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Abstract Hyperactive Ras signalling is found in most cancers. Ras proteins are only active in membrane nanoclusters, which are therefore potential drug targets. We previously showed that the nanocluster scaffold galectin-1 (Gal1) enhances H-Ras nanoclustering via direct interaction with the Ras binding domain (RBD) of Raf. Here, we establish that the B-Raf preference of Gal1 emerges from the divergence of the Raf RBDs at their proposed Gal1-binding interface. We then identify the L5UR peptide, which disrupts this interaction by binding with low micromolar affinity to the B- and C-Raf-RBDs. Its 23-mer core fragment is sufficient to interfere with H-Ras nanoclustering, modulate Ras-signalling and moderately reduce cell viability. These latter two phenotypic effects may also emerge from the ability of L5UR to broadly engage with several RBD- and RA-domain containing Ras interactors. The L5UR-peptide core fragment is a starting point for the development of more specific reagents against Ras-nanoclustering and -interactors.

Abstract Background The weight-adjusted waist index (WWI) is a recently developed obesity metric, and the aim of this study was to investigate the relationship between physical activity (PA) and WWI and the homeostasis model assessment of insulin resistance (HOMA-IR) in adolescents, as well as the joint association of HOMA-IR. Methods This study was based on the National Health and Nutrition Survey conducted between 2013 and 2016 and included 1024 adolescents whose median age was 15.4. Multivariate linear regression was used to examine the associations between HOMA-IR and PA and WWI. Using generalized additive models, a potential nonlinear link between WWI and HOMA-IR was evaluated. Subgroup analysis was also carried out. Results The fully adjusted model revealed a positive association (β: 0.48, 95% CI: 0.43, 0.53) between the WWI and HOMA-IR. The HOMA-IR was lower in physically active (β: -0.16, 95% CI: -0.26, -0.05) participants versus inactive participants. Participants who had higher WWI and were not physically active (β: 0.69; 95% CI: 0.56, 0.82) had the highest levels of HOMA-IR compared to participants who had lower WWI and were physically active. Subgroup analysis revealed that these correlations were similar in males and females. Conclusion Our results demonstrated that higher WWI and PA were associated with a lower HOMA-IR and that WWI and PA had a combined association with HOMA-IR. The findings of this study are informative for the preventing insulin resistance in adolescents.

Objective Management of extensive acetabular bone defects in total hip arthroplasty (THA) remains challenging. This study aims to investigate the feasibility and preliminary outcomes of 3D‐printed personalized porous acetabular components for the reconstruction of acetabular defects in primary THA. Methods This retrospective study involved seven patients who received 3D‐printed acetabular components in primary THA between July 2018 and March 2021. Preoperatively, acetabular bone defects were evaluated by referencing the Paprosky classification. There were two "Paprosky type IIIA" defects and five "Paprosky type IIIB" defects. The acetabular components were custom‐made for each patient to reconstruct the extensive acetabular defects. The hip function was assessed according to the Harris hip score (HHS). Clinical and radiographic outcomes were assessed. Results The average follow‐up period was 40 months, ranging from 26 to 57 months. There were no patients lost to follow‐up. The HHS improved from 44 (range: 33–53) before the operation to 88 (range: 79–93) at the final follow‐up. Postoperative X‐rays showed that the 3D‐printed personalized components were properly fitted with the acetabulum. The average center of rotation (COR) discrepancy was 2.3 mm horizontally and 2.1 mm vertically, respectively. Tomosynthesis‐Shimadzu metal artifact reduction technology images showed that the implant was in close contact with the host bone. Moreover, no complications were observed during the follow‐up period, including loosening, dislocation, or component protrusion. Conclusion The implantation of 3D‐printed personalized acetabular components showed accurate reconstruction, stable mechanical support, and favorable function at short‐term follow‐up. This may be a viable alternative method for reconstructing extensive acetabular defects in THA.

This is an article in the field of mineral materials. The utilization of desulfurized gypsum (FGD) to prepare more widely used hemihydrate gypsum plays a very important role in the resource utilization of industrial by-product gypsum. It can not only avoid the large-scale exploitation of natural gypsum, but also realize the resource utilization of desulfurized gypsum. In the process of converting FGD gypsum into hemihydrate gypsum, appropriate concentration of additive and sodium chloride were used as the reaction solution, and the process was heated and stirred under normal pressure. The effects of sodium chloride concentration, additive concentration, solid-liquid ratio, rotation speed and reaction temperature on the phase conversion time and crystal size of dihydrate to hemihydrate gypsum were studied. The increase of additive and sodium chloride concentration not only sped up the phase conversion process but also had a certain inhibitory effect on the average length and average aspect ratio of hemihydrate gypsum crystals. Higher or lower rotation speed hindered the nucleation and growth of hemihydrate gypsum crystals and affected the collision frequency of Ca2+ and SO42- in the NaCl added solution, thus delaying the formation of hemihydrate gypsum. Decreasing the solid-liquid ratio and increasing the temperature had a certain promoting effect on the phase conversion process. At a lower temperature, due to the insufficient driving force of the phase conversion process, it was difficult to transform FGD gypsum into hemihydrate gypsum. The optimal process conditions for preparing hemihydrate gypsum from FGD gypsum were determined as follows: sodium chloride concentration 10%, additive concentration 10%, solid-liquid ratio 1∶5, rotating speed 300 r/min, reaction temperature 100 ℃. Under the best process conditions, the reaction could be completed in 60 min. The average length of the prepared hemihydrate gypsum crystals was as high as 127 μm, and the average aspect ratio was as high as 19. At the same time, the relationship between the activity of water molecules in the solution, the degree of supersaturation and the reaction temperature was studied, and it was determined that the phase conversion process was determined by the temperature and the degree of supersaturation.

Abstract This article addresses the phenomenon of Netspeak reductions with special reference to Mandarin computer-mediated communication. A tentative classification of Chinese Netspeak reductions is first provided, namely, two-, three-, or four-character reductions occurring at both the lexical and the syntactic levels and other atypical reductions. It is then proposed that Zipf’s Principle of Least Effort, which usually works at the lexical level, can work as well at the utterance level and can account for the increasing number of Netspeak reductions in daily communication, that is, the frequency of using Netspeak reduction determines its vitality and distribution.

Abstract Background The epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBECs) is essential for airway remodeling during asthma. Wnt5a has been implicated in various lung diseases, while its role in the EMT of HBECs during asthma is yet to be determined. This study sought to define whether Wnt5a initiated EMT, leading to airway remodeling through the induction of autophagy in HBECs. Methods Microarray analysis was used to investigate the expression change of WNT5A in asthma patients. In parallel, EMT models were induced using 16HBE cells by exposing them to house dust mites (HDM) or interleukin-4 (IL-4), and then the expression of Wnt5a was observed. Using in vitro gain- and loss-of-function approaches via Wnt5a mimic peptide FOXY5 and Wnt5a inhibitor BOX5, the alterations in the expression of the epithelial marker E-cadherin and the mesenchymal marker protein were observed. Mechanistically, the Ca2+/CaMKII signaling pathway and autophagy were evaluated. An autophagy inhibitor 3-MA was used to examine Wnt5a in the regulation of autophagy during EMT. Furthermore, we used a CaMKII inhibitor KN-93 to determine whether Wnt5a induced autophagy overactivation and EMT via the Ca2+/CaMKII signaling pathway. Results Asthma patients exhibited a significant increase in the gene expression of WNT5A compared to the healthy control. Upon HDM and IL-4 treatments, we observed that Wnt5a gene and protein expression levels were significantly increased in 16HBE cells. Interestingly, Wnt5a mimic peptide FOXY5 significantly inhibited E-cadherin and upregulated α-SMA, Collagen I, and autophagy marker proteins (Beclin1 and LC3-II). Rhodamine-phalloidin staining showed that FOXY5 resulted in a rearrangement of the cytoskeleton and an increase in the quantity of stress fibers in 16HBE cells. Importantly, blocking Wnt5a with BOX5 significantly inhibited autophagy and EMT induced by IL-4 in 16HBE cells. Mechanistically, autophagy inhibitor 3-MA and CaMKII inhibitor KN-93 reduced the EMT of 16HBE cells caused by FOXY5, as well as the increase in stress fibers, cell adhesion, and autophagy. Conclusion This study illustrates a new link in the Wnt5a-Ca2+/CaMKII-autophagy axis to triggering airway remodeling. Our findings may provide novel strategies for the treatment of EMT-related diseases.

Abstract Background Glyphosate is a commonly used herbicide worldwide and is purportedly associated with multiple health effects. Research assessing the association of glyphosate concentrations with glycosylated hemoglobin (HbA1c) levels and the prevalence of diabetes is scarce. We sought to evaluate the association between urinary glyphosate levels and HbA1c levels and the prevalence of diabetes. Methods A total of 2,745 adults in the National Health and Nutrition Examination Survey from 2013 to 2016 were included in this study. Generalized linear models (GLM) were applied to evaluate the associations of glyphosate concentrations with HbA1c levels and the prevalence of diabetes. The dose–response relationship was examined using restricted cubic splines (RCS). Results Significantly positive correlations of urinary glyphosate concentrations with HbA1c levels (percentage change: 1.45; 95% CI: 0.95, 1.96; P

Abstract The importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC.

Abstract Background To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia. Methods We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits. Results The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P

Abstract Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial–mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity. Graphical Abstract

Abstract Abscisic acid (ABA) plays a crucial role in promoting plant stress resistance and seed dormancy. However, how ABA regulates rice quality remains unclear. This study identifies a key transcription factor SLR1-like2 (SLRL2), which mediates the ABA-regulated amylose content (AC) of rice. Mechanistically, SLRL2 interacts with NF-YB1 to co-regulate Wx, a determinant of AC and rice quality. In contrast to SLR1, SLRL2 is ABA inducible but insensitive to GA. In addition, SLRL2 exhibits DNA-binding activity and directly regulates the expression of Wx, bHLH144 and MFT2. SLRL2 competes with NF-YC12 for interaction with NF-YB1. NF-YB1 also directly represses SLRL2 transcription. Genetic validation supports that SLRL2 functions downstream of NF-YB1 and bHLH144 in regulating rice AC. Thus, an NF-YB1-SLRL2-bHLH144 regulatory module is successfully revealed. Furthermore, SLRL2 regulates rice dormancy by modulating the expression of MFT2. In conclusion, this study revealed an ABA-responsive regulatory cascade that functions in both rice quality and seed dormancy.

Cornus hongkongensis Hemsl. 1888, native to Hong Kong, belongs to the subgenus Syncarpea within the Cornus genus of the Cornaceae family. The complete chloroplast genome of C. hongkongensis spans 156,954 bp, comprising four subregions: a large single-copy region (86,290 bp), a small single-copy region (18,394 bp), and a pair of inverted repeats (26,135 bp). Within the chloroplast genome of C. hongkongensis, we identified 113 unique genes, including 80 protein-encoding genes, four ribosomal RNA (rRNA) genes, and 30 transfer RNA (tRNA) genes. Phylogenetic analysis based on the complete chloroplast genome of 30 related taxa of the Cornus genus indicates that C. hongkongensis has not formed a monophyletic lineage. Analyses of sequence divergence found three intergenic regions including rps19-rpl22, ccsA-ndhD, and atpH-atpI, exhibiting a high degree of variations. The first chloroplast genome of C. hongkongensis was reported in this work contributes to the enrichment of genomic data for the genus Cornus.

Background: The cartilage stem/progenitor cells (CSPC) play a critical role in maintaining cartilage homeostasis. However, the effects of phenotypic fluctuations of CSPC on cartilage degeneration and the role of CSPC in the pathogenesis of OA is largely unknown. Methods: The cartilage samples of 3 non-OA and 10 OA patients were collected. Human CSPC (hCSPC) derived from these patients were isolated, identified, and evaluated for cellular functions. Additionally, chondrocytes derived from OA patients were isolated. The effect of Yes-associated protein (YAP) expression on hCSPC was investigated in vitro. The OA rat model was established by Hulth's method. Lentivirus-mediated YAP (Lv-YAP) or lentivirus-mediated YAP RNAi (Lv-YAP-RNAi) was injected intra-articularly to modulate YAP expression in rat joints. In addition, allogeneic rat CSPC (rCSPC) overexpressing or silencing YAP were transplanted by intra-articularly injection. We also evaluated the functions of rCSPC and the OA-related cartilage phenotype in the rat model. Finally, the transcriptome of OA rCSPC overexpressing YAP was examined to explore the potential downstream targets of YAP in rCSPC. Results: hCSPC derived from OA patients exhibited differential chondrogenesis capacity. Among them, a subset of hCSPC showed pronounced dysfunction, including impaired chondrogenic differentiation, inhibition of proliferation and migration, and downregulation of lubricin. Additionally, YAP was lowly expressed in quiescent non-OA hCSPC, upregulated in activated OA hCSPC, but significantly downregulated in dysfunctional OA hCSPC. Notably, the overexpression of YAP in OA hCSPC improved the proliferation, lubricin production, cell migration, and senescence, while silencing YAP had the opposite effect. In vivo, upregulation of YAP in the joint delayed OA progression and improved the cartilage regeneration capacity of rCSPC. Using transcriptomic analysis, we found that YAP may regulate rCSPC function by upregulating Baculoviral IAP repeat-containing 2 (BIRC2). Importantly, the knockdown of BIRC2 partly blocked the regulation of YAP on the CSPC function. Conclusion: Dysfunction of CSPC compromises the intrinsic repair capacity of cartilage and impairs cartilage homeostasis in OA. Notably, the transcriptional co-activator YAP plays a critical role in maintaining CSPC function through potential target gene BIRC2. The Translational Potential of this Article: In this study, we observed targeting the YAP-BIRC2 axis improved the CSPC function and restored the cartilage homeostasis in OA. This study provides a potential stem cell-modifying OA therapy.

Irreducible anteromedial radial head dislocation (IARHD) caused by transposed biceps tendon is rare. Delayed diagnosis and surgical failure often occur. A 46-year-old fisherman presented with 10 days history of painful swelling and restricted movement of his right elbow due to strangulation injury by a fishing boat cable. On examination, the images of the right elbow reveals in a ''semi-extended and pronated'' elastic fixation position. Radiography and 3-dimensional reconstruction CT reveals an isolated anteromedial radial head dislocation with extreme protonation of the radius and the bicipital tuberosity towards the posterior aspect of the elbow joint, and MRI shows biceps tendon wrapping around the radial neck, similar to umbilical cord wrapping seen in newborns. The Henry approach was applied for the first time to reduce the biceps tendon. The patient achieved a good functional recovery at 26 months, which represents the first reported case of IARHD without fracture caused by biceps tendon in an adult. In treatment of IARHD, attention should be paid to the phenomenon of biceps tendon transposition. Careful clinical examination, comprehensive imaging modalities, and appropriate surgical approach are the keys to successful management.

Abstract Background Customized 3D-printed pelvic implants with a porous structure have revolutionized periacetabular pelvic defect reconstruction after tumor resection, offering improved osteointegration, long-term stability, and anatomical fit. However, the lack of an established classification system hampers implementation and progress. Methods We formulated a novel classification system based on pelvic defect morphology and 3D-printed hemipelvis endoprostheses. It integrates surgical approach, osteotomy guide plate and prosthesis design, postoperative rehabilitation plans, and perioperative processes. Results Retrospectively analyzing 60 patients (31 males, 29 females), we classified them into Type A (15 patients: Aa = 6, Ab = 9), Type B (27 patients: Ba = 15, Bb = 12), Type C (17 patients). All underwent customized osteotomy guide plate-assisted tumor resection and 3D-printed hemipelvic endoprosthesis reconstruction. Follow-up duration was median 36.5 ± 15.0 months (range, 6 to 74 months). The mean operating time was 430.0 ± 106.7 min, intraoperative blood loss 2018.3 ± 1305.6 ml, transfusion volume 2510.0 ± 1778.1 ml. Complications occurred in 13 patients (21.7%), including poor wound healing (10.0%), deep prosthesis infection (6.7%), hip dislocation (3.3%), screw fracture (1.7%), and interface loosening (1.7%). VAS score improved from 5.5 ± 1.4 to 1.7 ± 1.3, MSTS-93 score from 14.8 ± 2.5 to 23.0 ± 5.6. Implant osseointegration success rate was 98.5% (128/130), with one Type Ba patient experiencing distal prosthesis loosening. Conclusion The West China classification may supplement the Enneking and Dunham classification, enhancing interdisciplinary communication and surgical outcomes. However, further validation and wider adoption are required to confirm clinical effectiveness.

Abstract Background Talar malignant tumor is extremely rare. Currently, there are several alternative management options for talus malignant tumor including below-knee amputation, tibio-calcaneal arthrodesis, and homogenous bone transplant while their shortcomings limited the clinical application. Three-dimensional (3D) printed total talus prosthesis in talus lesion was reported as a useful method to reconstruct talus, however, most researches are case reports and its clinical effect remains unclear. Therefore, the current study was to explore the application of 3D printed custom-made modular prosthesis in talus malignant tumor. Methods We retrospectively analyzed the patients who received the 3D printed custom-made modular prosthesis treatment due to talus malignant tumor in our hospital from February 2016 to December 2021. The patient's clinical data such as oncology outcome, operation time, and volume of blood loss were recorded. The limb function was evaluated with the Musculoskeletal Tumor Society 93 (MSTS-93) score, The American Orthopedic Foot and Ankle Society (AOFAS) score; the ankle joint ranges of motion as well as the leg length discrepancy were evaluated. Plain radiography and Tomosynthesis-Shimadzu Metal Artefact Reduction Technology (T-SMART) were used to evaluate the position of prosthesis and the osseointegration. Postoperative complications were recorded. Results The average patients’ age and the follow-up period were respectively 31.5 ± 13.1 years; and 54.8 months (range 26–72). The medium operation time was 2.4 ± 0.5 h; the intraoperative blood loss was 131.7 ± 121.4 ml. The mean MSTS-93 and AOFAS score was 26.8 and 88.5 respectively. The average plantar flexion, dorsiflexion, varus, and valgus were 32.5, 9.2, 10.8, and 5.8 degree respectively. One patient had delayed postoperative wound healing. There was no leg length discrepancy observed in any patient and good osseointegration was observed on the interface between the bone and talus prosthesis in all subjects. Conclusion The modular structure of the prosthesis developed in this study seems to be convenient for prosthesis implantation and screws distribution. And the combination of solid and porous structure improves the initial stability and promotes bone integration. Therefore, 3D printed custom-made modular talus prosthesis could be an alternative option for talus reconstruction in talus malignant tumor patients.

Influenza A/H9 viruses circulate worldwide in wild and domestic avian species, continuing to evolve and posing a zoonotic risk. A substantial increase in human infections with A/H9N2 subtype avian influenza viruses (AIVs) and the emergence of novel reassortants carrying A/H9N2-origin internal genes has occurred in recent years. Different names have been used to describe the circulating and emerging A/H9 lineages. To address this issue, an international group of experts from animal and public health laboratories, endorsed by the WOAH/FAO Network of Expertise on Animal Influenza, has created a practical lineage classification and nomenclature system based on the analysis of 10,638 hemagglutinin sequences from A/H9 AIVs sampled worldwide. This system incorporates phylogenetic relationships and epidemiologic characteristics designed to trace emerging and circulating lineages and clades. To aid in lineage and clade assignment, an online tool has been created. This proposed classification enables rapid comprehension of the global spread and evolution of A/H9 AIVs.

Haptic is the modality that complements traditional multimedia, i.e., audiovisual, to evolve the next wave of innovation at which the Internet data stream can be exchanged to enable remote skills and control applications. This will require ultra-low latency and ultra-high reliability to evolve the mobile experience into the era of Digital Twin and Tactile Internet. While the 5th generation of mobile networks is not yet widely deployed, Long-Term Evolution (LTE-A) latency remains much higher than the 1 ms requirement for the Tactile Internet and therefore the Digital Twin. This work investigates an interesting solution based on the incorporation of Software-defined networking (SDN) and Multi-access Mobile Edge Computing (MEC) technologies in an LTE-A network, to deliver future multimedia applications over the Tactile Internet while overcoming the QoS challenges. Several network scenarios were designed and simulated using Riverbed modeler and the performance was evaluated using several time-related Key Performance Indicators (KPIs) such as throughput, End-2-End (E2E) delay, and jitter. The best scenario possible is clearly the one integrating MEC and SDN approaches, where the overall delay, jitter, and throughput for haptics- attained 2 ms, 0.01 ms, and 1000 packets per second. The results obtained give clear evidence that the integration of, both SDN and MEC, in LTE-A indicates performance improvement, and fulfills the standard requirements in terms of the above KPIs, for realizing a Digital Twin/Tactile Internet-based system.

Abstract Background Debates persist over optimal pelvic girdle reconstruction after acetabular tumor resection, with surgeons grappling between modular and 3D-printed hemipelvic endoprostheses. We hypothesize superior outcomes with 3D-printed versions, yet scarce comparative research exists. This study fills the gap, examining biomechanics and clinical results retrospectively. Methods From February 2017 to June 2021, we retrospectively assessed 32 patients undergoing en bloc resection for malignant periacetabular tumors at a single institution. Primary outcome: limb function. Secondary outcomes: implant precision, hip joint rotation center restoration, prosthesis-bone osteointegration, and complications. Biomechanical characteristics were evaluated through finite element analysis on pelvic defect models. Results In the 3D-printed group, stress distribution mirrored a normal pelvis, contrasting the modular group with elevated overall stress, unstable transitions, and higher stress peaks. The 3D-printed group exhibited superior functional scores (MSTS: 24.3 ± 1.8 vs. 21.8 ± 2.0, p

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging. Results Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo. Conclusions Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis. Graphical abstract

Abstract Background Mitochondria play essential roles in tumorigenesis; however, little is known about the contribution of mitochondrial DNA (mtDNA) to esophageal squamous cell carcinoma (ESCC). Whole-genome sequencing (WGS) is by far the most efficient technology to fully characterize the molecular features of mtDNA; however, due to the high redundancy and heterogeneity of mtDNA in regular WGS data, methods for mtDNA analysis are far from satisfactory. Methods Here, we developed a likelihood-based method dMTLV to identify low-heteroplasmic mtDNA variants. In addition, we described fNUMT, which can simultaneously detect non-reference nuclear sequences of mitochondrial origin (non-ref NUMTs) and their derived artifacts. Using these new methods, we explored the contribution of mtDNA to ESCC utilizing the multi-omics data of 663 paired tumor-normal samples. Results dMTLV outperformed the existing methods in sensitivity without sacrificing specificity. The verification using Nanopore long-read sequencing data showed that fNUMT has superior specificity and more accurate breakpoint identification than the current methods. Leveraging the new method, we identified a significant association between the ESCC overall survival and the ratio of mtDNA copy number of paired tumor-normal samples, which could be potentially explained by the differential expression of genes enriched in pathways related to metabolism, DNA damage repair, and cell cycle checkpoint. Additionally, we observed that the expression of CBWD1 was downregulated by the non-ref NUMTs inserted into its intron region, which might provide precursor conditions for the tumor cells to adapt to a hypoxic environment. Moreover, we identified a strong positive relationship between the number of mtDNA truncating mutations and the contribution of signatures linked to tumorigenesis and treatment response. Conclusions Our new frameworks promote the characterization of mtDNA features, which enables the elucidation of the landscapes and roles of mtDNA in ESCC essential for extending the current understanding of ESCC etiology. dMTLV and fNUMT are freely available from https://github.com/sunnyzxh/dMTLV and https://github.com/sunnyzxh/fNUMT , respectively.

Abstract Objective This study aims to biomimetic design a new 3D-printed lattice hemipelvis prosthesis and evaluate its clinical efficiency for pelvic reconstruction following tumor resection, focusing on feasibility, osseointegration, and patient outcomes. Methods From May 2020 to October 2021, twelve patients with pelvic tumors underwent tumor resection and subsequently received 3D-printed lattice hemipelvis prostheses for pelvic reconstruction. The prosthesis was strategically incorporated with lattice structures and solid to optimize mechanical performance and osseointegration. The pore size and porosity were analyzed. Patient outcomes were assessed through a combination of clinical and radiological evaluations. Results Multiple pore sizes were observed in irregular porous structures, with a wide distribution range (approximately 300–900 μm). The average follow-up of 34.7 months, ranging 26 from to 43 months. One patient with Ewing sarcoma died of pulmonary metastasis 33 months after surgery while others were alive at the last follow-up. Postoperative radiographs showed that the prosthesis’s position was consistent with the preoperative planning. T-SMART images showed that the host bone was in close and tight contact with the prosthesis with no gaps at the interface. The average MSTS score was 21 at the last follow-up, ranging from 18 to 24. There was no complication requiring revision surgery or removal of the 3D-printed hemipelvis prosthesis, such as infection, screw breakage, and prosthesis loosening. Conclusion The newly designed 3D-printed lattice hemipelvis prosthesis created multiple pore sizes with a wide distribution range and resulted in good osteointegration and favorable limb function.

Abstract Background Guidelines on coronary intermediate lesions strongly recommend deferred revascularization after detecting a normal fractional flow reserve (FFR). Researches about triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) on cardiovascular diseases has also been well conducted. However, the association of TG/HDL-C and long-term adverse clinical outcomes remains unknown for patients deferred revascularization following FFR. Methods This study retrospectively included 374 coronary artery disease (CAD) patients with non-significant coronary lesions diagnosed by coronary angiography (CAG) and FFR. The main outcome measure was the combination of major adverse cardiovascular and cerebrovascular events (MACCEs). All patients were categorized into three subgroups in terms of TG/HDL-C tertiles (T1

Background The advent of three‐dimensional (3D)‐printed custom‐made implants has revolutionized orthopaedic surgery, particularly in limb‐ and joint‐sparing surgeries. However, clinical experience in the revision for 3D‐printed implant breakage is lacking, and the revision surgery remains challenging. This study reported the revision of proximal tibial prosthetic reconstruction necessitated by solid‐body breakage of a 3D‐printed implant, aiming to detail the surgical techniques and evaluate postoperative outcomes. Case Presentation A patient diagnosed with osteosarcoma underwent joint‐sparing surgery with a 3D‐printed implant, but implant breakage occurred during subsequent follow‐up. The initial implant was broken into two parts: the proximal implant breakage part (IBP) integrated with the host bone and the distal IBP left in the prosthetic component. Four revision protocols were devised, each based on one of the four hypothesis results of taking out the initial implant. A new custom‐made implant and a series of assistance devices (“positioning devices,” “drill devices,” “tap devices,” and “separator devices”) were specifically prepared for revision surgery. The proximal IBP was taken out from the host bone, but the distal IBP was not taken out from the initial prosthetic component. The patient received the new custom‐made implant for reconstruction, with the knee joint preserved. The patient recovered uneventfully after revision surgery and achieved satisfactory function. The Musculoskeletal Tumor Society was 28 at the last follow‐up. No complications were detected during the follow‐up period. Conclusion Comprehensive preoperative planning and preparation, enabling the surgeon to effectively address intraoperative challenges, are crucial for the successful revision of 3D‐printed implant breakage. It is feasible to re‐implant a 3D‐printed custom‐made implant, demonstrating satisfactory clinical and functional results.

Objective Geographic defect reconstruction in load‐bearing bones presents formidable challenges for orthopaedic surgeon. The use of 3D‐printed personalized implants presents a compelling opportunity to address this issue. This study aims to design, manufacture, and evaluate 3D‐printed personalized implants with irregular lattice porous structures for geographic defect reconstruction in load‐bearing bones, focusing on feasibility, osseointegration, and patient outcomes. Methods This retrospective study involved seven patients who received 3D‐printed personalized lattice implants for the reconstruction of geographic defects in load‐bearing bones. Personalized implants were customized for each patient. Randomized dodecahedron unit cells were incorporated within the implants to create the porous structure. The pore size and porosity were analyzed. Patient outcomes were assessed through a combination of clinical and radiological evaluations. Tomosynthesis‐Shimadzu metal artifact reduction technology (T‐SMART) was utilized to evaluate osseointegration. Functional outcomes were assessed according to the Musculoskeletal Tumor Society (MSTS) 93 score. Results Multiple pore sizes were observed in porous structures of the implant, with a wide distribution range (approximately 300–900 um). The porosity analysis results showed that the average porosity of irregular porous structures was around 75.03%. The average follow‐up time was 38.4 months, ranging from 25 to 50 months. Postoperative X‐rays showed that the implants matched the geographic bone defect well. Osseointegration assessments according to T‐SMART images indicated a high degree of bone‐to‐implant contact, along with favorable bone density around the implants. Patient outcomes assessments revealed significant improvements in functional outcomes, with the average MSTS score of 27.3 (range, 26–29). There was no implant‐related complication, such as aseptic loosening or structure failure. Conclusion 3D‐printed personalized lattice implants offer an innovative and promising strategy for geographic defect reconstruction in load‐bearing bones. This approach has the potential to match the unique contours and geometry of the geographic bone defect and facilitate osteointegration.

Abstract SMEFT Wilson coefficients are subject to various positivity bounds in order to be consistent with the fundamental principles of S-matrix. Previous bounds on dimension-8 SMEFT operators have been obtained using the positivity part of UV partial wave unitarity and form a (projective) convex cone. We derive a set of linear UV unitarity conditions that go beyond positivity and are easy to implement in an optimization scheme with dispersion relations in a multi-field EFT. Using Higgs scattering as an example, we demonstrate how to obtain closed bounds in the space of the three relevant dimension-8 coefficients, making use of the UV unitarity conditions as well as so-called null constraints that arise from full crossing symmetry. Specifically, we show that they are bounded by inequalities schematically going like C < O $$ \mathcal{O} $$ ((4π)2). We compare the newly obtained upper bounds with the traditional perturbative unitarity bounds from within the EFT, and discuss some phenomenological implications of the two-sided positivity bounds in the context of experimental probes of Vector Boson Scattering.

Aiming at the characteristics of various TBM construction risk factors, fuzzy and complex systems, and frequent shutdown accidents, a TBM construction risk analysis methodology based on a fuzzy Bayesian network is proposed. This method mainly selects eighteen risk factors to construct an interpretive structural model. These factors affect the TBM construction from the four aspects of the geological risk, equipment risk, management risk, and technical risk encountered during the construction of a full-face mechanical excavation of the tunnel. A five-level hierarchical directed graph is extracted by matrix operation to determine the relationship between factors. In the case of incomplete data, the Bayesian network model can be established by employing the prior probability to describe the state of the root node through expert scoring, ideal for system predictions lacking data. Finally, the main risk factors affecting the TBM construction are introduced and discussed, and the TBM construction of the West Second Tunnel of the Beijing Water Supply Phase II Project is taken as an example to compare the evaluation results with those of the actual construction status. The obtained results are not much different from those of the actual situation, which proves that the proposed method is scientific and can provide a reliable basis for analogous projects.

Abstract Objective Our study aimed to develop a day anterior cervical discectomy and fusion (ACDF) procedure to treat degenerative cervical spondylosis (DCS). The goal was to analyze its clinical implications, safety, and early effects to provide a better surgical option for eligible DCS patients. Methods A retrospective analysis was performed to identify DCS patients who underwent day ACDF from September 2022 to August 2023. The operative time, intraoperative blood loss, postoperative drainage, preoperative and postoperative visual analog scale (VAS) scores, neck disability index (NDI) scores, Japanese Orthopedic Association (JOA) scores, JOA recovery rate (RR), incidence of dysphagia-related symptoms, 30-day hospital readmission rate, and incidence of other complications were recorded to evaluate early clinical outcomes. Radiography was performed to assess the location of the implants, neurological decompression, and cervical physiological curvature. Results All 33 patients (23 women and 10 men) underwent successful surgery and experienced significant symptomatic and neurological improvements. Among them, 26 patients underwent one-segment ACDF, 5 underwent two-segment ACDF, and 2 underwent three-segment ACDF. The average operative time was 71.1 ± 20.2 min, intraoperative blood loss was 19.1 ± 6.2 mL, and postoperative drainage was 9.6 ± 5.8 mL. The preoperative VAS and NDI scores improved postoperatively (7.1 ± 1.2 vs. 3.1 ± 1.3 and 66.7% ± 4.8% vs. 24.1% ± 2.5%, respectively), with a significant difference (P

Abstract Methanol-to-hydrocarbons (MTH) process has been considered one of the most practical approaches for producing value-added products from methanol. However, the commonly used zeolite catalysts suffer from rapid deactivation due to coke deposition and require regular regeneration treatments. We demonstrate that low-melting-point metals, such as Ga, can effectively promote more stable methanol conversion in the MTH process by slowing coke deposition and facilitating the desorption of carbonaceous species from the zeolite. The ZSM-5 zeolite physically mixed with liquid gallium exhibited an enhanced lifetime in the MTH reaction, which increased by a factor of up to ~14 as compared to the parent ZSM-5. These results suggest an alternative route to the design and preparation of deactivation-resistant zeolite catalysts.

Abstract Background Amino acids (AAs) are one of the primary metabolic substrates for cardiac work. The correlation between AAs and both atrial fibrillation (AF) and aging has been documented. However, the relationship between AAs and age-related AF remains unclear. Methods Initially, the plasma AA levels of persistent AF patients and control subjects were assessed, and the correlations between AA levels, age, and other clinical indicators were explored. Subsequently, the age-related AF mouse model was constructed and the untargeted myocardial metabolomics was conducted to detect the level of AAs and related metabolites. Additionally, the gut microbiota composition associated with age-related AF was detected by a 16S rDNA amplicon sequencing analysis on mouse fecal samples. Results Higher circulation levels of lysine (Student’s t-test, P = 0.001), tyrosine (P = 0.002), glutamic acid (P = 0.008), methionine (P = 0.008), and isoleucine (P = 0.014), while a lower level of glycine (P = 0.003) were observed in persistent AF patients. The feature AAs identified by machine learning algorithms were glutamic acid and methionine. The association between AAs and age differs between AF and control subjects. Distinct patterns of AA metabolic profiles were observed in the myocardial metabolites of aged AF mice. Aged AF mice had lower levels of Betaine, L-histidine, L-alanine, L-arginine, L-Pyroglutamic acid, and L-Citrulline compared with adult AF mice. Aged AF mice also presented a different gut microbiota pattern, and its functional prediction analysis showed AA metabolism alteration. Conclusion This study provided a comprehensive network of AA disturbances in age-related AF from multiple dimensions, including plasma, myocardium, and gut microbiota. Disturbances of AAs may serve as AF biomarkers, and restoring their homeostasis may have potential benefits for the management of age-related AF.

Background Fibrodysplasia ossificans progressiva (FOP) is an extremely rare disease characterized by malformation of the bilateral great toes and progressive heterotopic ossification. The clinical features of FOP occur due to dysfunction of the bone morphogenetic protein (BMP) signaling pathway induced by the mutant activin A type I receptor/activin‐like kinase‐2 (ACVR1/ALK2) which contributes to the clinical features in FOP. Dysregulation of the BMP signaling pathway causes the development of osteochondroma. Poor awareness of the association between FOP and osteochondromas always results in misdiagnosis and unnecessary invasive operation. Case Presentation In this study, we present a case of classical FOP involving osteochondroma. An 18‐year‐old male adolescent, born with deformity of bilateral big toes, complained multiple masses on his back for 1 year. The mass initially emerged with a tough texture and did not cause pain. It was misdiagnosed as an osteochondroma. After two surgeries, the masses became hard and spread around the entire back region. Meanwhile, extensive heterotopic ossification was observed around the back, neck, hip, knee, ribs, and mandible during follow‐up. Osteochondromas were observed around the bilateral knees. No abnormalities were observed in the laboratory blood test results. Whole exome sequencing revealed missense mutation of ACVR1/ALK2 (c.617G > A; p.R206H) in the patient and confirmed the diagnosis of FOP. Conclusion In summary, classical FOP always behaves as a bilateral deformity of the big toes, as well as progressive ectopic ossification and osteochondromas in the distal femur and proximal tibia. An understanding of the association between osteochondromas and FOP aids in diagnosis and avoids unnecessary invasive management in patients.

The surface of A286 alloy easily undergoes passivation， making it difficult to deposit a phosphating film on surface of A286 alloy using the traditional chemical phosphating method.However， electrochemical phosphating can avoid the inhibitory effect of the passivation film on the phosphating reaction.Therefore， studying the influence of phosphating current density on the microstructure and properties of the phosphating film is necessary.In this study， a compact phosphating film with high film-base adhesion strength was formed on the surface of A286 alloy using electrochemical phosphating for the first time.The potential-time (φ-t) curves of the phosphating process under various current densities were mapped using an electrochemical workstation to examine the characteristics of the growth process of electrochemical phosphating films.The microstructure and morphology of the phosphating film were observed using a scanning electron microscope (SEM).Using an energy dispersive spectrometer (EDS) to analyze the chemical composition of different areas of the phosphating film.X-ray diffraction (XRD) was employed to study the phase structure of the phosphating film， and the adhesion strength between the phosphating film and substrate was measured using a scratch tester.Results showed that the deposition mode of the electrochemical phosphating film on A286 alloy occurred through layer-by-layer growth stacking.At low current densities， the phosphating film was formed as a single Hopeite phase with a coarse and loose structure， and the bonding force between the film and the substrate was about 6 N.As the phosphating current density was increased， the phosphating film gradually transformed into a Zn＋Hopeite multiphase， resulting in a refined and dense microstructure， and the adhesion strength between the film and substrate was improved.At a cathode current density of 160 mA/cm2， the bonding force between the membrane and substrate exceeded 60 N.Generally，the increase in phosphating current density was found to be beneficial for the densification of the electrochemical phosphating film and enhanced both the adhesion strength between the film and substrate and wear resistance of the film.

This is an article in the field of earth sciences. The newly discovered Maoping graphite deposit is a super-large crystalline graphite deposit that is located in the middle-northern section of the Kang-Dian fault-uplift belt on the western margin of the Upper Yangtze paleo-continent, and the research on the source of mineralization and its mineralization age is relatively weak. The orebodies occur in the epimetamorphic rocks of Mesoproterozoic Tianbaoshan Formation. In this paper, the geochemical characteristics of major ores, trace amounts and rare earth elements were mainly studied. The results show that the original rock of the ore-bearing rock layer is parametamorphic rock, a set of carbonaceous quartz-bearing siltstone, which is deposited in an oxygen-deficient environment. The characteristics of trace elements indicate that the original rock of the ore body is formed by the deposition of offshore terrigenous clasts. The ores show sedimentary characteristics of coastal tidal flat facies, with an average ΣREE of 158 g/t, average δ Ce value of 0.63 (weak negative anomaly), and an average δ Eu value of 0.69 (negative abnormaly). The graphite ore body has a δ13C value of -28.35‰～-29.08‰, with an average of -28.59‰, indicating that the mineralized carbon is dominated by organic carbon. The LA-MC-ICP-MS Zircon U-Pb of amphibole zircon from Xijie hornblende diorite Zircon is (823.4±3.6) Ma, which is later than the formation era of volcanic rocks of the Tianbaoshan Formation (954 Ma), representing the time of superposition metamorphism of graphite. In summary,the genetic type of the ore deposit is sedimentary- metamorphism and its metamorphism may include the regional dynamic metamorphism of Jinning period that is superimposed by contact metamorphism.

Extreme meteorological disasters such as typhoons pose a serious threat to the safety of engineering structures. Therefore, the refined simulation on the near-surface atmospheric boundary layer (ABL) is valuable for civil engineering. Large-eddy simulation (LES) implemented in the weather research and forecating (WRF) model has the advantages of multiple options of numerical schemes and high accuracy. It is generally suitable for the refined simulation of the near-surface wind field, although the performance of simulation results is closely related to the numerical methods. This paper assesses the impacts of vital parameters regarding subfilter-scale (SFS) stress models, mesh size, and spatial difference schemes within WRF-LES to simulate the ideal ABL in order to figure out appropriate numerical schemes for the refined simulation of the near-surface wind field. The wind field characteristics are addressed and analyzed such as mean wind speed profile, turbulence intensity profile, and power of spectrum. Comparisons of simulation results among different SFS stress models indicate that the nonlinear backscatter and anisotropy one (NBA1) SFS stress model can effectively improve the accuracy of simulation in the near-surface wind profiles. Investigations of mesh resolution effects indicate that the nonuniformly refined vertical grid near the surface agrees much better with the expected profiles and reduces the expenditure of computational resources. Furthermore, the results show that the even-order spatial difference schemes produce more small-scale turbulent structures than the odd-order difference schemes. The numerical methods of WRF-LES proposed can provide a technical reference for refined simulation of the near-surface wind field and typhoon boundary layer.

Background Intercalary reconstruction for patients with short residual bone segments remains challenging. Three‐dimensional (3D)‐printed custom‐made porous implants are a promising technique for short‐segment fixation in these patients. This study aims to evaluate the efficiency of 3D‐printed custom‐made porous components (3DCPCs) for short‐segment fixation, focusing on prosthesis survivorship, radiographic results, and potential complications. Methods This retrospective study involved 39 patients who underwent intercalary prosthetic reconstruction with 3DCPCs after tumor resection of the femur, tibia, or humerus from June 2015 to October 2020. Segment bone loss involved the femur (n = 15), tibia (n = 16), and humerus (n = 8), leaving 78 residual bone segments. There were 46 short segments requiring 46 3DCPCs and 32 segments with the ability to accommodate 32 off‐the‐shelf standard uncemented stems for prosthesis fixation. Clinical and functional outcomes were evaluated. Prosthesis‐overall survivorship and prosthesis‐specific survivorship were analyzed using Kaplan–Meier survival analysis. Radiographic results and modes of failure of using this technique were also examined. Results The mean follow‐up was 41 months. The prosthesis‐overall survivorship was 87.2% and 84.6% at 2 and 5 years, respectively. The prosthesis‐specific survivorship was 92.1% and 89.5% at 2 and 5 years, respectively. There was not a substantial difference in prosthesis survivorship among the femur, tibia, and humerus. The average MSTS score was 26.2, ranging from 22 to 28. The radiographic evaluation results revealed excellent or good interface (38/46) in most of the 46 porous components. A total of 38 of 46 bone segments’ remolding demonstrated no change. In total, seven patients (16.3%) had complications requiring further surgery. Conclusion The prosthesis survivorship of using 3DCPCs for short‐segment fixation is similar or better compared to other studies involving intercalary prosthetic reconstruction with short‐segment fixation. Radiographic evaluation revealed good osteointegration and avoidance of stress shielding. Overall, intercalary prosthetic reconstruction with 3DCPC is a feasible modality for patients with short residual bone segments after tumor resection.

The classification of Remote Sensing Images (RSIs) poses a significant challenge due to the presence of clustered ground objects and noisy backgrounds. While many approaches rely on scaling models to enhance accuracy, the deployment of RSI classifiers often requires substantial computational and storage resources, thus necessitating the use of lightweight algorithms. In this paper, we present an efficient and robust knowledge transfer network named ERKT-Net, which is designed to provide a lightweight yet accurate Convolutional Neural Network (CNN) classifier. This method utilizes innovative yet simple concepts to better accommodate the inherent nature of RSIs, thereby significantly improving the efficiency and robustness of traditional Knowledge Distillation (KD) techniques developed on ImageNet-1K. We evaluated ERKT-Net on three benchmark RSI datasets and found that it demonstrated superior accuracy and a very compact volume compared to 40 other advanced methods published between 2020 and 2023. On the most challenging NWPU45 dataset, ERKT-Net outperformed other KD-based methods with a maximum Overall Accuracy (OA) value of 22.4%. Using the same criterion, it also surpassed the first-ranked multi-model method with a minimum OA value of 0.7 but presented at least an 82% reduction in parameters. Furthermore, ablation experiments indicated that our training approach has significantly improved the efficiency and robustness of classic DA techniques. Notably, it can reduce the time expenditure in the distillation phase by at least 80%, with a slight sacrifice in accuracy. This study confirmed that a logit-based KD technique can be more efficient and effective in developing lightweight yet accurate classifiers, especially when the method is tailored to the inherent characteristics of RSIs.

Abstract An accurate quantification of global methane sources and sinks is imperative for assessing realistic pathways to mitigate climate change. A key challenge of quantifying the Global Methane Budget (Saunois et al., 2020, https://doi.org/10.5194/essd‐12‐1561‐2020) is the lack of consistency in uncertainties between sectors. Here we provide a new perspective on bottom‐up (BU) and top‐down (TD) methane uncertainties by using an expert opinion analysis based on a questionnaire conducted in 2021. Expectedly, experts rank highest uncertainty and lowest confidence levels in the Global Methane Budget related to natural sources in BU budgets. Here, we further reveal specific uncertainty types and introduce a ranking system for uncertainties in each sector. We find that natural source uncertainty is related particularly to driver data uncertainty in freshwater, vegetation, and coastal/ocean sources, as well as parameter uncertainty in wetland models. Reducing uncertainties, most notably in aquatic and wetland sources will help balance future BU and TD global methane budgets. We suggest a new methane source partitioning over gradients of human disturbance and demonstrate that 76.3% (75.8%–79.4%) or 561 (443–700) Tg CH4 yr−1 of global emissions can be attributed to moderately impacted, man‐made, artificial, or fully anthropogenic sources and 23.7% (20.6%–24.2%) or 174 (115–223) Tg CH4 yr−1 to natural and low impacted methane sources. Finally, we identify current research gaps and provide a plan of action to reduce current uncertainties in the Global Methane Budget.

IntroductionBorderline Personality Disorder (BPD) traits play a crucial role in the prognosis of psychiatric disorders, as well as in assessing risks associated with negativity and impulsivity. However, there is a lack of data regarding the distribution characteristics of BPD traits and symptoms within clinical populations.MethodsA total of 3015 participants (1321 males, 1694 females) were consecutively sampled from outpatients at the psychiatric and psycho-counseling clinics at the Shanghai Mental Health Center. BPD symptoms were assessed using a self-reported personality diagnostic questionnaire. Having BPD traits is defined as having five or more positive items in self-reported BPD characteristics. Participants were stratified into male and female groups, age groups, and diagnostic groups (schizophrenia, mood disorders, anxiety disorders). Exploratory factor analysis using principal components analysis was conducted. Three factors were identified: “F1: Affective Instability and Impulsivity”, “F2: Interpersonal Unstable and Extreme Reactions”, and “F3: Identity Disturbance”.ResultsAmong 3015 participants, 45.9% of the patients self-reported BPD traits. Comparing of male and female patients, there was no statistically significant difference in the occurrence rate of BPD traits (χ2 = 1.835, p=0.176). However, in terms of symptoms, female patients reported more symptoms than male patients. Female patients also exhibited more pronounced features on F2 compared to male patients (t =-1.972, p=0.049). There is a general decrease in BPD traits, symptoms, and factors with increasing age. Specifically, the proportion of positive BPD traits is approximately halved before the age of 30 and decreases to around one-third after the age of 30. BPD traits were most common in the Mood Disorders group at 55.7%, followed by the Anxiety Disorders group at 44.4%, and Schizophrenia group at 41.5% (χ2 = 38.084, p

Quantitative Real-time PCR (qRT-PCR) is one of the most widely used methods for gene quantification because it is extremely sensitive, can be highly sequence specific, and has high precision while being easily reproducible in samples. The stability of the reference genes used for data normalization is crucial for exact experimental results and conclusions. In this study, qRT-PCR was used to analyze the expression of eight candidate reference genes including β-actin (ACTB), α-tubulin (TUBA), Elongation factor-1-α (EF1A), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH1, GAPDH2), Hypoxanthine guanine phosphoribosyl transferase1 (HPRT), Ribosomal protein L7 (RPL7), and RNA polymerase II (RNA PoL Ⅱ) in largemouth bass. The expression and stability of above genes were evaluated among eight tissues with or without largemouth bass virus (LMBRaV) infection and assessed using BestKeeper, GeNorm, NormFinder statistical softwares and comparative Ct method, and then analyzed the comprehensive ranking by ReFinder. Our results showed that ACTB was identified as the most suitable genes of different tissues, while TUBA was ranked as the best reference gene in tissues infection with LMBRaV. To verify the screened reference genes, the expression pattern of IFN in spleen during LMBRaV infection was examined. This study provides useful information for gene expression characterization using qRT-PCR, which will benefit for future studies of gene regulation in largemouth bass.

Analytical expressions of the electric field, the centriod, the beam half width, and the linear momentum of the fractional Fourier transform (FrFT) of an Airyprime beam are derived, respectively. The relation between the centriods or the beam half widths of an Airyprime beam in the exit and the input planes of a FrFT system is also presented. The effect of the fractional order p on the FrFT of an Airyprime beam is investigated in detail and graphically presented. The cycle of the light intensity, the centriod, and the linear momentum of an Airyprime beam in the exit plane of a FrFT system versus p is 4, while the cycle of the beam half width versus p is 2. This research in the FrFT of an Airyprime beam has potential applications. First, special laser beams with different shapes can be generated by controlling p. Then, the FrFT of an Airyprime beam can be used as an optical switch due to the reversal of the positive and the negative signs of the linear momentum in the first and the last half cycle. Finally, the mirror transformation of the spatial orientation of the beam spot for the FrFT of an Airyprime can be used in optical micro-manipulation.

IntroductionDesmoid fibromatosis is an aggressive fibroblastic neoplasm with a high propensity for local recurrence. Targeted therapy for Desmoid fibromatosis represents a novel avenue in systemic treatment. Anlotinib, a novel multitargeted angiogenesis inhibitor, represents a novel approach for targeted therapy. Therefore, this study aims to assess the efficacy and safety of anlotinib in patients with Desmoid fibromatosis.MethodsWe retrospectively gathered the clinical medical records of Desmoid fibromatosis patients who underwent anlotinib treatment between June 2019 and November 2023 at our center. Anlotinib was initiated at a daily dose of 12 mg and adjusted based on drug-related toxicity. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors 1.1 criteria. Progression-free survival served as the primary endpoint and was analyzed utilizing the Kaplan–Meier method.ResultsIn total, sixty-six consecutive patients were enrolled. No patients achieved a complete response; however, fourteen patients (21.21%) exhibited a partial response, while forty-six patients (70%) experienced disease stability. Progressive disease was observed in 6 patients (9.10%), and the progression-free survival rates at 12 and 36months were 89.71% and 82.81%, respectively. The disease control rate was 90.91%, while the objective response rate was 21.21%.ConclusionAnlotinib proves effective in managing recurrent and symptomatic patients with Desmoid fibromatosis. However, the toxicity profile of anlotinib presents a higher risk of Hand-Foot Skin Reaction and hypertension. Therefore, given that 41.67% of patients were subjected to dose adjustments associated with the initial dose of 12 mg, implementing dosage reductions may help balance efficacy with side effects.

IntroductionBiliary Infection in patients is a common and important phenomenon resulting in severe complications and high morbidity, while the distributions and drug resistance profiles of biliary bacteria and related risk factors are dynamic. This study explored the characteristics of and risk factors for biliary infection to promote the rational use of antibiotics in clinically.MethodsBacterial identification and drug susceptibility testing were completed using the Vitek 2 Compact analysis system. The distribution and antibiotic-resistant characteristics of 3,490 strains of biliary bacteria in patients at Nankai Hospital from 2019 to 2021 were analyzed using Whonet 5.6 and SPSS 26.0 software. We then retrospectively analyzed the clinical data and risk factors associated with 2,340 strains of Gram-negative bacilli, which were divided into multidrug-resistant bacteria (1,508 cases) and non-multidrug-resistant bacteria (832 cases) by a multivariate Cox regression model.Results and discussionA total of 3,490 pathogenic bacterial strains were isolated from bile samples, including 2,340 (67.05%) Gram-negative strains, 1,029 (29.48%) Gram-positive strains, and 109 (4.56%) fungal strains. The top five pathogenic bacteria were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, Enterococcus faecalis, and Pseudomonas aeruginosa. The rate of Escherichia coli resistance to ciprofloxacin increased (p