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BACKGROUND: Postoperative delirium (POD) is a common complication following cardiac surgery and increases postoperative morbidity and mortality. Intraoperative electroencephalogram (EEG) burst suppression suggests excessively deep anesthesia and predicts POD. Use of remimazolam provides a stable hemodynamic status and an appropriate depth of anesthesia. We aim to assess remimazolam administered for anesthesia and sedation in elderly patients having cardiac surgery. METHODS: This is a randomized controlled clinical trial with noninferiority design. A total of 260 elderly patients aged equal to or greater than 60 years undergoing cardiac surgery will be randomly allocated to receive remimazolam or propofol (1:1) for general anesthesia and postoperative sedation until extubation. The primary outcome is the cumulative time with EEG burst suppression which is obtained from the SedLine system. The noninferiority margin is 2.0 min. The secondary outcomes include the POD occurrence within the first 5 days postoperatively and the duration of perioperative hypotension. DISCUSSION: This noninferiority trial is the first to evaluate the effect of perioperative remimazolam administration on EEG burst suppression, POD occurrence, and duration of hypotension in elderly patients who undergo cardiac surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200056353).

Abstract Background Small cell lung carcinoma (SCLC) is characterized by -poor prognosis, -high predilection for -metastasis, -proliferation, and -absence of newer therapeutic options. Elucidation of newer pathways characterizing the disease may allow for development of targeted therapies and consequently favorable outcomes. Methods The current study explored the combinatorial action of arsenic trioxide (ATO) and apatinib (APA) in vitro and in vivo. In vitro models were tested using -H446 and -H196 SCLC cell lines. The ability of drugs to reduce -metastasis, -cell proliferation, and -migration were assessed. Using bioinformatic analysis, differentially expressed genes were determined. Gene regulation was assessed using gene knock down models and confirmed using Western blots. The in vivo models were used to confirm the resolution of pathognomic features in the presence of the drugs. Growth factor receptor bound protein (GRB) 10 expression levels of human small cell lung cancer tissues and adjacent tissues were detected by IHC. Results In combination, ATO and APA were found to significantly reduce -cell proliferation, -migration, and -metastasis in both the cell lines. Cell proliferation was found to be inhibited by activation of Caspase-3, -7 pathway. In the presence of drugs, it was found that expression of GRB10 was stabilized. The silencing of GRB10 was found to negatively regulate the VEGFR2/Akt/mTOR and Akt/GSK-3β/c-Myc signaling pathway. Concurrently, absence of metastasis and reduction of tumor volume were confirmed in vivo. The immunohistochemical results confirmed that the expression level of GRB10 in adjacent tissues was significantly higher than that in human small cell lung cancer tissues. Conclusions Synergistically, ATO and APA have a more significant impact on inhibiting cell proliferation than each drug independently. ATO and APA may be mediating its action through the stabilization of GRB10 thus acting as a tumor suppressor. We thus, preliminarily report the impact of GRB10 stability as a target for SCLC treatment.

Abstract Spatial omics technologies decipher functional components of complex organs at cellular and subcellular resolutions. We introduce Spatial Graph Fourier Transform (SpaGFT) and apply graph signal processing to a wide range of spatial omics profiling platforms to generate their interpretable representations. This representation supports spatially variable gene identification and improves gene expression imputation, outperforming existing tools in analyzing human and mouse spatial transcriptomics data. SpaGFT can identify immunological regions for B cell maturation in human lymph nodes Visium data and characterize variations in secondary follicles using in-house human tonsil CODEX data. Furthermore, it can be integrated seamlessly into other machine learning frameworks, enhancing accuracy in spatial domain identification, cell type annotation, and subcellular feature inference by up to 40%. Notably, SpaGFT detects rare subcellular organelles, such as Cajal bodies and Set1/COMPASS complexes, in high-resolution spatial proteomics data. This approach provides an explainable graph representation method for exploring tissue biology and function.

Objective To assess short- and long-term changes in the upper airway, natural head position and hyoid bone position in skeletal Class Ⅲ patients after bimaxillary surgery. Methods In this retrospective study, the cone-beam computed tomography(CBCT) of skeletal Class Ⅲ patients was taken before surgery(T0), 3 months after surgery(T1) and 2 years after surgery(T2). Three-dimensional images were created to assess postoperative changes and the correlation between the upper airway, natural head position and hyoid bone was analyzed. Results Thirty skeletal Class Ⅲ patients(13 men and 17 women) who underwent bimaxillary surgery with a mean(SD)age of 21 years(a range of 17-30 years)were evaluated. A significant decrease was observed in the volume of palatopharynx, glossopharynx and total airway after T1 and T2. There was a significant correlation between changes in the position of the mandible and changes in the volume of the upper airway(P

The aim of this paper is to establish some fixed point results for enriched Kannan-type mappings in convex metric spaces. We first give an affirmative answer to a recent Berinde and Păcurar's question (Remark 2.3) [J. Comput. Appl. Math., 386 (2021), 113217]. Furthermore, we establish the existence and uniqueness of fixed points for Suzuki-enriched Kannan-type mappings in the setting of convex metric spaces. Finally, we present an application to approximate the solution of the Volterra integral equations to support our results.

Abstract Objective Bladder cancer(BCa) was a disease that seriously affects patients’ quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer. Methods We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms. Results The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group. Conclusion P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.

Abstract The nonconventional yeast Kluyveromyces marxianus has potential for industrial production, but the lack of advanced synthetic biology tools for precise engineering hinders its rapid development. Here, we introduce a CRISPR-Cas9-mediated multilocus integration method for assembling multiple exogenous genes. Using SlugCas9-HF, a high-fidelity Cas9 nuclease, we enhance gene editing precision. Specific genomic loci predisposed to efficient integration and expression of heterologous genes are identified and combined with a set of paired CRISPR-Cas9 expression plasmids and donor plasmids to establish a CRISPR-based biosynthesis toolkit. This toolkit enables genome integration of large gene modules over 12 kb and achieves simultaneous quadruple-locus integration in a single step with 20% efficiency. As a proof-of-concept, we apply the toolkit to screen for gene combinations that promote heme production, revealing the importance of HEM4Km and HEM12Sc. This CRISPR-based toolkit simplifies the reconstruction of complex pathways in K. marxianus, broadening its application in synthetic biology.

Abstract Background The 2018/2023 ESC/ESH Guidelines underlined a gap how baseline cardiovascular disease (CVD) risk predicted blood pressure (BP) lowering benefits. Further, 2017 ACC/AHA Guideline and 2021 WHO Guideline recommended implementation studies about intensive BP control. Now, to bridge these guideline gaps, we conducted a post hoc analysis to validate whether the baseline CVD risk influences the effectiveness of the intensive BP control strategy, which was designed by China Rural Hypertension Control Project (CRHCP). Methods This is a post hoc analysis of CRHCP, among which participants were enrolled except those having CVD history, over 80 years old, or missing data. Subjects were stratified into quartiles by baseline estimated CVD risk and then grouped into intervention and usual care group according to original assignment in CRHCP. Participants in the intervention group received an integrated, multi-faceted treatment strategy, executed by trained non-physician community health-care providers, aiming to achieve a BP target of

Background: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. Methods: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. Results: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P

Abstract In recombinant protein-producing yeast strains, cells experience high production-related stresses similar to high temperatures. It is possible to increase recombinant protein production by enhancing thermotolerance, but few studies have focused on this topic. Here we aim to identify cellular regulators that can simultaneously activate thermotolerance and high yield of recombinant protein. Through screening at 46 °C, a heat-resistant Kluyveromyces marxianus (K. marxianus) strain FDHY23 is isolated. It also exhibits enhanced recombinant protein productivity at both 30 °C and high temperatures. The CYR1N1546K mutation is identified as responsible for FDHY23’s improved phenotype, characterized by weakened adenylate cyclase activity and reduced cAMP production. Introducing this mutation into the wild-type strain greatly enhances both thermotolerance and recombinant protein yields. RNA-seq analysis reveals that under high temperature and recombinant protein production conditions, CYR1 mutation-induced reduction in cAMP levels can stimulate cells to improve its energy supply system and optimize material synthesis, meanwhile enhance stress resistance, based on the altered cAMP signaling cascades. Our study provides CYR1 mutation as a novel target to overcome the bottleneck in achieving high production of recombinant proteins under high temperature conditions, and also offers a convenient approach for high-throughput screening of recombinant proteins with high yields.

Objective To explore the role of indole-3-propionic acid (IPA) in the pathogenesis of metabolic associated fatty liver disease (MAFLD) induced by high-fat diet (HFD) in order to reveal the role and related mechanism of adipose tissue metabolism in the process. Methods A mouse model of MAFLD was induced by HFD. Male C57BL/6J mice (6~7 weeks old) were randomly divided into control group (CON), HFD group, and HFD+IPA intervention group (HFD+IPA). The CON group was fed with control diet, and the HFD group and HFD+IPA group were fed with 60% of high-fat diet. The experiment period was 12 weeks, and IPA was administered at 20 mg/(kg·d) for 6 weeks starting from the 7th week. The body weight and food intake of each group were monitored weekly. After the intervention, the body composition of mice was detected by animal body composition analyzer. After the mice were euthanized, the morphological and structural changes in the liver and adipose tissues were observed by HE staining, the indicators relevant to lipid metabolism in the serum, liver and adipose tissues were detected by automatic blood biochemical analyzer and biochemical kits, and the mRNA expression changes of lipid metabolism and inflammation related genes were detected by qRT-PCR. Results Compared with the CON group, the HFD group had significantly increased body weight and body fat percentage, obvious lipid deposition in the liver, obviously elevated serum alanine aminotransferase, aspartate aminotransferase, liver triglyceride and total cholesterol levels (P < 0.05), and raised mRNA levels of liver fatty acid transporter CD36 (P < 0.05), while IPA intervention significantly reversed the above changes (P < 0.05). IPA intervention significantly inhibited the HFD-induced enlargement of visceral and brown fat cells, reduced the content of visceral adipose tissue (VAT) and serum level of free fatty acids (P < 0.05), and increased the mRNA expression levels of VAT lipolysis (HSL, CGI58), browning genes (Cidea, ND5, UCP1, Prdm16) (P < 0.05), as well as those of brown adipose tissue (BAT) lipolysis (HSL, ATGL) and fatty acid beta oxidation (Cpt1a, PPARα) genes (P < 0.05). Meanwhile, the mRNA levels of TNF-α, IL-1β, CXCL1 and CCL2 in VAT and BAT were decreased after IPA intervention (P < 0.05). Conclusion IPA can improve the occurrence of MAFLD induced by HFD, and its mechanism may be closely associated with its regulation of BAT and VAT morphology, and the mRNA expression of metabolic function and inflammation related genes.

Abstract Background The standard curative treatments for extremity soft tissue sarcoma (ESTS) include surgical resection with negative margins and perioperative radiotherapy. However, the optimal resection margin remains controversial. This study aimed to evaluate the outcomes in ESTS between microscopically positive margin (R1) and microscopically negative margin (R0) according to the Union for International Cancer Control (UICC) (R + 1 mm) classification. Methods Medical records of patients with localized ESTS who underwent primary limb-sparing surgery and postoperative radiotherapy between 2004 and 2015 were retrospectively reviewed. Patients were followed for at least 5 years or till local or distant recurrence was diagnosed during follow-up. Outcomes were local and distal recurrences and survival. Results A total of 52 patients were included in this study, in which 17 underwent R0 resection and 35 underwent R1 resection. No significant differences were observed in rates of local recurrence (11.4% vs. 35.3%, p = 0.062) or distant recurrence (40.0% vs. 41.18%, p = 0.935) between R0 and R1 groups. Multivariate analysis showed that distant recurrences was associated with a Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade (Grade III vs. I, adjusted hazard ratio (aHR): 12.53, 95% confidence interval (CI): 2.67–58.88, p = 0.001) and tumor location (lower vs. upper extremity, aHR: 0.23, 95% CI: 0.07–0.7, p = 0.01). Kaplan–Meier plots showed no significant differences in local (p = 0.444) or distant recurrent-free survival (p = 0.161) between R0 and R1 groups. Conclusions R1 margins, when complemented by radiotherapy, did not significantly alter outcomes of ESTS as R0 margins. Further studies with more histopathological types and larger cohorts are necessary to highlight the path forward.

The forming technology of surface micropattern structure was widely used in practical manufacturing as a means to texture the surface of materials and to promote advanced and functional materials. The main methods of surface micropattern forming include hot embossing, chemical etching, electrical discharge machining(EDM), photolithography and 3D printing depending on the application areas of materials. The different surface micropattern structure forming techniques and the basic principles of preparing surface texturise functional materials were reviewed, and their practical applications in photovoltaics, electronic information, intelligent manufacturing, ultra-precision manufacturing and other fields were listed. The characteristics and scope of application of different surface micropattern structure forming technologies are summarized, and the key problems faced in realizing the surface texturisation and functionalization of materials are put forward, which provides certain reference for the micromachining technology of surface micropattern structures.

Study designRetrospective cohort study.ObjectiveTo compare the outcomes of patients with adult spinal deformity (ASD) following spinal fusion with the lowest instrumented vertebra (LIV) at L4/L5 versus S1/ilium.MethodsA multicenter ASD database was evaluated. Patients were categorized into 2 groups based on LIV levels-groups L (fusion to L4/L5) and S (fusion to S1/ilium). Both groups were propensity matched by age and preoperative radiographic alignments. Patient demographics, operative details, radiographic parameters, revision rates, and health-related quality of life (HRQOL) scores were compared.ResultsOverall, 349 patients had complete data, with a mean follow-up of 46 months. Patients in group S (n = 311) were older and had larger sagittal and coronal plane deformities than those in group L (n = 38). After matching, 28 patients were allocated to each group with similar demographic, radiographic, and clinical parameters. Sagittal alignment restoration at postoperative week 6 was significantly better in group S than in group L, but it was similar in both groups at the 2-year follow-up. Fusion to S1/ilium involved a longer operating time, higher PJK rates, and greater PJK angles than that to L4/L5. There were no significant differences in the complication and revision rates between the groups. Both groups showed significant improvements in HRQOL scores.ConclusionsFusion to S1/ilium had better sagittal alignment restoration at postoperative week 6 and involved higher PJK rates and greater PJK angles than that to L4/L5. The clinical outcomes and rates of revision surgery and complications were similar between the groups.

Study designComparative cohort study.ObjectiveFactors that influence the lower instrumented vertebra (LIV) selection in adult cervical deformity (ACD) are less reported, and outcomes in the cervicothoracic junction (CTJ) and proximal thoracic (PT) spine are unclear.MethodsA prospective ACD database was analyzed using the following inclusion criteria: LIV between C7 and T5, upper instrumented vertebra at C2, and at least a 1-year follow-up. Patients were divided into CTJ (LIV C7-T2) and PT groups (LIV T3-T5) based on LIV levels. Demographics, operative details, radiographic parameters, and the health-related quality of life (HRQOL) scores were compared.ResultsForty-six patients were included (mean age, 62 years), with 22 and 24 patients in the CTJ and PT groups, respectively. Demographics and surgical parameters were comparable between the groups. The PT group had a significantly higher preoperative C2-C7 sagittal vertical axis (cSVA) (46.9 mm vs 32.6 mm, P = 0.002) and T1 slope minus cervical lordosis (45.9° vs 36.0°, P = 0.042) than the CTJ group and was more likely treated with pedicle-subtraction osteotomy (33.3% vs 0%, P = 0.004). The PT group had a larger correction of cSVA (-7.7 vs 0.7 mm, P = 0.037) and reciprocal change of increased T4-T12 kyphosis (8.6° vs 0.0°, P = 0.001). Complications and reoperations were comparable. The HRQOL scores were not different preoperatively and at 1-year follow-up.ConclusionsThe selection of PT LIV in cervical deformities was more common in patients with larger baseline deformities, who were more likely to undergo pedicle-subtraction osteotomy. Despite this, the complications and HRQOL outcomes were comparable at 1-year follow-up.

We proposed a non-contact photoacoustic (PA) detection method using spectral domain optical coherence tomography (SDOCT). Two interference spectrums (A-lines) were acquired before and after the PA excitation with SDOCT. PA signal propagated within the sample causing the vibration. The vibration inner the sample introduced phase change between the acquired two A-lines. Thus, the PA signal can be detected by evaluating the difference in phase between the two A-lines. Based on the method, an OCT-PAM dual-mode imaging system was constructed. In the system, SDOCT served as the detection unit for PAM. Thus, the combination of the two imaging modalities was simplified. Another advantage of the system is that it realizes non-contact all-optic detection, which is attractive for biomedical imaging. Using the system, we imaged phantoms of carbon fibers, asparagus leaves and human hairs. Furthermore, the cortical vasculature of rat was imaged in vivo and the flow status was evaluated quantitatively.

In the study of cavitation in room-temperature fluids, the heat transfer between gas and liquid in bubble oscillation is usually assumed to be an adiabatic process for simplification. However, this heat transfer and thermodynamic mechanism is not yet understood in cryogenic fluids, especially under small amplitude oscillation conditions excited by ultrasonic field. This article studies bubble thermodynamic model under an external ultrasonic field based on the heat transfer equation for cryogenic fluids. The temperature changes inside bubbles are calculated, and the heat transfer mechanism is briefly analyzed. The results indicate that the heat transfer mechanism of bubbles depends on the relationship between ultrasonic frequency and bubble resonance frequency. By analyzing two special cases of dual-bubble and high-pressure environment, it is believed that heat transfer can be approximated as an adiabatic process under high-pressure conditions with ultrasonic frequency far from the resonance frequency. This conclusion can provide a theoretical basis for subsequent accurate calculation of heat-transfer polytropic coefficient, or void faction measurement in cryogenic two-phase flow.

IntroductionThe Xinjiang Mongolians, located along the Silk Road, migrated westward from Northeast Asia in the 13th and 14th centuries. Despite its significance, genetic studies on Xinjiang Mongolians have been limited compared to other Mongolian populations.MethodsIn this study, we analyzed the non-recombining region of the Y-chromosome in 165 Xinjiang Mongolian males using 108 biallelic markers and 44 STRs.Results and discussionOur study identified prevalent haplogroups C2a1a3-F1918 (10%), C2a1a2-M48 (8%), N1a1a-M178 (5%), and R1a1a-M17 (10%) in the Xinjiang Mongolians. Additionally, our study suggested a genetic affinity between Xinjiang Mongolians and Inner Mongolia Mongolian populations, as well as other ethnic groups from northwest China, based on the PCA analysis. The Network analysis revealed distinct branching expansion patterns in haplogroups C2a1a3a-F3796, C2a1a2-M48, and N1a1a-M178, with estimated timeframes aligning with Genghis Khan's invasion of Xinjiang in the Yuan Dynasty. Notably, our analysis of the R1a1a-M17 Network highlighted the role of Xinjiang Mongolians in the expansion of Turkic-speaking populations in Xinjiang and surrounding regions. The integration of ancient DNA data suggested that the high frequency haplogroups C2a1a3a-F3796, C2a1a2-M48, and N1a1a-M178 could be traced back to their origin in Northeast Asia. Furthermore, the estimated TMRCA of haplogroup R1a1a-M17 implied cultural and genetic influences from Turkic populations during the Qagatay Khanate period. Overall, our study provided a genetic explanation for the ethnic origin of Xinjiang Mongolians, highlighting their migration from Northeast Asia and subsequent assimilation with the local populations in Xinjiang.