Search

ATP-binding cassette transporter B6 (ABCB6), a protein essential for heme biosynthesis in mitochondria, also functions as a heavy metal efflux pump. Here, we present cryo-electron microscopy structures of human ABCB6 bound to a cadmium Cd(II) ion in the presence of antioxidant thiol peptides glutathione (GSH) and phytochelatin 2 (PC2) at resolutions of 3.2 and 3.1 Å, respectively. The overall folding of the two structures resembles the inward-facing apo state but with less separation between the two halves of the transporter. Two GSH molecules are symmetrically bound to the Cd(II) ion in a bent conformation, with the central cysteine protruding towards the metal. The N-terminal glutamate and C-terminal glycine of GSH do not directly interact with Cd(II) but contribute to neutralizing positive charges of the binding cavity by forming hydrogen bonds and van der Waals interactions with nearby residues. In the presence of PC2, Cd(II) binding to ABCB6 is similar to that observed with GSH, except that two cysteine residues of each PC2 molecule participate in Cd(II) coordination to form a tetrathiolate. Structural comparison of human ABCB6 and its homologous Atm-type transporters indicate that their distinct substrate specificity might be attributed to variations in the capping residues situated at the top of the substrate-binding cavity., (© 2024. The Author(s).)

Background: Pyroptosis plays a crucial role in immune responses. However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear. Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978). Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS. Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation. PRS, composed of four pyroptosis-related differentially expressed genes ( BATF2 , PTPRJ , RGS1 , and VCAN ), is a reliable and independent biomarker for GC. PRS low is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center. Importantly, PRS low marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy. Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment. A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Converting CO 2 into valuable chemicals via sustainable energy sources is indispensable for human development. Photothermal catalysis combines the high selectivity of photocatalysis and the high yield of thermal catalysis, which is promising for CO 2 reduction. However, the present photothermal catalysts suffer from low activity due to their poor light absorption ability and fast recombination of photogenerated electrons and holes. Here, a TiO 2 @Bi 2 WO 6 heterojunction photocatalyst featuring a hierarchical hollow structure was prepared by an in situ growth method. The visible light absorption and photothermal effect of the TiO 2 @Bi 2 WO 6 photocatalyst is promoted by a hierarchical hollow structure, while the recombination phenomenon is significantly mitigated due to the construction of the heterojunction interface and the existence of excited Bi (3- x )+ sites. Such a catalyst exhibits excellent photothermal performance with a CO yield of 43.7 μmol h -1 g -1 , which is 15 and 4.7 times higher than that of pure Bi 2 WO 6 and that of physically mixed TiO 2 /Bi 2 WO 6 , respectively. An in situ study shows that the pathway for the transformation of CO 2 into CO over our TiO 2 @Bi 2 WO 6 proceeds via two important intermediates, including COO - and COOH - . Our work provides a new idea of excited states for the design and synthesis of highly efficient photothermal catalysts for CO 2 conversion.

Modern semiconductor fabrication is challenged by difficulties in overcoming physical and chemical constraints. A major challenge is the wet etching of dummy gate silicon, which involves the removal of materials inside confined spaces of a few nanometers. These chemical processes are significantly different in the nanoscale and bulk. Previously, electrical double-layer formation, bubble entrapment, poor wettability, and insoluble intermediate precipitation have been proposed. However, the exact suppression mechanisms remain unclear due to the lack of direct observation methods. Herein, we investigate limiting factors for the etching kinetics of silicon with tetramethylammonium hydroxide at the nanoscale by using liquid-phase transmission electron microscopy, three-dimensional electron tomography, and first-principles calculations. We reveal suppressed chemical reactions, unstripping phenomena, and stochastic etching behaviors that have never been observed on a macroscopic scale. We expect that solutions can be suggested from this comprehensive insight into the scale-dependent limiting factors of fabrication.

Objective: To analyze the effect of recombinant human thrombopoietin (rhTPO) on platelet (PLT) reconstitution after autologous peripheral blood stem cell transplantation (APBSCT) in patients with multiple myeloma (MM)., Methods: The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed. According to whether rhTPO was used during APBSCT, the patients were divided into rhTPO group (80 cases) and control group (67 cases). The time of PLT engraftment, blood product infusion requirements, the proportion of patients with PLT recovery to≥50×10 9 /L and≥100×10 9 /L at +14 days and +100 days after transplantation, and adverse reactions including the incidence of bleeding were compared between the two groups., Results: There were no significant differences between the two groups in sex, age, M protein type, PLT count at the initial diagnosis, median duration of induction therapy before APBSCT, and number of CD34 + cells reinfused (all P >0.05). The median time of PLT engraftment in the rhTPO group was 10 (6-14) days, which was shorter than 11 (8-23) days in the control group ( P < 0.001). The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U, which was less than 20 (0-80)U in the control group ( P =0.001). At +14 days after transplantation, the proportions of patients with PLT≥50×10 9 /L in the rhTPO group and the control group were 66.3% and 52.2%, while the proportions of patients with PLT≥100×10 9 /L were 23.8% and 11.9%, respectively, with no significant differences (all P >0.05). At +100 days after transplantation, the proportion of patients with PLT≥50×10 9 /L in rhTPO group and control group was 96.3% and 89.6%, respectively ( P >0.05), but the proportion of patients with PLT≥100×10 9 /L in rhTPO group was higher than that in control group (75.0% vs 55.2%, P =0.012). There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups. In rhTPO group, the rhTPO administration was well tolerated, and the incidences of abnormal liver and kidney function and infection were similar to those in the control group., Conclusion: When MM patients undergo first-line APBSCT, subcutaneous injection of rhTPO can shorten the time of platelet engraftment, reduce the transfusion volume of blood products, and be well tolerated, moreover, more patients have achieve a high level of PLT recovery after transplantation, which is very important for ensuring the safety of APBSCT and maintenance therapy.

Primary gastrointestinal (GI) T-cell and natural killer (NK)-cell lymphomas/lymphoproliferative disorders (LPD) are uncommon, and they are usually aggressive in nature. However, T-cell and NK-cell lymphoma/LPD of the GI tract with indolent clinical course has been reported over the past 2 decades. Indolent T-cell LPD was formally proposed a decade ago in 2013 and 4 years later recognized as a provisional entity by the revised fourth edition of WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues in 2017. Indolent T-cell LPD of the GI tract has been changed to indolent T-cell lymphoma of the GI tract as a distinct entity by the fifth edition of WHO Classification of Haematolymphoid Tumours, but the International Consensus Classification of mature lymphoid neoplasms prefers indolent clonal T-cell LPD of the GI tract instead. In the past decade, indolent lymphoma/LPD of the GI tract has been expanded to NK cells, and as such, indolent NK-cell LPD of the GI tract was recognized as an entity by both the fifth edition of WHO Classification of Haematolymphoid Tumours and the International Consensus Classification. The underlying genetic/molecular mechanisms of both indolent T-cell lymphoma/LPD of the GI tract and indolent NK-cell LPD of the GI tract have been recently discovered. In this review, we describe the history; salient clinical, cytohistomorphologic, and immunohistochemical features; and genetic/genomic landscape of both entities. In addition, we also summarize the mimics and differential diagnosis. Finally, we propose future directions with regard to the pathogenesis and clinical management., (Published by Elsevier Inc.)

Purpose: Despite technological and immunologic innovations, some living-donor liver transplant (LDLT) recipients still face poor liver regeneration. Sarcopenia is often recognized as a biomarker for poor outcomes in surgical patients. This study aimed to evaluate associations between sarcopenia and liver regeneration in LDLT recipients., Materials and Methods: This retrospective review included consecutive patients who had received LDLT at Chang Gung Memorial Hospital between 2005 and 2017. Sarcopenia was assessed using the psoas muscle index (PMI) in cross-sectional images. Receiver operating characteristic curve analysis was used to determine the ability of PMI to predict relatively poor survival rates. Correlations between liver regeneration and sarcopenia were evaluated using regression analysis., Results: A total of 109 LDLT recipients were included. The 1-, 3-, 5, 10-, and 15-year survival rates were 93.7%, 84.8%, 79.7%, 74.7%, and 73.3% in males and 93.3%, 83.3%, 83.3%, 71.4%, and 71.4% in females. PMIs were significantly different based on 10- and 15-year overall survival rates (P = .001 and P = .000) in male patients. Receiver operating characteristic curve analysis revealed the PMI cutoff point at 6.7 cm 2 /m 2 (sensitivity = 48.3%, specificity = 81%, AUC (area under the ROC curve) = 0.685) based on 10-year survival. Linear regression analysis revealed that PMI was significantly associated with liver regeneration in males (P = .013)., Conclusions: Sarcopenia and low PMI are associated with poor liver regeneration and long-term survival after LDLT in male patients. Further studies, including sarcopenia with conventional scores, may help to more reliably predict liver regeneration and mortality among LDLT patients with hepatocellular carcinoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To compare the effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) with different particle sizes in bridging and downstaging in pretransplant hepatocellular carcinoma patients. Assess the recurrent and survival rates after living donor liver transplantation (LDLT)., Methods: Retrospective review of 580 patients who underwent TACE using DEB from August 2012 to June 2020 at Taiwan Kaohsiung Chang Gung Memorial Hospital. Pre- and post-TACE computed tomography scan images of the liver were reviewed, and treatment responses were assessed using modified Response Evaluation Criteria in Solid Tumors criteria. Patients were divided by who met the criteria (n = 342) or beyond (n = 238) the University of California San Francisco criteria for successful bridging and downstaging rate evaluation. Each group was divided into subgroups according to DEB particle sizes (group A: <100μm, group B: 100-300 μm, group C: 300-500 μm, and group D: 500-700 μm) to compare objective response rate and post-LDLT survival rate., Results: Overall successful bridging and downstaging rate is 97.1% and 58.4%, respectively, in the group of patients who meet the criteria (n = 332) and are beyond (n = 139) the University of California San Francisco criteria. Group B (100-300 μm) had a higher successful bridging rate (99.5%, P = .003) and downstaging rate (63.8%, P = .443). This subgroup also demonstrated a higher objective response rate in single (93.2%, P = .038) tumors, multiple (83.3%, P = .001) tumors, and tumors with size less than 5 cm (93.9%, P = .005). There are no significant differences in post-LDLT overall survival rate between different particle sizes., Conclusion: TACE with 100 to 300 μm DEB particles is associated with a better chance of bridging and downstaging hepatocellular carcinoma patients to LDLT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Evaluation of the insulating properties of polymers, such as the dielectric constant and dissipation factor, is crucial in electronic devices, including field-effect transistors and wireless communication applications. This study applies density functional theory (DFT) to predict the dielectric constant of soluble polyimides (SPIs). Various SPIs containing trifluoromethyl groups in the backbone with different pendant types, numbers, and symmetries are successfully synthesized, and their dielectric constants are evaluated and compared with the DFT-estimated values. Two types of DFT-optimized SPIs, single-chain and stacked-chain models, are used to describe the local geometries of the SPIs. In addition, to reveal the relationship between the molecular structure and dielectric constant, further investigations are conducted by considering the dielectric constant of composing ionic and electronic components. The DFT-estimated static dielectric constant of the single-chain model accurately reproduces the corresponding experimental value with at least 80% accuracy. Our approach provides a rational and accelerated strategy to evaluate polymer insulators for electronic devices based on cost-effective DFT calculations.

It is well established that neutrophils adopt malleable polymorphonuclear shapes to migrate through narrow interstitial tissue spaces 1-3 . However, how polymorphonuclear structures are assembled remains unknown 4 . Here we show that in neutrophil progenitors, halting loop extrusion-a motor-powered process that generates DNA loops by pulling in chromatin 5 -leads to the assembly of polymorphonuclear genomes. Specifically, we found that in mononuclear neutrophil progenitors, acute depletion of the loop-extrusion loading factor nipped-B-like protein (NIPBL) induced the assembly of horseshoe, banded, ringed and hypersegmented nuclear structures and led to a reduction in nuclear volume, mirroring what is observed during the differentiation of neutrophils. Depletion of NIPBL also induced cell-cycle arrest, activated a neutrophil-specific gene program and conditioned a loss of interactions across topologically associating domains to generate a chromatin architecture that resembled that of differentiated neutrophils. Removing NIPBL resulted in enrichment for mega-loops and interchromosomal hubs that contain genes associated with neutrophil-specific enhancer repertoires and an inflammatory gene program. On the basis of these observations, we propose that in neutrophil progenitors, loop-extrusion programs produce lineage-specific chromatin architectures that permit the packing of chromosomes into geometrically confined lobular structures. Our data also provide a blueprint for the assembly of polymorphonuclear structures, and point to the possibility of engineering de novo nuclear shapes to facilitate the migration of effector cells in densely populated tumorigenic environments., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This study aims to explore the pathogenesis of myocardial ischaemia reperfusion injury(MIRI) based on oxidative stress-mediated programmed cell death and the mechanism and targets of Chaihu Sanshen Capsules in treating MIRI via the protein kinase Cβ(PKCβⅡ)/NADPH oxidase 2(NOX2)/reactive oxygen species(ROS) signaling pathway. The rat model of MIRI was established by the ligation of the left anterior descending branch. Rats were randomized into 6 groups: sham group, model group, clinically equivalent-, high-dose Chaihu Sanshen Capsules groups, N-acetylcysteine group, and CGP53353 group. After drug administration for 7 consecutive days, the area of myocardial infarction in each group was measured. The pathological morphology of the myocardial tissue was observed by hematoxylin-eosin(HE) staining. The apoptosis in the myocardial tissue was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL). Enzyme-linked immunosorbent assay(ELISA) was employed to measure the le-vels of indicators of myocardial injury and oxidative stress. The level of ROS was detected by flow cytometry. The protein and mRNA levels of the related proteins in the myocardial tissue were determined by Western blot and real-time quantitative PCR(RT-qPCR), respectively. Compared with the sham group, the model group showed obvious myocardial infarction, myocardial structural disorders, interstitial edema and hemorrhage, presence of a large number of vacuoles, elevated levels of myocardial injury markers, myocardial apoptosis, ROS, and malondialdehyde(MDA), lowered superoxide dismutase(SOD) level, and up-regulated protein and mRNA le-vels of PKCβⅡ, NOX2, cysteinyl aspartate specific proteinase-3(caspase-3), and acyl-CoA synthetase long-chain family member 4(ACSL4) in the myocardial tissue. Compared with the model group, Chaihu Sanshen Capsules reduced the area of myocardial infarction, alleviated the pathological changes in the myocardial tissue, lowered the levels of myocardial injury and oxidative stress indicators and apoptosis, and down-regulated the mRNA and protein levels of PKCβⅡ, NOX2, caspase-3, and ACSL4 in the myocardial tissue. Chaihu Sanshen Capsules can inhibit oxidative stress and programmed cell death(apoptosis, ferroptosis) by regulating the PKCβⅡ/NOX2/ROS signaling pathway, thus mitigating myocardial ischemia reperfusion injury.

Seeking novel high-performance elastocaloric materials with low critical stress plays a crucial role in advancing the development of elastocaloric refrigeration technology. Here, as a first attempt, the elastocaloric effect of TiZrNbAl shape memory alloy at both room temperature and finite temperatures ranging from 245 K to 405 K, is studied systematically. Composition optimization shows that Ti-19Zr-14Nb-1Al (at.%), possessing excellent room-temperature superelasticity with a critical stress of around 100 MPa and a small stress hysteresis of around 70 MPa and outstanding fracture resistance with a compressive strain of 20% and stress of 1.7 GPa, demonstrates a substantial advantage as an elastocaloric refrigerant. At room temperature, a large adiabatic temperature change (ΔTad) of -6.7 K is detected, which is comparable to the highest value reported in the Ti-based alloys. A high elastocaloric cyclic stability, with almost no degradation of ΔTad after 4000 cycles, is observed. Furthermore, the sizeable elastocaloric effect can be steadily expanded from 255 K to 395 K with a temperature window of as large as 140 K. A maximum ΔTad of -7.9 K appears at 355 K. The present work demonstrates a promising potential of TiZrNbAl as a low critical stress and low hysteresis elastocaloric refrigerant.

Excessive emission of CO 2 into the atmosphere has severely impacted the global ecological environment. Converting CO 2 into valuable chemicals and fuels is of great significance for sustainable development. However, low activity and undesirable selectivity often result from the inherent inertness of CO 2 . Herein, K- or/and Zn-modified Fe-based catalysts were prepared by an incipient-wetness impregnation method for CO 2 hydrogenation via a cascade reaction. The results indicate that K species exist as K 2 O while Zn species exist as ZnFe 2 O 4 . In the CO 2 hydrogenation pathway, K 2 O facilitates the adsorption of CO 2 and restrains the adsorption of H 2 , accelerating the transformation of CO 2 into C 2 -C 4 olefins rather than paraffins while Zn species promote the dispersion of Fe species, leading to improved activity. Synergistically, a K- and Zn-modified Fe-based catalyst (2Zn-10K-Fe/Al) shows excellent catalytic CO 2 hydrogenation activity, achieving a CO 2 conversion of 77% which is 1.8 times that (42%) of the unmodified Fe-based catalyst (Fe/Al). Our catalyst also shows a significantly promoted selectivity to C 2 -C 4 olefins of 17% in comparison with the Fe/Al catalyst (0%). It is envisioned that such a binary effect of elements might contribute to the low-cost and industrial production of Fe-based catalysts for selective CO 2 conversion.

BRAF mutations are associated with a small number of hematologic malignancies, including hairy cell leukemia and histiocytic disorders. In addition, BRAF mutations have also been detected in low frequency in other B-cell lymphomas, such as chronic lymphocytic leukemia and diffuse large B-cell lymphoma, but never in mantle cell lymphoma (MCL). We present a case of a 69-year-old female with classic MCL harboring a BRAF N581S mutation. To our knowledge, this is the first reported case of any BRAF mutation in MCL., Competing Interests: The authors declare they have no conflicts of interest. Benjamin M. Heyman received research funding and/or has served as an advisor for Astrazeneca, Beigene, Oncternal Therapeutics, and Epizyme. Michael Y. Choi has received research funding and/or has served as an advisor for Abbvie, Astrazeneca, Geron, Janssen, Protagonist, Beigene, Oncternal, and Prelude., (© 2024 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Objective: This research aims to explore the efficiency and safety of endoscopic combined intrarenal surgery (Micro-ECIRS) composed of micro-percutaneous nephrolithotomy (Micro-perc) and retrograde intrarenal surgery (RIRS) in the Galdakao-modified supine Valdivia (GMSV) position for a single session for the treatment of complex nephrolithiasis in children., Materials and Methods: This study retrospectively reviewed patients aged < 18 years who underwent Micro-ECIRS in the GMSV position for renal stones larger than 2 cm under ultrasound guidance between August 2020 to May 2022 at our institution., Results: A total of 13 patients (8 males and 5 females) received Micro-ECIRS for renal stones under ultrasound guidancewhile adopting the GMSV position. The average stone size was 2.7 cm (range: 2.1-3.7 cm). Among them, 6 patients had left kidney stones, 5 patients had right kidney stones, and 2 patients had bilateral kidney stones. The mean operative time was 70.5 min (range: 54-93 min). The mean hospital stay was 6.4 days (range: 4-9 days). The mean hemoglobin decrease was 8.2 g/L (range: 5.1-12.4 g/L). The total number of kidneys that had complete stone clearance was 8 kidneys at 48 h postoperatively, 11 kidneys at 2 weeks postoperatively, and 14 kidneys at 1 month postoperatively., Conclusion: Our results demonstrate that Micro-ECIRS while patients are in the GMSV position is a safe and effective method for the treatment of complex children nephrolithiasis. However, all children made three hospital visits and received anesthesia three times. Further research is needed to confirm these findings., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Surface defects of metal halide perovskite nanocrystals (PNCs) substantially compromise the optoelectronic performances of the materials and devices via undesired charge recombination. However, those defects, mainly the vacancies, are structurally entangled with each other in the PNC lattice, necessitating a delicately designed strategy for effective passivation. Here, a synergistic metal ion doping and surface ligand exchange strategy is proposed to passivate the surface defects of CsPbBr 3 PNCs with various divalent metal (e.g., Cd 2+ , Zn 2+, and Hg 2+ ) acetate salts and didodecyldimethylammonium (DDA + ) via one-step post-treatment. The addition of metal acetate salts to PNCs is demonstrated to suppress the defect formation energy effectively via the ab initio calculations. The developed PNCs not only have near-unity photoluminescence quantum yield and excellent stability but also show luminance of 1175 cd m -2 , current efficiency of 65.48 cd A -1 , external quantum efficiency of 20.79%, wavelength of 514 nm in optimized PNC light-emitting diodes with Cd 2+ passivator and DDA ligand. The "organic-inorganic" hybrid engineering approach is completely general and can be straightforwardly applied to any combination of quaternary ammonium ligands and source of metal, which will be useful in PNC-based optoelectronic devices such as solar cells, photodetectors, and transistors., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Aedes aegypti, the primary vector responsible for transmitting dengue fever in southern Taiwan, has developed a relatively high resistance to synthetic pyrethroids. It has evolved four amino acid substitutions in the voltage-gated sodium channel (VGSC), namely S996P, V1023G, F1565C, and D1794Y. To unveil the distribution and correlation of VGSC mutations and pyrethroid resistance among different field populations, Ae. aegypti collected from various districts in Kaohsiung and Tainan Cities underwent tests for resistance development against different pyrethroids and frequency of S996P, V1023G, F1565C, and D1794Y substitutions. The adult knockdown assay revealed a relatively high knockdown resistance in the Ae. aegypti populations from Kaohsiung and Tainan against permethrin, cypermethrin, and fenvalerate (averaging >50-fold). Conversely, less resistance was observed against α-cypermethrin, deltamethrin, λ-cyhalothrin, cyfluthrin, and etofenprox (averaging <35-fold). Using Polymerase Chain Reaction/restriction fragment length polymorphism analysis, four mutant haplotypes were identified in these field populations. Notably, the S IA VFD and S IB VFD wild haplotypes were absent. Analysis utilizing IBM SPSS Statistics 20.0 and Spearman's rank correlation coefficient indicated that Haplotype C (P IA GFD), especially P allele, frequency displayed a significant positive correlation with five Type II pyrethroid resistance, while 1023G and 1023G/G exhibited a significant association with permethrin and fevalerate resistance. Conversely, Haplotype E (S IB VCD) negatively correlated with pyrethroid resistance, particularly fenvalerate resistance (-0.776). Haplotype C and E were the most prevalent and widely distributed among the investigated field populations. This prevalence of haplotype C is likely tied to the extensive and excessive use of Type II pyrethroids for dengue control over the past three decades. Given the significant positive correlation, the best-fit lines and R 2 values were established to facilitate the swift prediction of knockdown resistance levels to various pyrethroids based on VGSC mutation frequency. This predictive approach aims to guide insecticide usage and the management of pyrethroid resistance in the field populations of Ae. aegypti in Taiwan., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Near early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare hematologic malignancy, for which second line therapeutic options are limited. T-cell leukemias are also rarely associated with leukemia cutis, which is more often seen in leukemias of myeloid origin. We present the case of an adult male diagnosed with near ETP-ALL, with IDH2 and DNMT3A mutations, suggestive of a myeloid origin, and leukemia cutis. After the patient progressed on hyper-CVAD and nelarabine, we treated him with the BCL-2 inhibitor venetoclax and the hypomethylating agent decitabine. The regimen induced a rapid bone marrow response and resolution of the leukemia cutis., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Author(s).)

The chemokine CCL5 plays a potential role in the occurrence and development of colorectal cancer (CRC). Previous studies have shown that CCL5 directly acts on tumor cells to change tumor metastatic rates. In addition, CCL5 recruits immune cells and immunosuppressive cells into the tumor microenvironment (TME) and reshapes the TME to adapt to tumor growth or increase antitumor immune efficacy, depending on the type of secretory cells releasing CCL5, the cellular function of CCL5 recruitment, and the underlying mechanisms. However, at present, research on the role played by CCL5 in the occurrence and development of CRC is still limited, and whether CCL5 promotes the occurrence and development of CRC and its role remain controversial. This paper discusses the cells recruited by CCL5 in patients with CRC and the specific mechanism of this recruitment, as well as recent clinical studies of CCL5 in patients with CRC.Key MessagesCCL5 plays dual roles in colorectal cancer progression.CCL5 remodels the tumor microenvironment to adapt to colorectal cancer tumor growth by recruiting immunosuppressive cells or by direct action.CCL5 inhibits colorectal cancer tumor growth by recruiting immune cells or by direct action.

The application of DNA barcoding has been significantly limited by the scarcity of reliable specimens and inadequate coverage and replication across all species. The deficiency of DNA barcode reference coverage is particularly striking for highly biodiverse subtropical and tropical regions. In this study, we present a comprehensive barcode library for woody plants in tropical and subtropical China. Our dataset includes a standard barcode library comprising the four most widely used barcodes (rbcL, matK, ITS, and ITS2) for 2,520 species from 4,654 samples across 49 orders, 144 families, and 693 genera, along with 79 samples identified at the genus level. This dataset also provides a super-barcode library consisting of 1,239 samples from 1,139 species, 411 genera, 113 families, and 40 orders. This newly developed library will serve as a valuable resource for DNA barcoding research in tropical and subtropical China and bordering countries, enable more accurate species identification, and contribute to the conservation and management of tropical and subtropical forests., (© 2023. The Author(s).)

(1) Background: A cementless total knee arthroplasty (TKA) is a recent and an increasingly popular innovation that enhances porous fixation surfaces. However, the lack of cemented sealing of an exposed resected bone has raised concerns about the potential for greater blood loss. The goals of this study were to determine if a cementless approach impacts post-TKA hemodynamics and to identify risk factors for blood loss in instances of cementless (vs. cemented) TKAs under a contemporary patient blood management (PBM) protocol. (2) Methods: We recruited 153 consecutive patients undergoing unilateral TKAs between 2019 and 2023. All enrollees received cementless or cemented prostheses of the same design (cementless, 87; cemented, 66). After propensity score matching for demographics, there were 46 patients in each group. We then compared blood loss metrics (total [TBL] and estimated [EBL]), drainage volumes, hemoglobin (Hb) levels, and transfusion rates by group. (3) Results: Post-TKA hemodynamics (i.e., TBL, EBL, drainage, Hb level, and transfusion rate) of cementless (n = 46) and cemented (n = 46) TKA groups did not differ significantly. In addition, the proportions of patients with Hb drops > 3.0 g/dL were similar for the two groups. A logistic regression analysis revealed that only preoperative Hb and EBL during the early postoperative period were predictive of a substantial fall in Hb levels. The fixation method was not associated with Hb decline > 3.0 g/dL by postoperative Day 3. (4) Conclusion: The cementless TKA has no impact on customary post-TKA hemodynamics and is not associated with greater TKA-related blood loss when implementing a contemporary PBM protocol.

Revision repair of retorn partial articular supraspinatus tendon avulsion (PASTA) lesion is difficult for poor tendon quality without tear completion and repair. Trans-tendon suture bridge repair with biceps tendon augmentation can preserve the intact bursal side cuff attachment and has shown satisfactory clinical outcomes. Moreover, trans-tendon suture bridge rotator cuff repair technique, along with biceps tendon augmentation, reinforces high-grade PASTA lesions by moving the tenotomized biceps tendon into the torn articular side cuff defect with added advantage of blood supply through the tenotomized biceps tendon graft. Retear after trans-tendon repair of high-grade PASTA lesions was rare, and its poor tendon quality cause the revision repair to be too difficult. Without tear completion and rotator cuff repair, this arthroscopic trans-tendon suture bridge rotator cuff repair with biceps tendon augmentation is a reliable procedure that could be expected to produce improved short-term functional and radiologic outcomes, along with improved tendon quality of repaired tendon., (© 2023 The Authors.)

Motivation: Precise identification of cancer cells in patient samples is essential for accurate diagnosis and clinical monitoring but has been a significant challenge in machine learning approaches for cancer precision medicine. In most scenarios, training data are only available with disease annotation at the subject or sample level. Traditional approaches separate the classification process into multiple steps that are optimized independently. Recent methods either focus on predicting sample-level diagnosis without identifying individual pathologic cells or are less effective for identifying heterogeneous cancer cell phenotypes., Results: We developed a generalized end-to-end differentiable model, the Cell Scoring Neural Network (CSNN), which takes sample-level training data and predicts the diagnosis of the testing samples and the identity of the diagnostic cells in the sample, simultaneously. The cell-level density differences between samples are linked to the sample diagnosis, which allows the probabilities of individual cells being diagnostic to be calculated using backpropagation. We applied CSNN to two independent clinical flow cytometry datasets for leukemia diagnosis. In both qualitative and quantitative assessments, CSNN outperformed preexisting neural network modeling approaches for both cancer diagnosis and cell-level classification. Post hoc decision trees and 2D dot plots were generated for interpretation of the identified cancer cells, showing that the identified cell phenotypes match the cancer endotypes observed clinically in patient cohorts. Independent data clustering analysis confirmed the identified cancer cell populations., Availability and Implementation: The source code of CSNN and datasets used in the experiments are publicly available on GitHub (http://github.com/erobl/csnn). Raw FCS files can be downloaded from FlowRepository (ID: FR-FCM-Z6YK)., (© The Author(s) 2023. Published by Oxford University Press.)

Two new phenylpropanoids ( 1 and 2 ) and one new isoflavone glycoside ( 3 ), along with nine known compounds ( 4  -  12 ), were isolated from the pod of Ceratonia siliqua L. Their chemical structures were elucidated based on extensive spectroscopic analyses (1 D and 2 D NMR, UV, IR, and HRESIMS) and compared with the literature data. In addition, all isolated compounds were evaluated in vitro for inhibitory activity against acetylcholinesterase (AChE). Compounds 4 , 5 , and 12 showed inhibitory activity against acetylcholinesterase (AChE) with IC 50 values ranging from 15.0 to 50.2 μM.

Vibrio α-hemolysins (αHLs) are β-pore-forming toxins secreted by Vibrio pathogens, crucial for the facilitation of bacterial infections through host cell lysis. These toxins are produced as inactive precursors, requiring proteolytic maturation and membrane association for activation within host tissues. Here, we investigate Vibrio campbellii αHL (VcαHL), and establish that its hemolytic activity is significantly stimulated by calcium ions, with an EC 50 that aligns with physiological calcium concentrations. Furthermore, we illustrate the vital contribution of calcium ions to the oligomerization of VcαHL on membranes. Using X-ray crystallography and cryo-electron microscopy, we decipher both the immature and assembled structures of VcαHL and elucidate the conformational changes corresponding to toxin assembly. We also identify a calcium-binding module that is integral for VcαHL's calcium-dependent activation. These findings provide insights into the regulatory mechanisms of VcαHL and have the potential to inform the development of targeted therapeutic strategies against Vibrio infections., (© 2023. Springer Nature Limited.)

Culicoides-borne viruses are an important arbovirus group causing bovine diseases. During 2012-2019, 2,525 pools consisting of 108,937 specimens of vectors were subjected to PCR detection of bovine arbovirus belonging to Orthobunyavirus, Orbivirus, and Ephemerovirus. Twelve virus RNAs, of which 6, that is, Shuni virus, Shamonda virus, and Sathuperi virus in Orthobunyavirus and Sathuvachari virus and epizootic hemorrhagic disease virus serotypes 4 and 7 in Orbivirus were detected for the first time in the area. Potential vector species were evaluated by the minimum infection rate, and the population abundance of Culicoides oxystoma, Culex tritaeniorhynchus, and Anopheles sinensis indicated that they were the main potential vector species in dairy farms in Taiwan., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America.)

Background and Aims: Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) is the reference standard of hepatic steatosis assessment. This study evaluates usefulness of controlled attenuation parameter (CAP) in monitoring the clinically relevant outcome by MRI-PDFF for non-alcoholic fatty liver disease (NAFLD) patients., Methods: NAFLD patients were enrolled prospectively. Instruction was given in lifestyle modifications with exercise and control of metabolic factors. MRI-PDFF and CAP were performed at enrollment and follow-up, with the diagnostic validity of CAP in monitoring clinically relevant outcome defined as a decline of ≥30% relative to baseline value by MRI-PDFF., Results: A total of 75 patients (male/female: 49/26, mean age: 53.2) were enrolled. Baseline MRI-PDFF, CAP and liver stiffness was 14.4%, 300.2 dB/m and 6.5 kPa. In a median interval of 369 days, thirteen (17.3%) patients achieved clinically relevant outcome with decline of 46.7 dB/m by CAP, compared with increase of 5.1 in the other patients. In multivariate analysis, clinically relevant outcome was associated with changes (Δ) of CAP and glucose. Assessed by area under receiver operating curve, the performances of ΔCAP in predicting clinically relevant outcome were 0.815 and 0.808, and with the specificity of >90%, the ΔCAP cutoff was -46 dB/m and -15% relative to baseline value; sensitivity was 53.8% and 46.2% with negative predictive value of 90.3% and 88.9% respectively., Conclusions: For NAFLD patients, CAP exhibited good performance in monitoring clinically relevant decline of hepatic steatosis in MRI-PDFF. With the cutoffs of -46 dB/m or -15%, ΔCAP is useful in excluding clinical relevant outcome achievement., (© 2023 John Wiley & Sons Ltd.)

Background: It may be difficult for pediatric patients to evaluate the impact of liver transplantation (LT) on splenomegaly due to the natural growth course. The long-term dynamics of portal vein (PV) size and PV flow after LT in pediatric patients are unclear. We aimed to evaluate the long-term transition of the splenic size, PV size, and PV flow velocity in pediatric patients who underwent successful living donor liver transplantation (LDLT) and survived >10 years., Methods: From October 2004 to December 2010, 39 pediatric patients (25 boys; 14 girls) underwent LDLT, received pre-LDLT and post-LDLT computed tomography scans and long-term ultrasound sonography follow-up, and survived >10 years without additional intervention at our institution. We analyzed the short- to mid-term and long-term impact of LDLT on splenic size, PV size, and PV flow velocity over time., Results: The PV diameter increased throughout the 10-year follow-up (P < .001). The PV flow velocity increased 1 day after LDLT (P< .001); proceeded to decrease 3 days after LDLT, reaching a low point 6 to 9 months after LDLT; and remained stable throughout the 10-year follow-up. Regression of the splenic volume at 6 to 9 months after LDLT (P < .001) was noted. However, the splenic size steadily increased on long-term follow-up., Conclusions: Although LDLT has a significant short-term reduction effect on splenomegaly, the long-term transitional trend of the splenic size and PV diameter may increase along with children's growth. The PV flow reached a stable status 6 to 9 months after LDLT and remained so until 10 years after LDLT., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Object: There is mounting clinical evidence that an increase in obesity is linked to an increase in cancer incidence and mortality. Although studies have shown a link between obesity and colon cancer, the particular mechanism of the interaction between obesity and colon cancer in females remains unknown. The goal of this work is to use bioinformatics to elucidate the genetic link between obesity and colon cancer in females and to investigate probable molecular mechanisms., Methods: GSE44076 and GSE199063 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. In the two microarray datasets and healthy controls, the online tool GEO2R was utilized to investigate the differential genes between obesity and colon cancer. The differential genes (DEGs) identified in the two investigations were combined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were performed on the DEGs. The STRING database and Cytoscape software were then used to build protein-protein interaction (PPI) networks to discover hub genes. NetworkAnalyst was also used to build networks of target microRNAs (miRNAs) and hub genes, as well as networks of transcriptions., Results: Between the two datasets, 146 DEGs were shared. The DEGs are primarily enriched in inflammatory and immune-related pathways, according to GO analysis and KEGG. 14 hub genes were identified via PPI building using the Cytoscape software's MCODE and CytoNCA plug-ins: TYROBP, CD44, BGN, FCGR3A, CD53, CXCR4, FN1, SPP1, IGF1, CCND1, MMP9, IL2RG, IL6 and CTGF. Key transcription factors for these hub genes include WRNIP1, ATF1, CBFB, and NR2F6. Key miRNAs for these hub genes include hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-164a-5p and hsa-mir-9-5p., Conclusion: Our research provides evidence that changed genes are shared by female patients with colon cancer and obesity. Through pathways connected to inflammation and the immune system, these genes play significant roles in the emergence of both diseases. We created a network between hub genes and miRNAs that target transcription factors, which may offer suggestions for future research in this area., 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 © 2023 Zhang, Zhang, Fang, Li, Shu, Gong, Luo and Tian.)

An optimal wound-healing hydrogel requires effective antibacterial properties and a favorable cell adhesion and proliferation environment. Although Bombyx mori silk fibroin (SF) possesses inherent wound-healing properties, it lacks these essential qualities. This study aimed to fabricate a novel photo-polymerizable hydrogel by utilizing SF's wound-healing efficiency and the epsilon-poly-L-lysine (EPL) antimicrobial activity. The SF was modified with three different concentrations of glycidyl methacrylate (GMA) to obtain SF-GMA(L), SF-GMA(M), and SF-GMA(H). A methacrylated EPL (EPL-GMA) was also produced. Then, SF-GMA was mixed with EPL-GMA to produce photo-crosslinkable SF-GMA-EPL hydrogels. The SF-GMA(L)-EPL, SF-GMA(M)-EPL, and SF-GMA(H)-EPL hydrogels, fabricated with 20% EPL-GMA, demonstrated maximum antimicrobial activity and mammalian cell adhesion ability. The hydroxyl radical (•OH) scavenging efficiency of the hydrogels was tested and shown to be between 69% and 74%. These hydrogels also exhibited 60% efficiency in removing bacterial lipopolysaccharides. The water absorption ability of the hydrogels was consistent with the size of their internal pores. The hydrogels exhibited a slow degradation fashion, and their degradation products appeared cytocompatible. Finally, the elastomeric properties of the hydrogels were determined, and a storage modulus (G') of 300-600 Pa was demonstrated. In conclusion, the hydrogels created in this study possess excellent biological and physical properties to support wound healing., (© 2023 IOP Publishing Ltd.)

Laser powder bed fusion (LPBF) provides a rapid and versatile approach for producing parts with complex geometries. However, many parts with intricate geometries have overhang structures, which are not easily fabricated by using LPBF and are often downgraded by staircase effects, warpage, cracks, and dross formation. Thus, the present study proposes a combined numerical and experimental approach for determining the optimal settings of the laser power and scanning speed that minimize the surface roughness and maximize the density of Inconel 718 LPBF overhang structures. In the proposed approach, the heat transfer simulations are employed to determine the melt pool depth, the melt pool length, and the solid cooling rate within the feasible input space of laser power and scanning speed combinations. Notably, the simulations take account of both the difference in the material properties of the solid and powder materials, respectively, and the variation of the laser absorptivity in the depth direction of the powder layer. The simulation results are then used to train artificial neural networks for predicting the melt pool depth for 3600 combinations of the laser power and scanning speed within the input space. The resulting processing maps are screened in accordance with three quality criteria (namely the melt pool depth, the melt pool length, and the solid cooling rate) to determine the optimal processing region, which improves the surface roughness. The feasibility of the proposed approach is demonstrated by fabricating 10 × 10 and 20 × 20 mm 2 horizontal overhang structures using parameter settings chosen from the optimal processing map. It shows that the optimal processing conditions result in a low surface roughness and a maximum density of 99.78%., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

Substance use disorders (SUD) can lead to serious health problems, and there is a great interest in developing new treatment methods to alleviate the impact of substance abuse. In recent years, the ketogenic diet (KD) has shown therapeutic benefits as a dietary therapy in a variety of neurological disorders. Recent studies suggest that KD can compensate for the glucose metabolism disorders caused by alcohol use disorder by increasing ketone metabolism, thereby reducing withdrawal symptoms and indicating the therapeutic potential of KD in SUD. Additionally, SUD often accompanies increased sugar intake, involving neural circuits and altered neuroplasticity similar to substance addiction, which may induce cross-sensitization and increased use of other abused substances. Reducing carbohydrate intake through KD may have a positive effect on this. Finally, SUD is often associated with mitochondrial damage, oxidative stress, inflammation, glia dysfunction, and gut microbial disorders, while KD may potentially reverse these abnormalities and serve a therapeutic role. Although there is much indirect evidence that KD has a positive effect on SUD, the small number of relevant studies and the fact that KD leads to side effects such as metabolic abnormalities, increased risk of malnutrition and gastrointestinal symptoms have led to the limitation of KD in the treatment of SUD. Here, we described the organismal disorders caused by SUD and the possible positive effects of KD, aiming to provide potential therapeutic directions for SUD., 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 © 2023 Kong, Sun, Yang, Li, Bi, Zhang, Wang, Luo, Zhu and Xu.)

Wet air oxidation (WAO) is a clean and eco-friendly technology for dyes removal, but the high operating temperature and pressure limit its practical application. In the present work, an electric field-promoting (EF-promoting) catalytic WAO process is developed to degrade dyes under room condition. The oxidation kinetics of four different types of dyes and their degradation pathways are studied. A kinetic model is constructed by including the exogenous electric field into the Langmuir-Hinshelwood-Hougen-Watson (LHHW) mechanism framework, and quantitative structure-activity relationship (QSAR) analysis is conducted to correlate the kinetic parameters to the physicochemical properties of the dyes. A negative linear relationship is found between the adsorption equilibrium constants of the dyes and their first ionization energies, and their surface reaction rate constants are positively linearly associated to E sum (E LUMO  + E HOMO ). The degradation pathways of the different dyes are proposed according to the degradation intermediates and the activities of the atoms within the dye molecules. The heteroatoms N and S, and the atom C connecting the aromatic rings are identified as the susceptible sites upon the electrophilic attack of O 2 . Bond cleavage at these sites gives rise to aromatic fragments which are eventually mineralized via carboxyl acids. The results of this work is helpful for guiding the design and operation of the EF-promoting catalytic WAO process into the treatment of various dye wastewaters., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Min Sun reports financial support was provided by National Natural Science Foundation of China. Min Sun reports financial support was provided by Anhui Provincial Natural Science Foundation., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810)., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Achieving high mobility and reliability in atomic layer deposition (ALD)-based IGZO thin-film transistors (TFTs) with an amorphous phase is vital for practical applications in relevant fields. Here, we suggest a method to effectively increase stability while maintaining high mobility by employing the selective application of nitrous oxide plasma reactant during plasma-enhanced ALD (PEALD) at 200 °C process temperature. The nitrogen-doping mechanism is highly dependent on the intrinsic carbon impurities or nature of each cation, as demonstrated by a combination of theoretical and experimental research. The Ga 2 O 3 subgap states are especially dependent on plasma reactants. Based on these insights, we can obtain high-performance indium-rich PEALD-IGZO TFTs (threshold voltage: -0.47 V; field-effect mobility: 106.5 cm 2 /(V s); subthreshold swing: 113.5 mV/decade; hysteresis: 0.05 V). In addition, the device shows minimal threshold voltage shifts of +0.45 and -0.10 V under harsh positive/negative bias temperature stress environments (field stress: ±2 MV/cm; temperature stress: 95 °C) after 10000 s.

Objective: In this study, we aimed to investigate Bregs, their regulatory effects on Th17/Treg cell balance, and the release of downstream inflammatory factors in a mouse model of low-density lipoprotein receptor (LDLr) -/-  + Pristane., Methods: After the establishment of the mouse model of systemic lupus erythematosus (SLE) complicated with atherosclerosis (AS), 8-week-old LDLr -/-  + Pristane mice (n = 10) were included in the SLE + AS group. Furthermore, 8-week-old MRL/lpr and C57 mice were used as the SLE and normal control groups, respectively (n = 10 per group). After feeding the mice a high-fat diet for 14 weeks, peripheral blood and spleen of mice were collected, and Bregs, Th17, and Treg cells and related inflammatory factors were detected by flow cytometry, enzyme-linked immunosorbent assay, and reverse-transcription polymerase chain reaction., Results: The number of Bregs and Tregs in spleen lymphocytes of SLE + AS mice significantly decreased compared with the C57 group (p < .05), whereas the number of Th17 cells significantly increased (p = .000). Furthermore, the proportion of Bregs showed a negative correlation with the Th17/Treg ratio (p = .03). Mice in the SLE + AS group showed higher serum interleukin (IL)-10, IL-17, and tumor necrosis factor-α levels than those in the SLE and C57 groups (p < .05). Furthermore, IL-35 and transforming growth factor (TGF)-β expression was reduced in the SLE + AS group compared with the C57 group (p < .05)., Conclusions: The proportion of Breg decreases was negatively associated with increased Th17/Treg which was increased in SLE + AS mice, indicating that Bregs may regulate Th17/Treg cell homeostasis and cytokine release via IL-35 and TGF-β production., (© 2023 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

The bloodsucking fly, Stomoxys calcitrans (Diptera: Muscidae), is a cosmopolitan pest that transmits potential pathogens mechanically. We conduct phylogeographic analyses of S. calcitrans to resolve its global population genetic structure for establishing baseline of molecular studies. Results from mitochondrial gene suggested that the major divergence of S. calcitrans predominantly occurred 0.32-0.47 million years ago (Mya) and the subsequent diversifications took place during 0.13-0.27 Mya. The Ethiopian region was deduced as the most likely origin of S. calcitrans and the Nearctic lineages were considered to have originated from Oriental or Palaearctic regions. Our results further revealed that each biogeographic region of S. calcitrans likely maintains its genetic specialty, and yet, those non-monophyletic relationships were possibly caused by ancestral retention, dispersal with mammals, long-distance migration, and the international livestock industries. Moreover, the three highly diverged Ethiopian lineages may be putative cryptic species that require clarification of their veterinary importance. Unravelling the genetic structure of stable fly and preventing gene flow among biogeographic regions through anthropogenic activities are thus pivotal in livestock industry administration, particularly genetic exchange among differentiated lineages that might lead to the consequence of ecological trait alterations., (© 2023 The Royal Entomological Society.)

Reinforcement learning agents that have not been seen during training must be robust in test environments. However, the generalization problem is challenging to solve in reinforcement learning using high-dimensional images as the input. The addition of a self-supervised learning framework with data augmentation in the reinforcement learning architecture can promote generalization to a certain extent. However, excessively large changes in the input images may disturb reinforcement learning. Therefore, we propose a contrastive learning method that can help manage the trade-off relationship between the performance of reinforcement learning and auxiliary tasks against the data augmentation strength. In this framework, strong augmentation does not disturb reinforcement learning and instead maximizes the auxiliary effect for generalization. Results of experiments on the DeepMind Control suite demonstrate that the proposed method effectively uses strong data augmentation and achieves a higher generalization than the existing methods.

Post-arthroplasty periprosthetic joint infection (PJI) is a serious ailment that can be difficult to diagnose. Herein, we developed a novel integrated microfluidic system (IMS) capable of detecting two common PJI biomarkers, alpha defensin human neutrophil peptide 1 (HNP-1) and C-reactive protein (CRP), from synovial fluid (SF). A magnetic bead-based one-aptamer-one-antibody assay was carried out automatically within 45 min on a single chip for simultaneous detection of both biomarkers at concentration ranges of 0.01-50 (HNP-1) and 1-100 (CRP) mg/L. It is the first report for utilizing these two biomarkers as targets to establish the new one-aptamer-one-antibody assay to detect PJI on-chip, and the aptamers demonstrated high specificity to their SF targets. As 20 clinical samples were correctly diagnosed with our IMS (verified by a common gold standard kit), it could serve as a promising tool for PJI diagnostics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to pose threats to public health. The clinical manifestations of lung pathology in COVID-19 patients include sustained inflammation and pulmonary fibrosis. The macrocyclic diterpenoid ovatodiolide (OVA) has been reported to have anti-inflammatory, anti-cancer, anti-allergic, and analgesic activities. Here, we investigated the pharmacological mechanism of OVA in suppressing SARS-CoV-2 infection and pulmonary fibrosis in vitro and in vivo. Our results revealed that OVA was an effective SARS-CoV-2 3CLpro inhibitor and showed remarkable inhibitory activity against SARS-CoV-2 infection. On the other hand, OVA ameliorated pulmonary fibrosis in bleomycin (BLM)-induced mice, reducing inflammatory cell infiltration and collagen deposition in the lung. OVA decreased the levels of pulmonary hydroxyproline and myeloperoxidase, as well as lung and serum TNF-ɑ, IL-1β, IL-6, and TGF-β in BLM-induced pulmonary fibrotic mice. Meanwhile, OVA reduced the migration and fibroblast-to-myofibroblast conversion of TGF-β1-induced fibrotic human lung fibroblasts. Consistently, OVA downregulated TGF-β/TβRs signaling. In computational analysis, OVA resembles the chemical structures of the kinase inhibitors TβRI and TβRII and was shown to interact with the key pharmacophores and putative ATP-binding domains of TβRI and TβRII, showing the potential of OVA as an inhibitor of TβRI and TβRII kinase. In conclusion, the dual function of OVA highlights its potential for not only fighting SARS-CoV-2 infection but also managing injury-induced pulmonary fibrosis., Competing Interests: Conflict of interest statement The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Masson SAS.)

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome with multiple underlying mechanisms and comorbidities that leads to a variety of clinical phenotypes. The identification and characterization of these phenotypes are essential for better understanding the precise pathophysiology of HFpEF, identifying appropriate treatment strategies, and improving patient outcomes. Despite accumulating data showing the potentiality of artificial intelligence (AI)-based phenotyping using clinical, biomarker, and imaging information from multiple dimensions in HFpEF management, contemporary guidelines and consensus do not incorporate these in daily practice. In the future, further studies are required to authenticate and substantiate these findings in order to establish a more standardized approach for clinical implementation.

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: Whether insulin resistance underlies deep venous thrombosis (DVT) development in patients with severe traumatic brain injury (TBI) is unclear. In this study, the association between plasma insulin levels and DVT was analyzed in patients with severe TBI., Methods: A prospective observational study of 73 patients measured insulin, glucose, glucagon-like peptide 1 (GLP-1), inflammatory factors, and hematological profiles within four preset times during the first 14 days after TBI. Ultrasonic surveillance of DVT was tracked. Two-way analysis of variance was used to determine the factors that discriminated between patients with and without DVT or with and without insulin therapy. Partial correlations of insulin level with all the variables were conducted separately in patients with DVT or patients without DVT. Factors associated with DVT were analyzed by multivariable logistic regression. Neurological outcomes 6 months after TBI were assessed., Results: Among patients with a mean (± standard deviation) age of 53 (± 16 years), DVT developed in 20 patients (27%) on median 10.4 days (range 4-22), with higher Acute Physiology and Chronic Health Evaluation II scores but similar Sequential Organ Failure Assessment scores and TBI severity. Patients with DVT were more likely to receive insulin therapy than patients without DVT (60% vs. 28%; P = 0.012); hence, they had higher 14-day insulin levels. However, insulin levels were comparable between patients with DVT and patients without DVT in the subgroups of patients with insulin therapy (n = 27) and patients without insulin therapy (n = 46). The platelet profile significantly discriminated between patients with and without DVT. Surprisingly, none of the coagulation profiles, blood cell counts, or inflammatory mediators differed between the two groups. Patients with insulin therapy had significantly higher insulin (P = 0.006), glucose (P < 0.001), and GLP-1 (P = 0.01) levels and were more likely to develop DVT (60% vs. 15%; P < 0.001) along with concomitant platelet depletion. Insulin levels correlated with glucose, GLP-1 levels, and platelet count exclusively in patients without DVT. Conversely, in patients with DVT, insulin correlated negatively with GLP-1 levels (P = 0.016). Age (P = 0.01) and elevated insulin levels at days 4-7 (P = 0.04) were independently associated with DVT. Patients with insulin therapy also showed worse Glasgow Outcome Scale scores (P = 0.001)., Conclusions: Elevated insulin levels in the first 14 days after TBI may indicate insulin resistance, which is associated with platelet hyperactivity, and thus increasing the risk of DVT., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Mitochondrial Hsp60 (mtHsp60) plays a crucial role in maintaining the proper folding of proteins in the mitochondria. mtHsp60 self-assembles into a ring-shaped heptamer, which can further form a double-ring tetradecamer in the presence of ATP and mtHsp10. However, mtHsp60 tends to dissociate in vitro, unlike its prokaryotic homologue, GroEL. The molecular structure of dissociated mtHsp60 and the mechanism behind its dissociation remain unclear. In this study, we demonstrated that Epinephelus coioides mtHsp60 (EcHsp60) can form a dimeric structure with inactive ATPase activity. The crystal structure of this dimer reveals symmetrical subunit interactions and a rearranged equatorial domain. The α4 helix of each subunit extends and interacts with its adjacent subunit, leading to the disruption of the ATP-binding pocket. Furthermore, an RLK motif in the apical domain contributes to stabilizing the dimeric complex. These structural and biochemical findings provide new insights into the conformational transitions and functional regulation of this ancient chaperonin., (© 2023 Lai et al.)

Objective: We aimed to explore the applicability and safety of micro-percutaneous nephrolithotomy (micro-perc) in the treatment of children with kidney stones in the Galdakao-modified supine Valdivia (GMSV) position under the guidance of whole-course ultrasound., Materials and Methods: Patients were aged < 18 years in the GMSV position who underwent micro-perc for kidney stones under ultrasound guidance between August 2020 and May 2022 at our institution were reviewed retrospectively., Results: A total of 23 patients, 15 males and 8 females, received micro-perc. The average stone size was 1.6 cm (range 1.1-2.0 cm). Among them, 12 patients had left kidney stones, 10 patients had right kidney stones, and 1 patient had bilateral kidney stones. The mean operative time was 55.3 min (range 35-86 min). The mean hospital stay was 2.9 days (range 2-4 days). The mean hemoglobin decrease was 1.7 g/L (range 0.9-3.2 g/L). A total of 17 patients had complete stone clearance at 48 h postoperatively. A total of 22 patients had complete stone clearance at 2 weeks postoperatively., Conclusion: Our results demonstrate that micro-perc under ultrasound guidance is a safe and effective method for the treatment of children with kidney stones in the GMSV position. Further research is warranted to confirm these results., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)