The increasing market demand necessitates a higher production of astaxanthin using Phaffia rhodozyma. Despite extensive research efforts focused on optimizing fermentation conditions, employing mutagenesis treatments, and utilizing genetic engineering technologies to enhance astaxanthin yield in P. rhodozyma, progress in this area remains limited. This review provides a comprehensive summary of the current understanding of rough metabolic pathways, regulatory mechanisms, and preliminary strategies for enhancing astaxanthin yield. However, further investigation is required to fully comprehend the intricate and essential metabolic regulation mechanism underlying astaxanthin synthesis. Specifically, the specific functions of key genes, such as crtYB, crtS, and crtI, need to be explored in detail. Additionally, a thorough understanding of the action mechanism of bifunctional enzymes and alternative splicing products is imperative. Lastly, the regulation of metabolic flux must be thoroughly investigated to reveal the complete pathway of astaxanthin synthesis. To obtain an in-depth mechanism and improve the yield of astaxanthin, this review proposes some frontier methods, including: omics, genome editing, protein structure-activity analysis, and synthetic biology. Moreover, it further elucidates the feasibility of new strategies using these advanced methods in various effectively combined ways to resolve these problems mentioned above. This review provides theory and method for studying the metabolic pathway of astaxanthin in P. rhodozyma and the industrial improvement of astaxanthin, and provides new insights into the flexible combined use of multiple modern advanced biotechnologies.

Ferroptosis: a promising candidate for exosome-mediated regulation in different diseases.

Ferroptosis is a newly discovered form of cell death that is featured in a wide range of diseases. Exosome therapy is a promising therapeutic option that has attracted much attention due to its low immunogenicity, low toxicity, and ability to penetrate biological barriers. In addition, emerging evidence indicates that exosomes possess the ability to modulate the progression of diverse diseases by regulating ferroptosis in damaged cells. Hence, the mechanism by which cell-derived and noncellular-derived exosomes target ferroptosis in different diseases through the system Xc-/GSH/GPX4 axis, NAD(P)H/FSP1/CoQ10 axis, iron metabolism pathway and lipid metabolism pathway associated with ferroptosis, as well as its applications in liver disease, neurological diseases, lung injury, heart injury, cancer and other diseases, are summarized here. Additionally, the role of exosome-regulated ferroptosis as an emerging repair mechanism for damaged tissues and cells is also discussed, and this is expected to be a promising treatment direction for various diseases in the future. Video Abstract.

Genome-wide characterization of cytochrome P450 genes reveals the potential roles in fruit ripening and response to cold stress in tomato.

Plant cytochrome P450 (CYP) superfamily, the largest enzyme metabolism family, has been identified in many species and plays a vital role in plant development and stress response via secondary metabolite biosynthesis. A comprehensive identification and functional investigation of CYPs in tomato plants would contribute to deeper understanding of their biological significance. In this study, 268 tomato CYP genes were identified and found to be unevenly located on 12 chromosomes. Based on the phylogenetic analysis, these 268 SlCYPs were classed into two distinct clades (A-type and non-A-type) and nine clans, including 48 families. Moreover, 67 tandem and 22 WGD (whole genome duplication)/segmental duplication events were detected, of which 12 SlCYP genes experienced both WGD/segmental and tandem duplication events, indicating that tandem duplication plays a major role in the expansion of the SlCYP family. Besides, 48 pairs containing 41 SlCYP and 44 AtCYP genes were orthologous, while 216 orthologous pairs were obtained between tomato and potato. The expression level of all SlCYP genes in tomato tissues at different development stages was analyzed, and most expressed SlCYPs showed a tissue-specific pattern. Meanwhile, 143 differentially expressed SlCYPs were identified under cold stress. Furthermore, the RT-qPCR results indicated that SlCYPs may be involved in fruit ripening and cold tolerance in tomato seedlings. These findings provide valuable insights into the evolutionary relationships and functional characteristics of SlCYPs, which can be utilized for further investigation of fruit metabolic pathways and cold tolerance in tomato.

Multicenter phase II study of moderate low-dose radiotherapy in indolent non-Hodgkin lymphoma: CLCG-iNHL-01 protocol.

Background: Radiotherapy is an effective treatment for indolent non-Hodgkin lymphoma (iNHL); however, the optimal radiotherapy dose remains to be determined. We hypothesize that a suitable dose may exist between 4 and 24 Gy. Methods: This prospective multicenter phase II trial intends to recruit 73 sites of iNHL patients, who will receive involved-site radiotherapy of 12 Gy in four fractions. The primary objective is the 6-month clinical complete response rate. Tumor tissue, blood and conjunctival specimens will be collected to identify potential predictive biomarkers. Discussion: The CLCG-iNHL-01 trial will evaluate the efficacy and toxicity of 12 Gy in patients with iNHL and provide information on a novel hypofractionation regimen of low-dose radiotherapy. Clinical Trial Registration: NCT05543070 (ClinicalTrials.gov).

A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity.

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics.

Impact of pre-delivery medication treatment on delivery outcome in patients with primary immune thrombocytopenia: a cohort study.

BACKGROUND: Clinical research data showed a series of adverse events in the delivery period of primary immune thrombocytopenia (ITP) patients, including high cesarean section rate. Consensus report proposed that for patients with platelet count below 50 × 109/L, prednisone or intravenous immunoglobulins (IVIg) can be given to raise the platelet count in third trimester in preparation for labor. OBJECTIVES: To evaluate the effect of low-dose prednisone or IVIg therapy on delivery outcomes in patients with ITP. STUDY DESIGN: This was a cohort study that included pregnant women with ITP from January 2017 to December 2022. Patients with platelet counts of (20-50) ×109/L at the time of delivery (≥34 weeks) and who had not received any medication before were enrolled in the study. Patients were divided into the pre-delivery medication group (oral prednisone or IVIg) and untreated group according to their preferences. The differences in vaginal delivery rate, postpartum bleeding rate, and platelet transfusion volume between the two groups were compared using t-test, Wilcoxon rank-sum test, and χ2 test. Logistic regression analysis was used to identify the factors affecting vaginal delivery rate and postpartum bleeding rate, and multiple linear regression analysis was used to identify the factors affecting platelet transfusion volume. RESULTS: During the study period, a total of 96 patients with ITP were enrolled, including 70 in the pre-delivery medication group and 26 in the untreated group. The platelet count of pre-delivery medication group was 54.8 ± 34.5 × 109/L, which was significantly higher than that of untreated group 34.4 ± 9.0 × 109/L (p = .004). The vaginal delivery rate of the medication group was higher than the untreated group [60.0% (42/70) vs. 30.8% (8/26), χ2 = 6.49, p = .013]. After adjusting for the proportion of multiparous women and gestational weeks, the results showed that medication therapy during the peripartum period was associated with vaginal delivery (OR = 4.937, 95% CI: 1.511-16.136, p = .008). The postpartum bleeding rates were 22.9% (16/70) and 26.9% (7/26) in the medication group and untreated group, respectively, with no significant difference between the two groups (χ2 = 0.17, p = .789), while the platelet transfusion volume was lower in the medication group than untreated group [(1.1 ± 1.0) vs. (1.6 ± 0.8) U]. CONCLUSION: Pre-delivery medication therapy can increase vaginal delivery rate, reduce platelet transfusion volume, but does not decrease the incidence of postpartum hemorrhage.

What is the context?The high cesarean section rate has always been a prominent pregnancy issue in ITP patients. The data shows that the reason for cesarean section in most ITP patients may be related to early induced labor due to thrombocytopenia or patients' concerns of bleeding events during delivery. The study of treatment during the perinatal period is expected to further increase platelet count and prepare for safer delivery.What is new?To date, no study has focused on pre-delivery treatment for pregnant ITP patients. In this study, patients with a platelet count<50 × 109/L after 34 weeks can experience a significant increase in platelet count after receiving immunoglobulin or prednisone therapy. The results of this study preliminarily demonstrate IVIg or prednisone is a promising pre-delivery treatment for pregnant ITP patients in preparation for labor. The pre-delivery medication therapy can improve the rate of successful vaginal delivery and reduce the consumption of blood products.What is the impact?This study provides further evidence that the target threshold for platelets should be raised in late third trimester, with a platelet count above 50 × 109/L as the standard for delivery, in order to further reduce the cesarean section rate and blood product infusion in ITP patients.

Exploring the causal connection: insights into diabetic nephropathy and gut microbiota from whole-genome sequencing databases.

Over recent years, the prevalence of diabetes has been on the rise, paralleling improvements in living standards. Diabetic nephropathy (DN), a prevalent complication of diabetes, has also exhibited a growing incidence. While some clinical studies and reviews have hinted at a link between diabetic nephropathy and gut microbiota (GM), the nature of this connection, specifically its causative nature, remains uncertain. Investigating the causal relationship between diabetic nephropathy and gut microbiota holds the promise of aiding in disease screening and identifying novel biomarkers. In this study, we employed a two-sample Mendelian randomization analysis. Our dataset encompassed 4,111 DN patients from the GWAS database, juxtaposed with 308,539 members forming a control group. The aim was to pinpoint specific categories within the vast spectrum of the 211 known gut microbiota types that may have a direct causal relationship with diabetic nephropathy. Rigorous measures, including extensive heterogeneity and sensitivity analyses, were implemented to mitigate the influence of confounding variables on our experimental outcomes. Ultimately, our comprehensive analysis revealed 15 distinct categories of gut microbiota that exhibit a causal association with diabetic nephropathy. In summary, the phyla Bacteroidota and Verrucomicrobiae, the families Peptostreptococcaceae and Veillonellaceae, the genus Akkermansia, and the species Catenibacterium, Lachnoclostridium, Parasutterella, along with the orders Bacteroidales and Verrucomicrobiales, and the class Bacteroidetes were identified as correlates of increased risk for DN. Conversely, the family Victivallaceae, the species Eubacterium coprostanoligenes, and the Clostridium sensu stricto 1 group were found to be associated with a protective effect against the development of DN.These findings not only provide valuable insights but also open up novel avenues for clinical research, offering fresh directions for potential treatments.

A Self-Powered Lactate Sensor Based on the Piezoelectric Effect for Assessing Tumor Development.

The build-up of lactate in solid tumors stands as a crucial and early occurrence in malignancy development, and the concentration of lactate in the tumor microenvironment may be a more sensitive indicator for analyzing primary tumors. In this study, we designed a self-powered lactate sensor for the rapid analysis of tumor samples, utilizing the coupling between the piezoelectric effect and enzymatic reaction. This lactate sensor is fabricated using a ZnO nanowire array modified with lactate oxidase (LOx). The sensing process does not require an external power source or batteries. The device can directly output electric signals containing lactate concentration information when subjected to external forces. The lactate concentration detection upper limit of the sensor is at least 27 mM, with a limit of detection (LOD) of approximately 1.3 mM and a response time of around 10 s. This study innovatively applied self-powered technology to the in situ detection of the tumor microenvironment and used the results to estimate the growth period of the primary tumor. The availability of this application has been confirmed through biological experiments. Furthermore, the sensor data generated by the device offer valuable insights for evaluating the likelihood of remote tumor metastasis. This study may expand the research scope of self-powered technology in the field of medical diagnosis and offer a novel perspective on cancer diagnosis.

Tumor-Derived Exosomal miR-143-3p Induces Macrophage M2 Polarization to Cause Radiation Resistance in Locally Advanced Esophageal Squamous Cell Carcinoma.

We aimed to determine whether monitoring tumor-derived exosomal microRNAs (miRNAs) could be used to assess radiotherapeutic sensitivity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). RNA sequencing was employed to conduct a comparative analysis of miRNA expression levels during radiotherapy, focusing on identifying miRNAs associated with progression. Electron microscopy confirmed the existence of exosomes, and co-cultivation assays and immunofluorescence validated their capacity to infiltrate macrophages. To determine the mechanism by which exosomal miR-143-3p regulates the interplay between ESCC cells and M2 macrophages, ESCC cell-derived exosomes were co-cultured with macrophages. Serum miR-143-3p and miR-223-3p were elevated during radiotherapy, suggesting resistance to radiation and an unfavorable prognosis for ESCC. Increased levels of both miRNAs independently predicted shorter progression-free survival (p = 0.015). We developed a diagnostic model for ESCC using serum microRNAs, resulting in an area under the curve of 0.751. Radiotherapy enhanced the release of miR-143-3p from ESCC cell-derived exosomes. Immune cell infiltration analysis at the Cancer Genome Atlas (TCGA) database revealed that ESCC cell-derived miR-143-3p triggered M2 macrophage polarization. Mechanistically, miR-143-3p upregulation affected chemokine activity and cytokine signaling pathways. Furthermore, ESCC cell exosomal miR-143-3p could be transferred to macrophages, thereby promoting their polarization. Serum miR-143-3p and miR-223-3p could represent diagnostic and prognostic markers for patients with ESCC undergoing radiotherapy. Unfavorable prognosis could be linked to the increased levels of ESCC cell-derived exosomal miR-143-3p, which might promote tumor progression by interacting with macrophages.

Reverse Separation of Carbon Dioxide and Acetylene in Two Isostructural Copper Pyridine-Carboxylate Frameworks.

Separating acetylene from carbon dioxide is important but highly challenging due to their similar molecular shapes and physical properties. Adsorptive separation of carbon dioxide from acetylene can directly produce pure acetylene but is hardly realized because of relatively polarizable acetylene binds more strongly. Here, we reverse the CO2 and C2H2 separation by adjusting the pore structures in two isoreticular ultramicroporous metal-organic frameworks (MOFs). Under ambient conditions, copper isonicotinate (Cu(ina)2), with relatively large pore channels shows C2H2-selective adsorption with a C2H2/CO2 selectivity of 3.4, whereas its smaller-pore analogue, copper quinoline-5-carboxylate (Cu(Qc)2) shows an inverse CO2/C2H2 selectivity of 5.6. Cu(Qc)2 shows compact pore space that well matches the optimal orientation of CO2 but is not compatible for C2H2. Neutron powder diffraction experiments confirmed that CO2 molecules adopt preferential orientation along the pore channels during adsorption binding, whereas C2H2 molecules bind in an opposite fashion with distorted configurations due to their opposite quadrupole moments. Dynamic breakthrough experiments have validated the separation performance of Cu(Qc)2 for CO2/C2H2 separation.

Our journey of developing multifunctional metal-organic frameworks.

Metal-organic frameworks (MOFs) are organic-inorganic hybrid solids constructed from the coordination interaction of metal ions/clusters with organic linkers, which currently represent one of the most rapidly expanding platforms for new functional materials. Based on well-established approaches, involving tuning the pore sizes, incorporation of functional sites and post-synthetic modification, the pore structures of MOFs can be readily controlled for multifunctional applications. In this brief review, we summarize and highlight our research progresses during our journey on developing functional MOFs for various applications including gas storage, gas separations, luminescent sensing, proton conduction, and molecular recognitions.

Pharmacological Interventions for Menière's Disease: A Systematic Review and Network Meta-Analysis.

Objective: Evaluation of the effectiveness and posttreatment effects of intratympanic gentamicin and corticosteroids in treating patients with Ménière's disease (MD). Methods: Based on PubMed and Embase databases, randomized controlled trials using intratympanic injections of 4 drugs (gentamicin, methylprednisolone, dexamethasone, and placebo) for the treatment of MD were searched from 1995 to October 2023, and the literature was screened according to inclusion and exclusion criteria, and data were netted for meta-analysis using Stata 17. Results: A total of 13 studies were selected, involving 559 participants, with follow-up time ranging from 3 to 28 months. Meta-analysis showed that there was no statistically significant difference in pure-tone average between gentamicin and dexamethasone [standardized mean difference (SMD) = 0.09, 95% confidence interval (CI) (-0.42, 0.24), P < .05]. Compared to placebo, intratympanic injection of gentamicin [risk ratio (RR) = 1.18, 95% CI (0.43, 1.93)], methylprednisolone [RR = 0.88, 95% CI (0.07, 1.70)], and dexamethasone [RR = 0.70, 95% CI (-0.01, 1.41)] all showed better efficacy in treating vertigo. For the treatment of tinnitus, the SUCRA ranking results showed that dexamethasone was the most effective, followed by methylprednisolone and gentamicin. Conclusion: Pharmacological intervention is more effective than placebo in treating MD. Although gentamicin treatment shows significant effects in treating vertigo, corticosteroid combination therapy is markedly superior to gentamicin in controlling hearing loss and vertigo symptoms.

Fixed-point algorithms for solving the critical value and upper tail quantile of Kuiper's statistics.

Kuiper's statistic is a good measure for the difference of ideal distribution and empirical distribution in the goodness-of-fit test. However, it is a challenging problem to solve the critical value and upper tail quantile, or simply Kuiper pair, of Kuiper's statistics due to the difficulties of solving the nonlinear equation and reasonable approximation of infinite series. In this work, the contributions lie in three perspectives: firstly, the second order approximation for the infinite series of the cumulative distribution of the critical value is used to achieve higher precision; secondly, the principles and fixed-point algorithms for solving the Kuiper pair are presented with details; finally, finally, a mistake about the critical value cnα for (α,n)=(0.01,30) in Kuiper's distribution table has been labeled and corrected where n is the sample capacity and α is the upper tail quantile. The algorithms are verified and validated by comparing with the table provided by Kuiper. The methods and algorithms proposed are enlightening and worth of introducing to the college students, computer programmers, engineers, experimental psychologists and so on.

Identification of Circulating Inflammatory Proteins Associated with Calcific Aortic Valve Stenosis by Multiplex Analysis.

Calcific aortic valve stenosis (CAVS) is characterized by increasing inflammation and progressive calcification in the aortic valve leaflets and is a major cause of death in the aging population. This study aimed to identify the inflammatory proteins involved in CAVS and provide potential therapeutic targets. We investigated the observational and causal associations of 92 inflammatory proteins, which were measured using affinity-based proteomic assays. Firstly, the case-control cohort identified differential proteins associated with the occurrence and progression of CAVS. Subsequently, we delved into exploring the causal impacts of these associated proteins through Mendelian randomization. This involved utilizing genetic instruments derived from cis-protein quantitative loci identified in genome-wide association studies, encompassing a cohort of over 400,000 individuals. Finally, we investigated the gene transcription and protein expression levels of inflammatory proteins by single-cell and immunohistochemistry analysis. Multivariate logistic regression and spearman's correlation analysis showed that five proteins showed a significant positive correlation with disease severity. Mendelian randomization showed that elevated levels of two proteins, namely, matrix metallopeptidase-1 (MMP1) and sirtuin 2 (SIRT2), were associated with an increased risk of CAVS. Immunohistochemistry and single-cell transcriptomes showed that expression levels of MMP1 and SIRT2 at the tissue and cell levels were significantly higher in calcified valves than in non-calcified control valves. These findings indicate that MMP1 and SIRT2 are causally related to CAVS and open up the possibility for identifying novel therapeutic targets.

Preoperative Planning of Lumbar Lordosis for Adult Degenerative Scoliosis Surgery in the Chinese Population.

OBJECTIVE: Pelvic incidence minus lumbar lordosis mismatch (PI-LL) is directly related to poor quality of life in adult degenerative scoliosis (ADS) patients. The purpose of the study was to determine the most appropriate postoperative PI-LL value for patients with ADS. METHODS: The medical records of patients with ADS in our department were retrospectively collected. The data included age, sex, body mass index, age-adjusted Charlson comorbidity index, osteopenia, length of hospital stay, operative duration, estimated blood loss, American Society of Anaesthesiologists score, number of fusion levels, lumbar lordosis, sagittal vertical axis, pelvic incidence, PI-LL, SRS-22 score, ODI score, and mechanical complications. RESULTS: A total of 316 patients were enrolled. PI-LL, lumbar lordosis, sagittal vertical axis, SRS-22 score, ODI score at the time of last follow-up were 20.7±8.5°, 23.4±14.1°, 4.0±2.1 cm, 3.7±0.9, and 18.1±5.5, respectively. In terms of mechanical complications, 88 patients (27.8%), 34 patients (10.8%), and 19 patients (6.0%) had proximal junctional kyphosis, distal junctional kyphosis, and implant-related complications, respectively. In the fully adjusted model, compared with 0 grade PI-LL group and ++ grade PI-LL group, + grade PI-LL group had the best clinical outcomes and the fewest mechanical complications. The stability of these conclusions was verified in sensitivity analyses. CONCLUSIONS: Optimal PI-LL value should be 10°-20° after corrective surgery in patients with adult degenerative scoliosis, which is associated with excellent clinical outcomes and lower complication rates. Previous criteria may be at risk of overcorrection, which may lead to proximal junctional kyphosis.

Seasonal changes in hepatic lipid metabolism and apoptosis in Chinese soft-shelled turtle (Pelodiscus sinensis).

Chinese soft-shelled turtle (Pelodiscus sinensis) hibernates without eating and drinking when the ambient temperature is very low. To better understand the characteristics of energy utilization during hibernation, the turtles in the physiological phases of summer active (SA), Pre-Hibernation (Pre-H), Mid-Hibernation (Mid-H) and early arousal (EA) were sampled. The results showed that the levels of serum triglyceride and hepatic lipid droplet were markedly increased in Pre-H and decreased in Mid-H compared with that in SA, indicating that P. sinensis experiences lipid accumulation in Pre-H and lipid is the predominant energy reserve during hibernation. The mRNA expression levels of genes (FABP and CPT-2) involved in lipolysis and lipid oxidation were up-regulated in Mid-H, while the genes related to lipid synthesis (FAS, ACSL-1, ACC, elovl5, and SCD1) were inhibited in Mid-H. Meanwhile, the mRNA expression levels of endoplasmic reticulum stress marker gene Bip and key genes (ATF4, ATF6, and IRE1α) involving the unfolded protein response were significantly increased in Mid-H and EA. Also, the expression levels of genes (ASK1, JNK1, and Bax) associated with cell apoptosis increased in Mid-H and EA, however, the expression of Bcl2 was inhibited in Mid-H. Therefore, hibernation can cause endoplasmic reticulum stress and apoptosis. The findings will provide a theoretical framework for an animal's cold adaptation and offer insights into preventing and managing metabolic syndrome.