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Lipases are important enzymes for various biotechnological applications. By using functional expression screening, lipZ03, a novel lipase gene, was isolated from a soil-derived metagenomic library. The gene was supposed to encode a protein of 617 amino acids with a C-terminal targeting signal region and four potential N-linked glycosylation sites. The protein sequence shared a conserved GXSXG motif (X represents any amino acid residue) with other microbial lipases. Gene lipZ03 was expressed in Pichia pastoris and the molecular weight was estimated to be approximately 65 kDa by electrophoresis. The optimum reaction temperature and pH value for LipZ03 was 50°C and 9.0, respectively. The enzyme was highly stable in the temperature range of 40-60°C and under alkaline conditions (pH 8-10). Lipolytic activity was significantly enhanced by Ca2+ and Mg2+ ions, but dramatically inhibited by Cu2+, Ni2+ and Hg2+ ions and EDTA. The purified enzyme preferentially hydrolyzed relatively long-chain triacylglycerols and was a true lipase rather than an esterase. Using a multi-stepwise methanol supply, the purified LipZ03 achieved a conversion yield of biodiesel production up to 74% after 36 h. Some interesting characteristics described here showed that the recombinant lipase may have potential to be a useful enzyme in industrial applications. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The Production and Supply of Electric and Heat Power Industry is an important energy supply sector in China. In this article, we apply the Logarithmic Mean Divisia Index decomposition method to analyze the carbon emissions of China's electricity and thermal supply industry from 2003 to 2012. Under different scenarios, this study also forecasts the carbon emissions and calculates reduction potential of The Production and Supply of Electric and Heat Power Industry. The results show the economic output effect and energy intensity effect promote the sector's CO2 emissions growth, however the energy structure effect decrease the sector's carbon emissions. At the end of 2030, the accumulated emission reduction will be 4160.84 Mt in moderate reduction scenario and 11,593.27 Mt in strong reduction scenario. If all the indexes maintain the current change rate, the industry will reach carbon emissions peak at the time of 2030, What is more, the time for emissions peak will be 2025 and 2020 in moderate reduction scenario and strong reduction scenario. Finally, the article proposes to improve energy efficiency and promote the development of clean energy to reduce the carbon emissions of the Production and Supply of Electric and Heat Power Industry. Draw more stringent environmental standards and incentives to promote energy‐saving existing technology, the application can also combine with the means of financial subsidies to encourage the companies to reduce the energy intensity of the sector or strengthen the impact of energy intensity effect on the change of carbon emissions, promote the industry early peak. © 2019 American Institute of Chemical Engineers Environ Prog, 38:e13146, 2019 [ABSTRACT FROM AUTHOR]

The factors influencing the elastic modulus [K(t)] of thermoplastic elastomers (TPEs) were investigated under spherical indentation mode with the instantaneous volumetric strain method. The TPE samples were prepared by the hot‐pressing method, and the variation in K(t) was investigated at different thicknesses, loading forces, and spherical indenter radii (Rs). The results demonstrate that the K(t) values of the TPEs decreased nonlinearly with the depth–radius ratio. The sample thickness [H(t)] and R showed positive and negative relationships with K(t), respectively. However, the loading force did not exhibit any significant effect on K(t). In a certain depth–radius ratio range, K(t) had strong functional relationships with H(t), R, and indentation depth. These results provide a reference for the mechanical property investigation of elastoplastic materials. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47181. [ABSTRACT FROM AUTHOR]

Objective: Aneurysm rupture is often a fatal complication of giant intradural aneurysm (GIA) treatments. The purpose of this study was to review aneurysm rupture in GIA treatment.Materials and Methods: We performed a systematic review on aneurysm rupture related to GIA treatment. For each reported case, we collected the following information: aneurysm location, size and rupture status, the mode of treatment, timing of the hemorrhage, anatomical, and hemodynamic factors.Results: We identified 56 aneurysm ruptures related to treatment in 38 published studies. Of the nine intraoperative ruptures, eight occurred during endovascular procedures and one in surgical treatment. Of the 47 delayed ruptures, 72.3% occurred within 2 weeks. The prognosis of intraoperative and delayed ruptures was poor, with 83.9% experiencing death. Of these aneurysms, 75% were initially unruptured. Of the delayed ruptured aneurysms, 21.3% had prior surgical treatment, 74.4% had prior endovascular treatment, and 4.3% had prior combined surgical and endovascular treatments. Vertebrobasilar artery (VBA) location was significantly associated with aneurysm rupture after treatment, occurring at 57.2%. Flow diverter (FD) treatment seemed to elevate the delayed rupture proportion of giant paraclinoid internal carotid artery (ICA) aneurysms from 22.0% to 42.9%. FD treatment did not lower the rupture risk of giant VBA aneurysms and the corresponding death rate.Conclusion: Intraoperative and delayed aneurysm ruptures were the most challenging in endovascular treatment of GIAs. Giant VBA aneurysm had the highest rupture risk after treatment. FD seemed to elevate the delayed rupture proportion of giant paraclinoid aneurysms. [ABSTRACT FROM AUTHOR]

Background: Hepatic epithelioid hemangioendothelioma (HEH) is extremely rare, and CT features have never been analyzed in a large group of patients. Methods: A retrospective study was designed to review the contrast-enhanced CT images of HEH patients. Intrahepatic lesions were categorized into three types: nodular, locally coalescent (coalescent lesion contained in one segment) or diffusely coalescent (coalescent lesion occupied more than one segment). CT features were compared among lesions of different sizes and patients with different lesion types. Results: A total of 93 HEH patients were included in this study, and 740 lesions were analyzed. The results of per-lesion analysis showed that medium lesions (2–5 cm) had the highest rate of lollipop sign (16.8%) and target-like enhancement (43.1%), while lesions in large group (> 5 cm) had the highest rate of capsular retraction (38.8%) and vascular invasion (38.8%). The differences on enhancement pattern and the rates of lollipop sign and capsular retraction were significant among lesions of different sizes (p < 0.001, respectively). The results of per-patient analysis showed that patients in locally coalescent group had the highest rates of lollipop sign (74.3%) and target sign (94.3%). All patients in diffusely coalescent group had capsular retraction and vascular invasion. CT appearances of capsular retraction, lollipop sign, target sign and vascular invasion differed significantly among patients with different lesion types (p < 0.001, p = 0.005, p = 0.006 and p < 0.001, respectively). Conclusion: CT features variated among HEH patients with different lesion types, and radiological appearances of HEH should be classified into nodular type, locally coalescent type and diffusely coalescent type. Key points: CT appearances of HEH differed significantly among lesions of different sizes. HEH lesions were categorized into three types: nodular, locally and diffusely coalescent. CT characteristics of HEH variated greatly among the three lesion types. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the efficiency of our chemically synthesized TT-00420, a novel spectrum-selective multiple protein kinase inhibitor, in cultured cells and animal models of gallbladder cancer (GBC) and explore its potential mechanism. Methods: Multiple GBC models were established to assess the anti-tumor efficiency, toxicity, and pharmacokinetics of TT-00420. Integrated transcriptomic, proteomic and phosphoproteomic analysis was conducted to identify potential downstream effectors of TT-00420. Western blotting, qRT-PCR, nuclear-cytoplasm separation, and immunofluorescence were performed to confirm the multi-omic results and explore the molecular mechanism of TT-00420. Immunohistochemistry was used to detect FGFR1 and p-FGFR1 expression levels in GBC samples. Autodock software was utilized to investigate the potential binding mode between the TT-00420 and the human FGFR1. Results: We found that TT-00420 exerted potent growth inhibition of GBC cell lines and multiple xenograft models. Treatment of mice with 15 mg/kg TT-00420 via gavage displayed a half-life of 1.8 h in the blood and rapid distribution to the liver, kidneys, lungs, spleen, and tumors at 0.25 h, but no toxicity to these organs over 2 weeks. Multi-omic analysis revealed c-Jun as a potential downstream effector after TT-00420 treatment. Mechanistically, TT-00420 showed rigorous ability to block FGFR1 and its downstream JNK-JUN (S63/S73) signaling pathway, and induce c-Jun S243-dependent MEK/ERK reactivation, leading to FASLG-dependent tumor cell death. Finally, we found that FGFR1 and p-FGFR1 expression was elevated in GBC patients and these levels correlated with decreased patient survival. Conclusions: TT-00420 shows potent antitumor efficacy and may serve as a novel agent to improve GBC prognosis. [ABSTRACT FROM AUTHOR]

In order to solve the problem of maximizing the utilization of resources through reasonable deployment under limited resources, this paper studies from two aspects: one is to establish the mathematical model of maximum coverage of space detection, and the other is to improve the harmony algorithm. The exploration performance and convergence performance of the harmony search algorithm are analyzed theoretically, and the more general formulas of exploration performance and convergence performance are proved. Based on theoretical analysis, the algorithm called opposition-based learning parameter adjusting harmony search is proposed. By using the algorithm to test the functions of different properties, the value range of key control parameters of the algorithm are given. The proposed algorithm is applied to optimize the problem of radar deployment. This paper takes a certain area of the Shandong Peninsula as the deployment scope. The simulation results show that the proposed algorithm is effective and practical. Although there is a large amount of calculation, it provides ideas and ways for other problems, such as the site selection of new observation and communication post, the deployment of maneuvering radar stations, and the track planning of fleet. [ABSTRACT FROM AUTHOR]

[Display omitted] Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various tumors. The activation of tyrosine kinases such as ERBB2 is the mechanism by which cholecystitis transforms into gallbladder cancer (GBC), therefore, it is important to investigate the relationship between long-term exposure to soy isoflavones and the occurrence and progression of GBC. This case-control study (n = 85 pairs) found that the high level of plasma soy isoflavone—genistein (GEN) was associated with a lower risk of gallbladder cancer (≥326.00 ng/mL compared to ≤19.30 ng/mL, crude odds ratio 0.15, 95% CI 0.04–0.59; P for trend = 0.016), and that the level of GEN exposure negatively correlated with Ki67 expression in GBC tissue (n = 85). Consistent with these results, the proliferation of GBC cells was inhibited in the long-term exposure models of GEN in vitro and in vivo. The long-term exposure to GEN reduced the tyrosine kinase activity of ERBB2 and impaired the function of the PTK6-AKT-GSK3β axis, leading to downregulation of the MCM complex in GBC cells. In summary, long-term exposure to GEN associated with soy products intake might play a certain role in preventing GBC and even inhibiting the proliferation of GBC cells. [ABSTRACT FROM AUTHOR]

Gallbladder cancer (GBC) is among the most common malignancies of biliary tract system due to its limited treatments. The immunotherapeutic targets for T cells are appealing, however, heterogeneity of T cells hinds its further development. We systematically construct T cell atlas by single-cell RNA sequencing; and utilized the identified gene signatures of high_CNV_T cells to predict molecular subtyping towards personalized therapeutic treatments for GBC. We identified 12 T cell subtypes, where exhausted CD8+ T cells, activated/exhausted CD8+ T cells, and regulatory T cells were predominant in tumors. There appeared to be an inverse relationship between Th17 and Treg populations with Th17 levels significantly reduced, whereas Tregs were concomitantly increased. Furthermore, we first established subtyping criterion to identify three subtypes of GBC based on their pro-tumorigenic microenvironments, e.g., the type 1 group shows more M2 macrophages infiltration, while the type 2 group is infiltrated by highly exhausted CD8+ T cells, B cells and Tregs with suppressive activities. Our study provides valuable insights into T cell heterogeneity and suggests that molecular subtyping based on T cells might provide a potential immunotherapeutic strategy to improve GBC treatment. • Providing a valuable resource in unveiling the diverse T cell heterogeneity in GBCs. • Three molecular subtypes were established from the characteristics of T cells. • The type 1 group shows substantial infiltration of M2 macrophages. • The type 2 group displays infiltration by highly exhausted CD8+ T, B and Treg cells. [ABSTRACT FROM AUTHOR]

A vehicle model with active suspension system is built, and the LQG control algorithm is adopted with both road roughness and the roll moment of car body as disturbance signals of vehicle system, the optimal control force for vehicle steering operation is calculated. Then a co-simulation on the coordinated control of the ride comfort and handling stability of vehicle running on A-class road and C-class road is conducted with step and single-cycle sine wave inputs of steering wheel respectively. The results show that compared with passive suspension, the coordinated control strategy proposed for active suspension can enhance the handling stability of vehicle without impeding the improvement of ride comfort. [ABSTRACT FROM AUTHOR]

Background: Gallbladder cancer (GBC) is the most common cancer type of the biliary tract, and an association has been found between chronic calculous cholecystitis (CCC) and an increased incidence of GBC mortality. An understanding of the relationship between CCC and its carcinogenesis may enable us to prevent and cure GBC. In this study, we attempted to explore changes in the microbiome profile that take place during the transition from chronic cholecystitis mucosa to malignant lesions. Results: Seven paired human GBC and CCC samples were provided by patients who had undergone laparoscopic cholecystectomy or radical cholecystectomy. Mucosal DNA extraction and metagenomic sequencing were performed to evaluate changes in the microbiota between the two groups. We found that GBC patients and CCC patients shared similar stable and permanent dominant species and showed apparent differences in their biliary microbial composition and gene function. Peptostreptococcus stomatis and Enterococcus faecium may potentially play a role in GBC progression. In addition, the metagenomic species profiles, co‐abundance and co‐exclusion correlations, and CAZyme prevalence showed significant differences between the CCC and GBC groups. Conclusion: Our data suggested that changes in the microbiota between CCC and GBC may help deepen our understanding of the complex spectrum of different microbiotas involved in the development of GBC. Although the cohort size was small, this study has presented the first evidence of the existence of an altered biliary microbiota in GBC, which is clearly different from that in CCC patients. [ABSTRACT FROM AUTHOR]

Polyacrylonitrile (PAN) was cyclized by heating in an inert atmosphere and then dissolved in sulfuric acid and oxidized by nitric acid, resulting in product named OCPAN. The OCPAN was dissolved along with PAN and spun into fibers, getting modified PAN fiber (MPAN), to realize self-crosslinking and direct carbonization. The chemical structure of the OCPAN and its compatibility and co-carbonization effects with PAN were characterized through characterization methods of optical microscopy, Fourier transform infrared spectroscopy and thermogravimetric analysis. The structure and properties of the resultant carbon fibers were investigated by scanning electron microscope and monofilament strength tester. The results show that ketone aromatic heterocycles are produced in OCPAN, which are able to promote the formation of a stable structure of carbon network and produce crosslinking with PAN molecules. The carbon yield of the MPAN fiber after direct carbonation under 900 °C temperature in nitrogen is 23% higher than that of the PAN fiber without oxidation carbonized under the same condition, while the strength of the final carbon fiber is a bit lower than that derived from the PAN fiber through pre-oxidation. Therefore, the direct carbonation of PAN fiber is basically realized. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to report the prevalence of liver haemangioma and describe growth rates by age. Methods A retrospective study of people undergoing a health examination. The collected data included gender, age, presence or absence and size of liver haemangioma. A second database of liver haemangioma patients with a minimum follow up period of 5 years was analysed. The collected data included gender, initial age at diagnosis, follow-up period, initial and final size. Results Patients were divided into four age groups: 20–29 years, 30–39 years, 40–49 years and ≥50 years. Patients in the 20–29 years group had the lowest prevalence of liver haemangioma (1.78%) and the smallest size (1.3 ± 0.7 cm), while 40–49 years group had the highest prevalence (3.94%) and largest size (1.9 ± 1.3 cm). Patients between 30 and 39 years had the greatest increase in haemangioma size (4.0 cm, (3.0, 6.0) cm), while patients of ≥50 years had the least (1.4 cm (0.5, 3.8) cm). The proportion of patients without an increase in haemangioma size increased with age (P = 0.031). Conclusion Age is an important factor affecting the prevalence and growth rate of liver haemangioma. [ABSTRACT FROM AUTHOR]

Despite of the high lethality of gallbladder cancer (GBC), little is known regarding molecular regulation of the tumor immunosuppressive microenvironment. Here, we determined tumor expression levels of YKL-40 and the molecular mechanisms by which YKL-40 regulates escape of anti-tumor immune surveillance. We found that elevated expression levels of YKL-40 in plasma and tissue were correlated with tumor size, stage IV and lymph node metastasis. Single cell transcriptome analysis revealed that YKL-40 was predominantly derived from M2-like subtype of infiltrating macrophages. Blockade of M2–like macrophage differentiation of THP-1 cells with YKL-40 shRNA resulted in reprogramming to M1-like macrophages and restricting tumor development. YKL-40 induced tumor cell expression and secretion of growth differentiation factor 15 (GDF15), thus coordinating to promote PD-L1 expression mediated by PI3K, AKT and/or Erk activation. Interestingly, extracellular GDF15 inhibited intracellular expression of GDF15 that suppressed PD-L1 expression. Thus, YKL-40 disrupted the balance of pro- and anti-PD-L1 regulation to enhance expression of PD-L1 and inhibition of T cell cytotoxicity, leading to tumor immune evasion. The data suggest that YKL-40 and GDF15 could serve as diagnostic biomarkers and immunotherapeutic targets for GBC. • Increased YKL-40 in plasma were correlated with tissue expression of YKL-40 and GBC progression. • Blockade of YKL-40 in M2-like macrophages resulted in M1-like macrophage reprogramming. • YKL-40 promoted GDF15 secretion, which in turn inhibited intracellular GDF15 function that suppressed PD-L1 expression. • YKL-40 and GDF15 induced PD-L1 expression and abrogated cytotoxicity of infiltrating CD8+ T lymphocytes. [ABSTRACT FROM AUTHOR]

Potassium permanganate, nitrate and acetate acid precursors of manganese were used to as precursors of manganese to prepare dispersed manganese oxides on MCM-41 catalysts (MnO x /MCM-41), in order to compare the structure and activity. MnO x /MCM-41 were synthesized by impregnation method and calcined at different temperatures. The catalytic properties of these materials were investigated for the oxidation of benzyl alcohol using hydrogen peroxide as oxygen source. Catalysts were characterized by X-ray diffraction, N 2 adsorption, H 2 temperature programmed reduction, X-ray photoelectron spectroscopy and UV–Vis diffuse reflectance spectra. It was observed that the varieties of manganese precursors and calcination temperature affect the oxidation state and reducibility of MnO x , which play significant role in the catalytic process. The catalysts prepared from the potassium permanganate and acetate precursors exhibited the outstanding catalytic activity, which could be related to the reducibility of the surface Mn δ+ oxo species. It was found that the Mn 4+ and Mn 3+ oxo species present a higher intrinsic activity than that of Mn 2+ oxo species. [ABSTRACT FROM AUTHOR]

Background: The anticoagulation strategy of switching to rivaroxaban after 1 week of initial low-molecular-weight heparin (LMWH) therapy is recommended by a guideline for the treatment of acute iliofemoral deep vein thrombosis (DVT). However, the initial rivaroxaban dose in the switching strategy, as well as the effectiveness and safety of the early switching (less than 1 week) to rivaroxaban, remain inadequately substantiated. We aimed to evaluate the effectiveness and safety of early switching from LMWH to maintenance therapy of rivaroxaban (20 mg once daily) for acute iliofemoral DVT., Methods: A retrospective cohort study was conducted using data from patients with acute iliofemoral DVT who received initial LMWH anticoagulation followed by rivaroxaban maintenance therapy. The clinical outcomes were compared between early (LMWH course ≤7 days) and routine (LMWH course >7 days) switching strategies within 3 months of initiating anticoagulation., Results: 217 patients were included, 59 (27.2%) receiving early switching and 158 (72.8%) receiving routine switching. Compared with routine switching, patients with early switching had a significantly shorter hospital stay (7 days vs. 14 days, P < 0.001). The length of hospital stay was significantly positively correlated with the duration of LMWH (r = 0.762, P < 0.001). The incidences of recurrent venous thromboembolism (5.1% vs. 2.5%, P = 0.606), major bleeding (0% vs. 1.9%, P = 0.564), clinically relevant nonmajor bleeding (1.7% vs. 2.5%, P = 1.000) and all-cause mortality (6.8% vs. 2.5%, P = 0.283) were not statistically different between the 2 groups., Conclusions: Direct early switching from LMWH to maintenance therapy of rivaroxaban is effective and safe for acute iliofemoral DVT., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Deep vein thrombosis (DVT) provoked by orthopedic trauma is increasing in pediatric hospitalized patients. The purpose of our study is to identify the prevalence of acute DVT in pediatric and adolescent orthopedic trauma hospitalized patients and focus on evaluating the anticoagulation strategies and the clinical outcomes after a confirmed acute DVT., Methods: Patients (age ≤18 years) with a confirmed acute DVT admitted for orthopedic trauma between September 2017 and December 2023 were included. Patients were classified into the non-anticoagulation (NA), the in-hospital anticoagulation (IHA), and the in-and-out-of-hospital anticoagulation (IOHA) groups based on their anticoagulation regimen. Efficacy outcomes were the venous thromboembolism (VTE) recurrence within 3 months and change in thrombus burden by repeat imaging at 2 weeks after discharge compared with baseline. Safety outcomes were major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) within 3 months., Results: Of the 11,206 pediatric and adolescent orthopedic trauma inpatients, 94(median age,16 [15, 18] years) were diagnosed with acute DVT, with an incidence of 0.84 %, of which 8(8.5 %) received NA, 41(43.6 %) received IHA, and 45(47.9 %) received IOHA. After the diagnosis of DVT, of patients who received anticoagulation, 97.9 % were treated with rivaroxaban as an oral anticoagulant, and 71.7 % received an LMWH course of ≥5 days before starting rivaroxaban therapy. With a median anticoagulation course of 22(8, 37.3) days, the duration in the IOHA was significantly longer than the IHA (37 days vs. 8 days, p = 0.000). No patients experienced recurrent VTE and MB at 3 months, and 1 received IOHA had a CRNMB event (0 % vs. 0 % vs. 2.2 %, p = 1.000). Thrombus resolution was significantly higher in patients who received anticoagulation therapy (IOHA 91.1 % vs. IHA 80.5 % vs. NA 37.5 %, P = 0.002), and thrombus-no relevant change was significantly lower in patients who received the IOHA strategy compared with the other groups (4.4 % vs. 19.5 % vs. 62.5 %, P = 0.000)., Conclusions: A rivaroxaban-predominant IOHA strategy significantly reduced the thrombotic burden without increasing the risk of bleeding for the treatment of DVT in adolescents with orthopedic trauma. Duration of anticoagulation therapy <6 weeks appears appropriate for adolescent orthopedic trauma-related DVT., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Growing evidence suggests that symptoms associated with post-COVID-19 condition (also known as long COVID) can affect multiple organs and systems in the human body, but their association with viral persistence is not clear. The aim of this study was to investigate the persistence of SARS-CoV-2 in diverse tissues at three timepoints following recovery from mild COVID-19, as well as its association with long COVID symptoms., Methods: This single-centre, cross-sectional cohort study was done at China-Japan Friendship Hospital in Beijing, China, following the omicron wave of COVID-19 in December, 2022. Individuals with mild COVID-19 confirmed by PCR or a lateral flow test scheduled to undergo gastroscopy, surgery, or chemotherapy, or scheduled for treatment in hospital for other reasons, at 1 month, 2 months, or 4 months after infection were enrolled in this study. Residual surgical samples, gastroscopy samples, and blood samples were collected approximately 1 month (18-33 days), 2 months (55-84 days), or 4 months (115-134 days) after infection. SARS-CoV-2 was detected by digital droplet PCR and further confirmed through RNA in-situ hybridisation, immunofluorescence, and immunohistochemistry. Telephone follow-up was done at 4 months post-infection to assess the association between the persistence of SARS-CoV-2 RNA and long COVID symptoms., Findings: Between Jan 3 and April 28, 2023, 317 tissue samples were collected from 225 patients, including 201 residual surgical specimens, 59 gastroscopy samples, and 57 blood component samples. Viral RNA was detected in 16 (30%) of 53 solid tissue samples collected at 1 month, 38 (27%) of 141 collected at 2 months, and seven (11%) of 66 collected at 4 months. Viral RNA was distributed across ten different types of solid tissues, including liver, kidney, stomach, intestine, brain, blood vessel, lung, breast, skin, and thyroid. Additionally, subgenomic RNA was detected in 26 (43%) of 61 solid tissue samples tested for subgenomic RNA that also tested positive for viral RNA. At 2 months after infection, viral RNA was detected in the plasma of three (33%), granulocytes of one (11%), and peripheral blood mononuclear cells of two (22%) of nine patients who were immunocompromised, but in none of these blood compartments in ten patients who were immunocompetent. Among 213 patients who completed the telephone questionnaire, 72 (34%) reported at least one long COVID symptom, with fatigue (21%, 44 of 213) being the most frequent symptom. Detection of viral RNA in recovered patients was significantly associated with the development of long COVID symptoms (odds ratio 5·17, 95% CI 2·64-10·13, p<0·0001). Patients with higher virus copy numbers had a higher likelihood of developing long COVID symptoms., Interpretation: Our findings suggest that residual SARS-CoV-2 can persist in patients who have recovered from mild COVID-19 and that there is a significant association between viral persistence and long COVID symptoms. Further research is needed to verify a mechanistic link and identify potential targets to improve long COVID symptoms., Funding: National Natural Science Foundation of China, National Key R&D Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and New Cornerstone Science Foundation., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: The progression of gallbladder cancer (GBC) is accompanied by abnormal fatty acid β-oxidation (FAO) metabolism. Different types of lipids perform various biological functions. This study aimed to determine the role of acyl carnitines in the molecular mechanisms of GBC progression., Methods: Distribution of lipids in GBC was described by LC-MS-based lipidomics. Cellular localization, expression level and full-length of lncBCL2L11 were detected using fluorescence in situ hybridization (FISH) assays, subcellular fractionation assay and 5' and 3' rapid amplification of the cDNA ends (RACE), respectively. In vitro and in vivo experiments were used to verify the biological function of lncBCL2L11 in GBC cells. Methylated RNA Immunoprecipitation (MeRIP) was performed to detect the methylation levels of lncBCL2L11. RNA pull-down assay and RNA immunoprecipitation (RIP) assay were used to identify lncBCL2L11 interacting proteins. Co-Immunoprecipitation (Co-IP) and Western blot assay were performed to validate the regulatory mechanism of lncBCL2L11 and THO complex., Results: Acylcarnitines were significantly up-regulated in GBC tissues. High serum triglycerides correlated to decreased survival in GBC patients and promoted tumor migration. LncBCL2L11 was identified in the joint analysis of highly metastatic cells and RNA sequencing data. LncBCl2L11 prevented the binding of THOC6 and THOC5 and causes the degradation of THOC5, thus promoting the accumulation of acylcarnitines in GBC cells, leading to the malignant progression of cancer cells. In addition, highly expressed acylcarnitines stabilized the expression of lncBCL2L11 through N 6 -methyladenosine methylation (m6A), forming a positive feedback regulation in tumor dissemination., Conclusions: LncBCL2L11 is involved in gallbladder cancer metastasis through FAO metabolism. High lipid intake is associated with poor prognosis of GBC. Therefore, targeting lncBCL2L11 and its pathway-related proteins or reducing lipid intake may be significant for the treatment of GBC patients., (© 2024. The Author(s).)

Objective: To explore the risk factors for inferior vena cava filter (IVCF) thrombus in orthopedic trauma patients who underwent filter placement with ongoing anticoagulation in clinical settings., Methods: We retrospectively analyzed clinical data from fracture patients with lower extremity acute deep vein thrombosis (DVT) implanted with an IVCF admitted to Tianjin Hospital from January 2017 to December 2019. Potential risk factors, such as gender, age, diabetes, hypertension, fracture sites, thrombus location, free-floating thrombus, filter type, Injury Severity Score (ISS), and postoperative D-dimer values, were analyzed by the Chi-square test, t-test, logistic regression, and receiver operating characteristic (ROC) curve analysis., Results: A total of 662 patients were included in our study, and filter-related thrombosis was present in 67 (10.1%) patients. No significant differences were observed in age, gender, hypertension, diabetes, fracture site, free-floating thrombus, filter type, indwelling time, and postoperative D-dimer level. Thrombus location and ISS were significantly different ( p < 0.05). Popliteal DVT (P-DVT) (odds ratio [OR]: 2.130, p = 0.018) and ISS (OR: 1.135, p = 0.000) were associated with filter thrombus. Patients with P-DVT were prone to a small filter thrombus (OR: 3.231, p = 0.037). From the ROC curve analysis, the diagnostic value of ISS was 24.5 and 26.5 for patients with filter and massive filter thrombus, respectively., Conclusion: Thrombus location and ISS were independent risk factors for filter thrombus in patients with traumatic fractures. P-DVT had a higher potential to result in a small filter thrombus and an ISS value >26.5, which was considered a significant massive filter thrombus predictor., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Hepatic epithelioid hemangioendothelioma (EHE) is an extremely rare tumor, and no standard therapy has been established yet., Objectives: The aim of this study was to investigate the short-term results of combined therapy with sirolimus and interferon-alpha 2b (IFN-a 2b) (SI therapy)., Methods: From January 2022 to April 2023, 40 patients histologically diagnosed with hepatic EHE and progressive disease received SI therapy. All patients were regularly evaluated for the safety and efficacy of the SI therapy. Patients who received SI therapy for <3 months without a tumor status evaluation after treatment were excluded., Results: Twenty-nine patients with hepatic EHE were included in this study. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 19 (65.5%) patients and 1 in 10 (34.5%) patients. The median duration of the SI therapy was 8 months (range, 3-15 months). Twenty-three (79.3%) patients showed a decrease in tumor size, including 11 (37.9%) patients who achieved a partial response and one (3.4%) who achieved a complete response; the objective response rate was 41.4%. Stable disease was observed in 13 (44.8%) patients, with a disease control rate of 86.2%. Adverse events (AES) were observed in 18 patients, including leukopenia (31.0%), oral ulcers (13.8%), and liver injury (10.3%). No severe (grade ⩾ 3) AEs were recorded, and SI therapy was not interrupted for any patient due to AEs., Conclusion: Sirolimus and IFN-a 2b may have synergistic effects in the treatment of hepatic EHE. SI therapy is a safe and effective treatment for hepatic EHE patients with good ECOG performance status., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Malignant tumors represent a formidable global health challenge, compelling the pursuit of innovative treatment modalities. Oncolytic therapy has emerged as a promising frontier in antitumor strategies. However, both natural agents (such as oncolytic bacteria or viruses) and synthetic oncolytic peptides confront formidable obstacles in clinical trials, which include the delicate equilibrium between safety and efficacy, the imperative for systemic administration with targeted therapy, and the need to counteract oncolysis-induced immunosuppression. To overcome these dilemmas, we have developed biomimetic nanoengineering to create oncolytic bacteria-inspired nanosystems (OBNs), spanning from hierarchical structural biomimicry to advanced bioactive biomimicry. Our OBNs harbor inherent oncolytic potential, including functionalized oligosaccharides mimicking bacterial cell walls for optimal blood circulation and tumor targeting, tumor acidity-switchable decoration for tumor-specific oncolysis, stereospecific tryptophan-rich peptides for robust oncolytic activity, encapsulated tumor immunomodulators for enhanced immunotherapy, and innate multimodal imaging potential for biological tracing. This work elucidates the efficacy and mechanisms of OBNs, encompassing primary tumor suppression, metastasis prevention, and recurrence inhibition. Systemic administration of d-chiral OBNs has demonstrated superior oncolytic efficacy, surpassing intratumoral injections of clinical-grade oncolytic peptides. This work heralds an era in biomimetic engineering on oncolytic agents, promising the revolutionization of contemporary oncolytic therapy paradigms for clinical translation.

The mixing quality of polymer melts in the mixing section of a single-screw extruder and an injection molding machine has considerable effects on the properties of the molded products. Therefore, the study of the flow field of polymer melts in the mixing section is of great importance. The lattice Boltzmann method (LBM) exhibits unique advantages in simulating non-Newtonian fluids. Many researchers have used LBM to study the flow of medium- and low-viscosity fluids. In their studies, the Reynolds number of fluid flows is generally moderate. However, polymer melts are typical high-viscosity fluids, and their flow Reynolds number is generally very small. The single-relaxation-time lattice Boltzmann method (SRT-LBM) has been used previously to study the flow field of power law fluids in the mixing section. Herein, the flow field of high-viscosity generalized Newtonian fluids in the mixing section of a single-screw extruder is studied using SRT-LBM, the two-relaxation-time lattice Boltzmann method (TRT-LBM), and the multiple-relaxation-time lattice Boltzmann method (MRT-LBM). Through comparison, TRT-LBM has been found to exhibit obvious advantages regarding stability, calculation accuracy, calculation efficiency, and selection of simulation parameters. The TRT-LBM is more suitable for studying high-viscosity generalized Newtonian fluids than SRT-LBM and MRT-LBM. SRT-LBM has low computational efficiency when simulating high-viscosity generalized Newtonian fluids, and instability is easily caused when the fluid has a yield stress. For MRT-LBM, only by studying the relaxation parameters can its advantages be fully utilized. However, optimizing the accuracy and stability of the MRT-LBM via parameter research and linear stability analysis is difficult. For non-Newtonian fluids, it is difficult to optimize the relaxation parameters to make the MRT-LBM more stable and accurate than the TRT-LBM. It is difficult for the MRT-LBM to realize its potential when simulating high-viscosity generalized Newtonian fluids. In addition, we studied the flow pattern in the cross section of the screw channel and compared it to the results reported in previous studies., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background and Aims: Nicotinamide N -methyltransferase (NNMT), an enzyme responsible for the methylation of nicotinamide, is involved in many metabolic pathways in adipose tissue and the liver. However, the role of NNMT in editing the tumor immune microenvironment is not well understood., Approach and Results: Here, we identified that NNMT can promote IL6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression by decreasing the tri-methyl-histone H3 levels on the promoters of IL6 and CSF2 (encoding GM-CSF) and CCAAT/Enhancer Binding Protein, an essential transcription factor for IL6 expression, thus promoting differentiation of macrophages into M2 type tumor-associated macrophages and generation of myeloid-derived suppressor cells from peripheral blood mononuclear cells. Treatment of xenografted tumor models overexpressing NNMT gallbladder carcinoma (GBC) cells with the NNMT inhibitor JBSNF-000088 resulted in compromised tumor development and decreased expression levels of IL6, GM-CSF, tumor-associated macrophage marker CD206, and myeloid-derived suppressor cell marker CD33 but increased expression levels of CD8. In addition, elevated expression of NNMT in tumors of patients with GBC was correlated with increased expression levels of CD206 and CD33 but with decreased levels of CD8 and survival of patients., Conclusions: These data highlight the critical role of NNMT in GBC progression. Inhibition of NNMT by JBSNF-000088 is a potential molecular target for GBC immunotherapy., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated., Methods: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry., Results: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 ., Conclusion: ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC., (Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Synthesizing biomimetic systems with stereospecific architectures and advanced bioactivity remains an enormous challenge in modern science. To fundamentally eliminate biosafety issues of natural oncolytic viruses, the development of synthetic virus-inspired particles with high oncolytic activity is urgently needed for clinical antitumor treatments. Here, we describe the design and synthesis of enantiomeric virus-inspired particles for efficient oncolytic therapy from homochiral building blocks to stereospecific supramolecular constructions. The L-virus-inspired oncolytic particles (L-VOPs) and D-VOPs possess similar biomimetic nanostructures but mirror-imaged enantiomeric forms. It is important that both L-VOPs and D-VOPs successfully mimic the pharmacological activity of oncolytic viruses, including direct tumor lysis and antitumor immune activation. D-VOPs provide quite better oncolytic efficacy than that of clinical-grade oncolytic agents (LTX-315, IC 50 = 53.00 μg mL -1 ) with more than 5-fold decrease in IC 50 value (10.93 μg mL -1 ) and close to 100% tumor suppression (98.79%) against 4T1 tumor-bearing mice, attributed to the chirality-dependent tumor recognition, interaction, antidegradation, and immunotherapy. This work provides a strategy for the synthesis of stereospecific biomimetic material systems as well as develops an advanced candidate for biomimetic oncolytic agents without biosafety risks.

The infection rate of syphilis continues to rise globally, and the difficulty in diagnosis of neurosyphilis promptly needs to be resolved. More specific and sensitive diagnostic markers for latent syphilis and neurosyphilis should be found. Here the metabolic profiles of 88 cerebrospinal fluid samples from syphilis patients and controls were analyzed by LC/MS-based untargeted metabolomics. In total, 272 metabolites based on 3937 features obtained in ESI- mode and 252 metabolites based on 3799 features in ESI+ mode were identified. The experimental process was evaluated by principal component analysis, partial least squares discriminant analysis, and hierarchical cluster analysis. A clear separation between latent syphilis and neurosyphilis was found. Levels of lipid and linoleic acid metabolites, such as 9-oxo-octadecadienoic acid and 9,10,13-trihydroxyoctadecenoic acid, were increased in syphilis patients. In patients with neurosyphilis, significant changes in levels of 5-hydroxy-L-tryptophan (5-HTP) and acetyl- N -formyl-5-methoxykynurenamine (AFMK) in the tryptophan-kynurenine pathway were also detected. Only one metabolite, theophylline, differed significantly between symptomatic and asymptomatic neurosyphilis patients. Additionally, KEGG analysis revealed significant enrichment of tryptophan metabolism pathways, indicating a high correlation between tryptophan metabolism and syphilis symptoms. Levels of linoleic acid metabolites, 5-HTP, AFMK and theophylline were significantly altered in different patients. The role of these differential metabolites in the development of syphilis is worthy of further exploration. Our results may promote the development of biomarkers for diagnosis of latent syphilis from neurosyphilis, and for that of asymptomatic neurosyphilis from symptomatic neurosyphilis in the future.

Fibrinogen plays an important role in tumor progression. Here, we explored the role of fibrinogen in gallbladder cancer (GBC) metastasis. The plasma fibrinogen level in M1 GBC patients was higher than in M0 GBC patients, indicating that fibrinogen may participate in GBC metastasis. Treatment of GBC cell lines with fibrinogen promoted metastasis and induced the expression of intercellular adhesion molecule 1 (ICAM1). ICAM1 overexpression promoted metastasis and knockdown inhibited it. The cell adhesion and transendothelial migration of GBC cells were enhanced by fibrinogen treatment and ICAM1 overexpression. In addition, the medium of fibrinogen-treated and overexpression-ICAM1 NOZ cells exhibited enhanced macrophages recruitment. This may work in concert to promote angiogenesis. Immunohistochemistry results on clinical specimens showed that higher fibrinogen levels, higher ICAM1 expression, higher blood vessel density, and higher macrophage levels were present simultaneously. Collectively, this study indicates fibrinogen promotes metastasis and extravasation by inducing ICAM1 expression to enhance tumor cell migration, cell adhesion, transendothelial migration and promote angiogenesis and increase vascular endothelial permeability., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

SARS-CoV and SARS-CoV-2 have been thought to originate from bats. In this study, we screened pharyngeal and anal swabs from 13 064 bats collected between 2016 and 2021 at 703 locations across China for sarbecoviruses, covering almost all known southern hotspots, and found 146 new bat sarbecoviruses. Phylogenetic analyses of all available sarbecoviruses show that there are three different lineages-L1 as SARS-CoV-related CoVs (SARSr-CoVs), L2 as SARS-CoV-2-related CoVs (SC2r-CoVs) and novel L-R (recombinants of L1 and L2)-present in Rhinolophus pusillus bats, in the mainland of China. Among the 146 sequences, only four are L-Rs. Importantly, none belong in the L2 lineage, indicating that circulation of SC2r-CoVs in China might be very limited. All remaining 142 sequences belong in the L1 lineage, of which YN2020B-G shares the highest overall sequence identity with SARS-CoV (95.8%). The observation suggests endemic circulations of SARSr-CoVs, but not SC2r-CoVs, in bats in China. Geographic analysis of the collection sites in this study, together with all published reports, indicates that SC2r-CoVs may be mainly present in bats of Southeast Asia, including the southern border of Yunnan province, but absent in all other regions within China. In contrast, SARSr-CoVs appear to have broader geographic distribution, with the highest genetic diversity and sequence identity to human sarbecoviruses along the southwest border of China. Our data provide the rationale for further extensive surveys in broader geographical regions within, and beyond, Southeast Asia in order to find the most recent ancestors of human sarbecoviruses., (© The Author(s) 2022. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Background: To evaluate the efficacy and safety of the Rotarex mechanical thrombectomy device in treating acute lower extremity arterial ischemia and to explore the appropriate indication of the Rotarex device., Methods: A retrospective analysis was performed in 186 patients with acute lower extremity arterial ischemia treated with the Rotarex mechanical thrombectomy device from April 2015 to March 2020 in three vascular surgery centers of Tianjin. As per the comprehensive judgment of the etiology, onset time, imaging of ultrasonography (US) and angiography, and findings during treatment, the patients were divided into the embolization group (69 cases), thrombosis group (primary artery stenosis with thrombosis; 86 cases), and restenosis group (stent restenosis with thrombosis; 31 cases). The primary study outcomes included the success rate of Rotarex mechanical thrombectomy device alone, percutaneous transluminal angioplasty (PTA), stent, catheter-directed thrombolysis (CDT) auxiliary rate, target vessel patency rate, and freedom from clinically driven target lesion revascularization rate (f-CD-TLR). The secondary study outcomes included intraoperative distal arterial embolization, postoperative 30-day bleeding, and deterioration of renal function, amputation, and mortality., Results: The success rate of Rotarex mechanical thrombectomy device alone in the embolization group (44.93%) was significantly higher than that in the thrombosis group (13.95%) and restenosis group (0%) (P < 0.01). The PTA auxiliary rate in the embolization group (26.09%) was significantly lower than that in the thrombosis group (72.09%) and restenosis group (100%) (P < 0.01). The stent implantation rates in the embolization group and restenosis group (11.60% and 33.30%, respectively) were significantly lower than that in the thrombosis group (72.09%) (P < 0.01). There were no significant differences in the CDT auxiliary rate, distal arterial embolization, hemorrhage, renal function deterioration, amputation rate, and mortality among the three groups (P > 0.05). The primary patency at 3 months, 6 months, and 12 months postoperatively was 98.6%, 98.6%, and 84.3% in the embolization group, 96.4%, 89.5%, and 74.9% in the thrombosis group, and 93.2%, 84.7%, and 67.5% in the restenosis group, respectively (P < 0.01). The f-CD-TLR at 12 months postoperatively was 88.9% in the embolization group, which was higher than 77.8% in the thrombosis group and 67.5% in the restenosis group (P < 0.01)., Conclusions: The Rotarex mechanical thrombectomy device is a minimally invasive, safe, and effective treatment option for acute lower extremity arterial ischemia, particularly acute arterial embolization. For acute thrombosis secondary to primary artery stenosis and in-stent restenosis, Rotarex device can effectively reduce the thrombus burden and create favorable conditions for other concurrent interventions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Neutrophils have been recognized to play an important role in the pathogenesis of tuberculosis in recent years. Interferon-induced blood transcriptional signatures in ATB are predominantly driven by neutrophils. In this study, we performed global RNA-seq on peripheral blood neutrophils from active tuberculosis patients (ATB, n=15); latent tuberculosis infections (LTBI, n=22); and healthy controls (HC, n=21). The results showed that greater perturbations of gene expression patterns happened in neutrophils from ATB individuals than HC or those with LTBI, and a total of 344 differentially expressed genes (DEGs) were observed. Functional enrichment analysis showed that besides the interferon signaling pathway, multiple pattern recognition receptor pathways were significantly activated in ATB, such as NOD-like receptors and Toll-like receptors. Meanwhile, we also observed that the expression of genes related to endocytosis, secretory granules, and neutrophils degranulation were downregulated. Our data also showed that the NF-κB signaling pathway might be inhibited in patients with ATB, which could increase Mycobacterium tuberculosis survival and lead to active tuberculosis status. Furthermore, we validated the accuracy of some differentially expressed genes in an independent cohort using quantitative PCR, and obtained three novel genes ( RBM3, CSRNP1, SRSF5 ) with the ability to discriminate active tuberculosis from LTBI and HC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Geng, Wu, Yang, Xin, Zhang, Wang, Liu, Liu, Chen, Liu, Zhang, Pan, Zhang, Gao and Jin.)

Background: Open enucleation (OE) is often performed for giant liver hemangioma (LH) because of its advantage in maximum preservation of functional liver parenchyma. Laparoscopic enucleation (LE) has been applied to LHs more frequently for its potential advantages in postoperative recovery and blood loss. However, to date, LE is still a difficult and complex surgical technique especially when the hemangioma is located in the right hemi liver. The aim of this study was to analyze whether LE is superior to OE for LH in the right hemi liver., Methods: Demographics and perioperative data of patients who underwent LE or OE for LH in the right hemi liver between May 2013 and July 2020 were collected. To decrease the selection bias, patients who underwent OE in first 2 years and those underwent LE in next 5 years by a same operation team were included. The data of sex, age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, largest tumor size, and removed tumor number were enrolled in the propensity score matching (PSM) method to compensate for differences in the baseline characteristics between LE and OE groups. The perioperative outcomes were compared between 2 matched groups after PSM method., Results: A total of 110 patients (36 LE vs. 74 OE) were matched by age, sex, BMI, ASA grade score, largest tumor size, removed tumor number and tumor location. Finally, 34 patients in each group were retained after PSM. There were no significant differences in operative time, estimated blood loss, amount of autologous transfusion, morbidity grade and the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) on postoperative day 1 or 3 or 5. LE was associated with a significantly higher rate of use of the Pringle maneuver (P<0.001), shorter time to oral feeding (P<0.001) and shorter postoperative length of stay (P<0.001)., Conclusions: For LHs in the right hemi liver, the perioperative safety of LE is not inferior to OE, and LE seems to achieves a faster recovery from surgery compared with OE., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3074/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Posttranslational modifications (PTMs) could influence many aspects of protein behavior and function in organisms. Protein glycosylation is one of the major PTMs observed in bacteria, which is crucial for functional regulations of many prokaryotic and eukaryotic organisms. Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine has been recognized as an indispensable tool in the global fight against tuberculosis (TB) worldwide over several decades. Nevertheless, analysis of glycoprotein profiles of BCG has not been clearly investigated. In this study, we performed O-mannosylated protein analysis in BCG bacteria using gel-based and gel-free approaches. In total, 1,670 hexosylated peptides derived from 754 mannosylated proteins were identified. Furthermore, 20 novel protein products supported by 78 unique peptides not annotated in the BCG database were detected. Additionally, the translational start sites of 384 proteins were confirmed, and 78 proteins were validated through the extension of translational start sites based on N-terminus-derived peptides. The bioinformatic analysis of the O-mannosylated proteins was performed and the expression profiles of four randomly selected proteins were validated through Western blotting. A number of proteins involved in metabolic pathways, including the tricarboxylic acid cycle, glycolysis, oxidative phosphorylation, and two-component system, are discussed. Taken together, these results offer the first O-mannosylated protein analysis of a member of mycobacteria reported to date by using complementary gel-based and gel-free approaches. Some of the proteins identified in this study have important roles involved in metabolic pathways, which could provide insight into the immune molecular mechanisms of this recognized vaccine strain., (© 2021 International Union of Biochemistry and Molecular Biology.)

The extracellular contractile injection systems (eCISs) are encoded in the genomes of a large number of bacteria and archaea. We have previously characterized the overall structure of Photorhabdus Virulence Cassette (PVC), a typical member of the eCIS family. PVC resembles the contractile tail of bacteriophages and exerts its action by the contraction of outer sheath and injection of inner tube plus central spike. Nevertheless, the biological function of PVC effectors and the mechanism of effector translocation are still lacking. By combining cryo-electron microscopy and functional experiments, here we show that the PVC effectors Pdp1 (a new family of widespread dNTP pyrophosphatase effector in eCIS) and Pnf (a deamidase effector) are loaded inside the inner tube lumen in a "Peas in the Pod" mode. Moreover, we observe that Pdp1 and Pnf can be directly injected into J774A.1 murine macrophage and kill the target cells by disrupting the dNTP pools and actin cytoskeleton formation, respectively. Our results provide direct evidence of how PVC cargoes are loaded and delivered directly into mammalian macrophages., (© 2021. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To provide available quantitative evidence of efficacy and safety of acupuncture treatments for improving sacroiliac joint malposition., Methods: Databases such as the China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (CQVIP), Wanfang Database (Wanfang), China Biology Medicine disc (CBMdisc), PubMed, Web of Science, EMBASE, and Cochrane Library were searched by computer to collect the reports on acupuncture treatment of sacroiliac joint malposition from the database creation to July 20, 2021. The selection of included studies, data extraction and coding, and bias risk assessment were conducted independently by two reviewers. RevMan5.4 software was used for meta-analysis, and the results were expressed as mean difference (MD) or standardized mean difference (SMD), with a confidence interval (CI) of 95%., Results: A total of 10 randomized controlled clinical trials (RCTs) with 1019 participants were included. Their overall quality of methodology was not high, and there may be publication bias. Meta-analysis showed that the total effective rate of the treatment group was higher than that of the control group (OR = 2.74, 95% CI 2.00 to 3.74, P < 0.00001). The treatment group was better than the control group in improving VAS score (WMD = -1.56, 95% CI -2.18 to -0.94, P < 0.00001). The ODI score of the treatment group was lower than that of the control group (WMD = -6.04, 95% CI -7.05 to -5.02, P < 0.00001). With the improvement of the JOA score, the difference of iliac transverse diameter of sacroiliac joint dislocation and the index of sacroiliac joint malposition in the treatment group were better than those in the control group ( P < 0.05). There was no significant heterogeneity among the studies., Conclusion: Acupuncture may have therapeutic advantages in improving sacroiliac joint malposition. Acupuncture and acupotomy provide a safe way to improve the related clinical symptoms and functional disorders in activity of sacroiliac joint dislocation. However, due to the low quality of the included literature, this conclusion still needs to be further verified by more high-quality and large-sample RCTs., Competing Interests: All authors declare that they have no conflicts of interest., (Copyright © 2022 Liguo Liu et al.)

Photorhabdus is a Gram-negative bacterium from the family Enterobacteriaceae that lives in a symbiotic association with nematode or insects. In addition to the role of being insect pathogens, one species called Photorhabdus asymbiotica (Pa) causes human infection around the world. Nevertheless, how does this transkingdom infection occur remains elusive. Here we focus on one pathogenic determinant called Photorhabdus virulence cassette (PVC) that is founded in the Pa genome and many other pathogens. The RNA-seq and qPCR data showed that the NF-κB and MAPK pathways were drastically activated in the PVC-treated mammalian macrophages. Western blotting assays using samples treated with various inhibitors of the affected pathways confirmed the results we have observed for MAPK pathway previously. p65 translocation assays validated the NF-κB activation in the macrophages after PVC treatment. Moreover, the bacterial phagocytosis by macrophage was also promoted by PVC at the early stage, and this phagocytosis was inhibited by cytoskeleton inhibitors. Thus, the results indicated that PVC is involved in the bacterial invasion by activating NF-κB and MAPK signaling pathway, providing a new perspective for analyzing the pathogenicity of Pa in human infections.

Background & Aims: Our previous genomic whole-exome sequencing (WES) data identified the key ErbB pathway mutations that play an essential role in regulating the malignancy of gallbladder cancer (GBC). Herein, we tested the hypothesis that individual cellular components of the tumor microenvironment (TME) in GBC function differentially to participate in ErbB pathway mutation-dependent tumor progression., Methods: We engaged single-cell RNA-sequencing to reveal transcriptomic heterogeneity and intercellular crosstalk from 13 human GBCs and adjacent normal tissues. In addition, we performed WES analysis to reveal the genomic variations related to tumor malignancy. A variety of bulk RNA-sequencing, immunohistochemical staining, immunofluorescence staining and functional experiments were employed to study the difference between tissues with or without ErbB pathway mutations., Results: We identified 16 cell types from a total of 114,927 cells, in which epithelial cells, M2 macrophages, and regulatory T cells were predominant in tumors with ErbB pathway mutations. Furthermore, epithelial cell subtype 1, 2 and 3 were mainly found in adenocarcinoma and subtype 4 was present in adenosquamous carcinoma. The tumors with ErbB pathway mutations harbored larger populations of epithelial cell subtype 1 and 2, and expressed higher levels of secreted midkine (MDK) than tumors without ErbB pathway mutations. Increased MDK resulted in an interaction with its receptor LRP1, which is expressed by tumor-infiltrating macrophages, and promoted immunosuppressive macrophage differentiation. Moreover, the crosstalk between macrophage-secreted CXCL10 and its receptor CXCR3 on regulatory T cells was induced in GBC with ErbB pathway mutations. Elevated MDK was correlated with poor overall survival in patients with GBC., Conclusions: This study has provided valuable insights into transcriptomic heterogeneity and the global cellular network in the TME, which coordinately functions to promote the progression of GBC with ErbB pathway mutations; thus, unveiling novel cellular and molecular targets for cancer therapy., Lay Summary: We employed single-cell RNA-sequencing and functional assays to uncover the transcriptomic heterogeneity and intercellular crosstalk present in gallbladder cancer. We found that ErbB pathway mutations reduced anti-cancer immunity and led to cancer development. ErbB pathway mutations resulted in immunosuppressive macrophage differentiation and regulatory T cell activation, explaining the reduced anti-cancer immunity and worse overall survival observed in patients with these mutations., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objectives: The scope of laparoscopic surgery has expanded to encompass hepatic resections, specifically hepatic hemangioma. The most serious intraoperative complication is bleeding, often requiring laparotomy. Because risk factors associated with such massive blood loss have not been well evaluated, the intent of this retrospective study was to analyze these risk factors associated with laparoscopic resection of hepatic hemangiomas., Methods: From June 1, 2011 to January 31, 2021, 140 consecutive patients underwent laparoscopic surgery for hepatic hemangioma in our hospital. According to quantity of intraoperative blood loss, they were divided into massive (≥ 800 ml) and minor blood loss (< 800 ml) groups. Perioperative data were analyzed by univariate and multivariate analyses with logistic regression to identify the risk factors for potential massive blood loss during laparoscopic resection., Results: There were 24 and 116 patients in the massive and minor blood loss groups, respectively. Of four risk factors significantly associated with massive blood loss by univariate logistic regression analysis (location of hemangioma in the liver, postcaval or hepatic venous compression, hilar compression, and body mass index exceeding 28) the multifactorial logistic model identified only location in the liver of the hemangioma as statistically (P = 0.012) associated with intraoperative massive blood loss., Conclusions: Location of the hepatic hemangioma was the single statistically significant risk factor for massive blood loss during laparoscopic surgery for hepatic hemangioma. Of particular importance, location in Couinaud liver segments I, IVa, VII, and VIII necessitates precautions to mitigate the risk of massive blood loss., Competing Interests: Conflict of interests: none., (© 2021 by SLS, Society of Laparoscopic & Robotic Surgeons.)

Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is one of the primary causes of death worldwide. Rapid and accurate diagnosis of TB is one of the most direct means to reduce the incidence of TB. In this study, urinary proteomic profiling of TB patients and non-TB individual controls (HCs) was performed, and differentially expressed urinary proteins between TB and HCs were compared and exclusively expressed proteins in TB patients were selected to establish a clinically useful disease marker panel. In total, these top 11 targeted proteins with 265 peptides were scheduled for multiple reaction monitoring validation analysis by using urine samples from 52 TB patients and 52 HCs. The result demonstrated that a three-protein combination out of the five-protein panel (namely P22352, Q9P121, P15151, Q13291, and Q8NDA2) exhibited sensitivity rate of 82.7% in the diagnosis of TB. Furthermore, the three-protein combination could differentiate TB from the latent tuberculosis (LTB) effectively, which exhibited specificity rate of 92.3% for the diagnosis of TB from the LTB category. Although more numbers of clinical samples are required for further verification, the results provided preliminary evidence that this "three-protein combination" out of the five-protein panel could probably be a novel TB diagnostic biomarker in clinical application., (© 2021 International Union of Biochemistry and Molecular Biology.)

Dysfunction of Sirtuin 3 (SIRT3), an NAD + -dependent histone deacetylase, impairs varied mitochondrial metabolic pathways in human cancer. Here, we explored suppressive activity of SIRT3 in the progression of gallbladder cancer (GBC). Expression levels of SIRT3 in patients with GBC were lower than those in the adjacent normal tissue. In addition, decreased expression of SIRT3 in these patients was correlated with poor overall survival. Knockdown of SIRT3 gene in GBC cell lines induced mitochondrial respiration and energy metabolism, but inhibited oxidative ROS. Silence of SIRT3 gene also suppressed AKT-dependent ferroptosis, an iron-dependent and lipid peroxide-mediated cell death. Blockade of AKT activity in sh-SIRT3 cells induced ACSL4 expression that drives ferroptosis, and inhibited epithelial-mesenchymal (EMT) markers and invasive activity. In contrast, overexpression of SIRT3 led to the opposite effects on mitochondrial metabolism and EMT. Finally, transplantation of sh-SIRT3 cells in nude mice resulted in rapid tumor growth and larger tumors that expressed lower E-cadherin and lipid peroxide 4-hydroxynonenal (4-HNE) than those observed in control tumors. Collectively, our studies indicate that SIRT3 functions to inhibit AKT-dependent mitochondrial metabolism and EMT, leading to ferroptosis and tumor suppression., (Copyright © 2021. Published by Elsevier B.V.)

Tuberculosis (TB) is a serious infectious disease with high infection and mortality rates. 5%-10% of the latent tuberculosis infections (LTBI) are likely to develop into active TB, and there are currently no clinical biomarkers that can distinguish between LTBI, active TB and other non-tuberculosis populations. Therefore, it is necessary to develop rapid diagnostic methods for active TB and LTBI. In this study, urinary metabolome of 30 active TB samples and the same number of LTBI and non-TB control samples were identified and analyzed by UPLC-Q Exactive MS. In total, 3744 metabolite components were obtained in ESI- mode and 4086 in ESI + mode. Orthogonal partial least square discriminant analysis (OPLS-DA) and hierarchical cluster analysis (HCA) showed that there were significant differences among LTBI, active TB and non-TB. Six differential metabolites were screened in positive and negative mode, 3-hexenoic acid, glutathione (GSH), glycochenodeoxycholate-3-sulfate, N-[4'-hydroxy-(E)-cinnamoyl]-l-aspartic acid, deoxyribose 5-phosphate and histamine. The overlapping pathways differential metabolites involved were mainly related to immune regulation and urea cycle. The results showed that the urine metabolism of TB patients was disordered and many metabolic pathways changed. Multivariate statistical analysis revealed that GSH and histamine were selected as potential molecular markers, with area under curve of receiver operating characteristic curve over 0.75. Among the multiple differential metabolites, GSH and histamine changed to varying degrees in active TB, LTBI and the non-TB control group. The levels of GSH and histamine in 48 urinary samples were measured by ELISA in validation phase, and the result in our study provided the potential for non-invasive biomarkers of TB., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Rac GTPase activating protein 1 (RACGAP1) has been characterized in the pathogenesis and progression of several malignancies, however, little is known regarding its role in the development of gallbladder cancer (GBC). This investigation seeks to describe the role of RACGAP1 and its associated molecular mechanisms in GBC. It was found that RACGAP1 was highly expressed in human GBC tissues, which was associated to poorer overall survival (OS). Gene knockdown of RACGAP1 hindered tumor cell proliferation and survival both in vitro and in vivo . We further identified that RACGAP1 was involved in DNA repair through its binding with DNA ligase 3 (LIG3), a crucial component of the alternative-non-homologous end joining (Alt-NHEJ) pathway. RACGAP1 regulated LIG3 expression independent of RhoA activity. RACGAP1 knockdown resulted in LIG3-dependent repair dysfunction, accumulated DNA damage and Poly(ADP-ribosyl) modification (PARylation) enhancement, leading to increased apoptosis and suppressed cell growth. We conclude that RACGAP1 exerts a tumor-promoting role via binding LIG3 to reduce apoptosis and facilitate cell growth in GBC, pointing to RACGAP1 as a potential therapeutic target for GBC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)