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How disorder affects magnetic ordering is always an intriguing question, and it becomes even more interesting in the recently rising high entropy oxides due to the extremely high disorder density. However, due to the lack of high-quality single crystal samples, the strong compositional disorder effect on magnetic transition has not been deeply investigated. In this work, we have successfully synthesized high-quality single crystalline high entropy spinel ferrites (Mg 0.2 Mn 0.2 Fe 0.2 Co 0.2 Ni 0.2 ) x Fe 3- x O 4 . Our findings from high-temperature magnetization and neutron diffraction experiments showed ferrimagnetic transitions at 748, 694, and 674 K for x values of 1, 1.5, and 1.8, respectively. Notably, the magnetic transition almost showed no broadening for x values of 1 and 1.5, compared to Fe 3 O 4 . Extended X-ray absorption fine structure measurements provided insights into the elemental distribution among the octahedral and tetrahedral sites. The random distribution of elements across these sites reduced the formation of local clusters and short-range orders, enhancing sample homogeneity and preserving the sharpness of the magnetic transition, despite bond length variation. Our study not only marks the first successful synthesis of an HEO bulk single crystal exhibiting long-range magnetic order but also sheds light on the interaction between high configurational entropy and magnetic orderings. This opens new avenues for future research and applications of magnetic high entropy oxides.

Background: It is unknown how blood pressure (BP) relates to stroke risk across levels of hypertension daily dose (HDD)-quantified antihypertensive medication intensity., Methods and Results: The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study enrolled 30 239 participants from the 48 contiguous US states in 2003 to 2007 with in-person follow-up in 2013 to 2016 (Visit 2). We included those without prior stroke at Visit 2, treating this visit as T 0 . Biannual phone calls and medical record review ascertained incident stroke events. Cox proportional hazard models estimated the hazard ratio (HR) of incident stroke by treatment intensity defined by systolic BP stages and HDD groupings. There were 344 stroke events over a median 5.5 years. Relative to systolic BP <120 mm Hg and no antihypertensive medications, the stroke HR was 2.86 (95% CI, 1.68-4.85) for systolic BP 140 to 159 mm Hg and HDD tertile 2, 2.33 (1.37-3.97) for systolic BP 140 to 159 mm Hg and HDD tertile 3, 3.08 (1.20-7.88) for systolic BP ≥160 mm Hg and HDD tertile 2, and 3.66 (1.61-8.30) for systolic BP ≥160 mm Hg and HDD tertile 3. Stroke risk was similar across HDD levels for people with systolic BP <140 mm Hg., Conclusions: Among adults without prior stroke, systolic BP ≥140 mm Hg and HDD tertile ≥2 was associated with greater stroke risk. For adults with BP <140 mm Hg, stroke risk was similar despite cumulative dose of antihypertensive medications used. These findings support the practice of BP-lowering medications to mitigate stroke risk.

Traditional chemiluminescence (CL) imaging immunoassays usually rely on natural enzymes as catalytic probes, which has hampered their extensive application due to the susceptibility to inactivation of natural enzymes. In response, a gold brocade coated CoFe Prussian blue analogue (CoFe PBA@Au brocade) with enhanced peroxidase-like activity was synthesized and utilized as a powerful label probe for constructing a highly sensitive CL imaging immunosensor targeting disease biomarkers with excellent performance. This research offers a universal strategy for enhancing the sensitivity of CL imaging immunoassays and further expands the application of PBA nanozymes.

Calcium-dependent protein kinases (CDPKs) are pivotal signaling transduction enzymes in plants, especially responsive to diverse stress, including herbivory. In this study, through comprehensive analysis of CDPK gene family in upland cotton, we showed that GhCPKs are widely expressed in multiple tissues of cotton and positively respond to various biotic and abiotic stress. We developed a strategy for screening insect-resistant genes based on the CRISPR/Cas9 mutant library of GhCPKs. The library contains 82 members of the GhCPKs using 246 sgRNAs to generate 518 independent T0 plants. The coverage rate of target genes reached to 86.18%, the genome editing rate reached to 89.49%, and the editing heritability reached 82%. Through field insect bioassay, 14 GhCPK mutants resistant or susceptible to insect were identified. The most obvious insect-resistant mutant, cpk33/74 (simultaneously knocking out the homologous genes GhCPK33 and GhCPK74), was selected for further study. Oral secretions (OS) from Spodoptera litura induced a rapid influx of Ca 2+ in cpk33/74 leaves, resulting in a significant increase in jasmonic acid (JA) content. S-adenosylmethionine synthase (SAMS) is an important protein involved in plant stress response, protein interaction experiments provided evidence of interactions between GhCPK33 and GhCPK74 with GhSAMS1 and GhSAM2, respectively. Additionally, silencing GhSAMS1 and GhSAM2 in cotton using VIGS resulted in decreased defense against S. litura. This study provides an effective strategy for constructing a mutant library of gene families in polyploid plant species and valuable insights into the role of CDPKs in the interaction between plants and herbivorous insects., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

It takes more than 20 years for normal colorectal mucosa to develop into metastatic carcinoma. The long time window provides a golden opportunity for early detection to terminate the malignant progression. Here, we aim to enable liquid biopsy of T1a stage colorectal cancer (CRC) and precancerous advanced adenoma (AA) by profiling circulating small extracellular vesicle (sEV)-derived RNAs. We exhibited a full RNA landscape for the circulating sEVs isolated from 60 participants. A total of 58,333 annotated RNAs were detected from plasma sEVs, among which 1,615 and 888 sEV-RNAs were found differentially expressed in plasma from T1a stage CRC and AA compared to normal controls (NC). Then we further categorized these sEV-RNAs into six modules by a weighted gene coexpression network analysis and constructed a 60-gene t-SNE model consisting of the top 10 RNAs of each module that could well distinguish T1a stage CRC/AA from NC samples. Some sEV-RNAs were also identified as indicators of specific endoscopic and morphological features of different colorectal lesions. The top-ranked biomarkers were further verified by RT-qPCR, proving that these candidate sEV-RNAs successfully identified T1a stage CRC/AA from NC in another cohort of 124 participants. Finally, we adopted different algorithms to improve the performance of RT-qPCR-based models and successfully constructed an optimized classifier with 79.3% specificity and 99.0% sensitivity. In conclusion, circulating sEVs of T1a stage CRC and AA patients have distinct RNA profiles, which successfully enable the detection of both T1a stage CRC and AA via liquid biopsy., Competing Interests: LM, FB, JM, QG, XL, SZ, SZ No competing interests declared, XL, LZ, ZL are employed by Echo Biotech Co, Ltd. The authors have no other competing interests to declare, (© 2023, Min et al.)

Background: Effective response and reducing the burden of family care for children with cancer is critical, and China currently lacks a specific assessment tool., Aims: This study aimed to translate and validate the Caregiving Burden Scale for Family Caregivers of Children with Cancer (CBSFC-CC) and then test and implement the tool., Methods: According to the Beaton cross-cultural debugging guide, preliminary Chinese version of CBSFC-CC scale was formed, which was suitable for Chinese language environment and clinical context. Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were performed to verify structural validity. Convergent validity, discriminant validity and reliability were also conducted., Results: A total of 529 family caregivers of children with cancer participated in the survey. EFA extracts and combines four factors and explained 65.80% of the total variation. CFA proved that all the goodness-of-fit indicators were acceptable. The Cronbach's alpha of the Chinese version of CBSFC-CC was .96, and the test-retest reliability coefficient was .95. Four dimensions and 29 items were identified in the final Chinese version of CBSFC-CC., Conclusion: The chinese version CBSFC-CC is scientifically reasonable and has good reliability and validity, which can be applied to the investigation of the nursing burden of family caregivers of children with cancer in China., (© 2024. The Author(s).)

Diabetic kidney disease (DKD) is a microvascular complication of diabetes, and glomerular endothelial cell (GEC) dysfunction is a key driver of DKD pathogenesis. Krüppel-like factor 2 (KLF2), a shear stress-induced transcription factor, is among the highly regulated genes in early DKD. In the kidney, KLF2 expression is mostly restricted to endothelial cells, but its expression is also found in immune cell subsets. KLF2 expression is upregulated in response to increased shear stress by the activation of mechanosensory receptors but suppressed by inflammatory cytokines, both of which characterize the early diabetic kidney milieu. KLF2 expression is reduced in progressive DKD and hypertensive nephropathy in humans and mice, likely due to high glucose and inflammatory cytokines such as TNF-α. However, KLF2 expression is increased in glomerular hyperfiltration-induced shear stress without metabolic dysregulation, such as in settings of unilateral nephrectomy. Lower KLF2 expression is associated with CKD progression in patients with unilateral nephrectomy, consistent with its endoprotective role. KLF2 confers endoprotection by inhibition of inflammation, thrombotic activation, and angiogenesis, and thus KLF2 is considered a protective factor for cardiovascular disease (CVD). Based on similar mechanisms, KLF2 also exhibits renoprotection, and its reduced expression in endothelial cells worsens glomerular injury and albuminuria in settings of diabetes or unilateral nephrectomy. Thus KLF2 confers endoprotective effects in both CVD and DKD, and its activators could potentially be developed as a novel class of drugs for cardiorenal protection in diabetic patients.

Poisson's ratio in auxetic materials shifts from typically positive to negative, causing lateral expansion during axial tension. This scale-independent characteristic, originating from tailored architectures, exhibits specific physical properties, including energy adsorption, shear resistance, and fracture resistance. These metamaterials demonstrate exotic mechanical properties with potential applications in several engineering fields, but biomedical applications seem to be one of the most relevant, with an increasing number of articles published in recent years, which present opportunities ranging from cellular repair to organ reconstruction with outstanding mechanical performance, mechanical conduction, and biological activity compared with traditional biomedical metamaterials. Therefore, focusing on understanding the potential of these structures and promoting theoretical and experimental investigations into the benefits of their unique mechanical properties is necessary for achieving high-performance biomedical applications. Considering the demand for advanced biomaterial implants in surgical technology and the profound advancement of additive manufacturing technology that are particularly relevant to fabricating complex and customizable auxetic mechanical metamaterials, this review focuses on the fundamental geometric configuration and unique physical properties of negative Poisson's ratio materials, then categorizes and summarizes auxetic material applications across some surgical departments, revealing efficacy in joint surgery, spinal surgery, trauma surgery, and sports medicine contexts. Additionally, it emphasizes the substantial potential of auxetic materials as innovative biomedical solutions in orthopedics and demonstrates the significant potential for comprehensive surgical application in the future., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

The distal femur is one of the most common sites for primary bone tumors. As the tumor progresses and bone destruction worsens, it can severely affect knee function and even pose a threat to life. In cases where only one condyle is affected and requires resection, preserving the healthy contralateral condyle can substantially enhance the biomechanics of the knee. Furthermore, preserving bone stock may enable future salvage procedures in the event of initial surgery failure, be it from fractures or osteoarthritis. Distal femoral unicondyle resection can offer better functional outcomes in select cases. However, it is essential to prioritize oncological safety with adequate margins over short-term knee function. Currently, the primary methods for reconstruction after the excision of a unicondylar tumor include allograft transplantation (bi- or uni-condylar) and prosthetic or allograft-prosthesis composite replacement (APC). However, there is currently some controversy regarding the optimal surgical reconstruction method, and a consensus within the academic community has yet to be reached. Moreover, due to the rarity of bone tumors, extensive clinical data from a single center is limited. Current studies are mainly retrospective and single-center, lacking sufficient cases and follow-up duration. This article reviews surgical reconstruction after solitary condylar excision in distal femoral tumors. It summarizes, compares, and analyzes mainstream reconstruction methods, exploring their technical details and clinical outcomes to highlight their potential in bone oncology., (© 2024 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: The intensive use of antibiotics has resulted in strong natural selection for the evolution of antimicrobial resistance (AMR), but whether, and under what circumstances, the removal of antibiotics would result in a rapid reduction in AMR has been insufficiently explored. We aimed to test the hypothesis that in the simple, yet common, case of AMR conferred by a single gene, removing antibiotics would quickly reduce the prevalence of resistance if the AMR gene imposes a high fitness cost and costless resistance is extremely rare among its proximal mutants., Methods: In this genetic study, to test our hypothesis, we used the mcr-1 gene in Escherichia coli, which confers resistance to the last-resort antibiotic colistin, as a model. A high-throughput reverse genetics approach was used to evaluate mcr-1 variants for their fitness cost and resistance levels relative to a non-functional construct, by measuring relative growth rates in colistin-free media and at 2 μg/mL and 4 μg/mL colistin. We identified costless resistant mcr-1 mutants, and examined their properties within the context of the sequential organisation of mcr-1's functional domains as well as the evolutionary accessibility of these mutations. Finally, a simple population genetic model incorporating the measured fitness cost was constructed and tested against previously published real-world data of mcr-1 prevalence in colonised inpatients in China since the 2017 colistin ban in fodder additives., Findings: We estimated the relative growth rates of 14 742 mcr-1 E coli variants (including the wild type), 3449 of which were single-nucleotide mutants. E coli showed 73·8% less growth per 24 h when carrying wild-type mcr-1 compared with the non-functional construct. 6252 (42·4%) of 14 741 mcr-1 mutants showed colistin resistance accompanied by significant fitness costs, when grown under 4 μg/mL colistin selection. 43 (0·3%) mcr-1 mutants exhibited costless resistance, most of which contained multiple mutations. Among the 3449 single mutants of mcr-1, 3433 (99·5%) had a fitness cost when grown in colistin-free media, with a mean relative growth of 0·305 (SD 0·193) compared with the non-functional variant. 3059 (88·7%) and 1833 (53·1%) of 3449 single mutants outgrew the non-functional mcr-1 in the presence of 2 μg/mL and 4 μg/mL colistin, respectively. Single mutations that gave rise to costless mutants were rare in all three domains of mcr-1 (transmembrane domain, flexible linker, and catalytic domain), but the linker domain was enriched with cost-reducing and resistance-enhancing mutations and depleted with cost-increasing mutations. The population genetics model based on the experimental data accurately predicts the rapid decline in mcr-1 prevalence in real-world data., Interpretation: Many identified costless resistant variants that consist of multiple mutations are unlikely to evolve easily in nature. These findings for colistin and mcr-1 might be applicable to other cases in which AMR entails a substantial fitness cost that cannot be mitigated in proximal mutants., Funding: National Natural Science Foundation of China, and National Key Research and Development Program of China., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Resection of pelvic bone tumours and subsequent pelvic girdle reconstruction pose formidable challenges due to the intricate anatomy, weight-bearing demands, and significant defects. 3D-printed implants have improved pelvic girdle reconstruction by enabling precise resections with customized guides, offering tailored solutions for diverse bone defect morphology, and integrating porous surface structures to promote osseointegration. Our study aims to evaluate the long-term efficacy and feasibility of 3D-printed hemipelvic reconstruction following resection of malignant pelvic tumours., Methods: A retrospective review was conducted on 96 patients with primary pelvic malignancies who underwent pelvic girdle reconstruction using 3D-printed custom hemipelvic endoprostheses between January 2017 and May 2022. Follow-up duration was median 48.1 ± 17.9 months (range, 6 to 76 months). Demographic data, imaging examinations, surgical outcomes, and oncological evaluations were extracted and analyzed. The primary endpoints included oncological outcomes and functional status assessed by the Musculoskeletal Tumor Society (MSTS-93) score. Secondary endpoints comprised surgical duration, intraoperative bleeding, pain control and complications., Results: In 96 patients, 70 patients (72.9%) remained disease-free, 15 (15.6%) had local recurrence, and 11 (11.4%) succumbed to metastatic disease. Postoperatively, function improved with MSTS-93 score increasing from 12.2 ± 2.0 to 23.8 ± 3.8. The mean operating time was 275.1 ± 94.0 min, and the mean intraoperative blood loss was 1896.9 ± 801.1 ml. Pain was well-managed, resulting in substantial improvements in VAS score (5.3 ± 1.8 to 1.4 ± 1.1). Complications occurred in 13 patients (13.5%), including poor wound healing (6.3%), deep prosthesis infection (4.2%), hip dislocation (2.1%), screw fracture (1.0%), and interface loosening (1.0%). Additionally, all patients achieved precise implantation of customized prosthetics according to preoperative plans. T-SMART revealed excellent integration at the prosthesis-bone interface for all patients., Conclusion: The use of a 3D-printed custom hemipelvic endoprosthesis, characterized by anatomically designed contours and a porous biomimetic surface structure, offers a potential option for pelvic girdle reconstruction following internal hemipelvectomy in primary pelvic tumor treatment. Initial results demonstrate stable fixation and satisfactory mid-term functional and radiographic outcomes., (© 2024. The Author(s).)

Background and Purpose: This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy., Methods: Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed., Results: Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study., Conclusion: Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Uremia-associated immunodeficiency, mainly characterized by T cell dysfunction, exists in patients on maintenance hemodialysis (MHD) and promotes systemic inflammation. However, T cell senescence, one of the causes of T cell dysfunction, has not been clearly revealed yet. In this cross-sectional research, we aimed to study the manifestation of T cell premature senescence in MHD patients and further investigate the associated clinical factors., Methods: 76 MHD patients including 33 patients with cardiovascular diseases (CVD) and 28 patients with arteriovenous fistula (AVF) event history were enrolled in this study. Complementarity determining region 3 (CDR3) of T cell receptor (TCR) was analyzed by immune repertoire sequencing (IR-Seq). CD28- T cell subsets and expression of senescence marker p16 and p21 genes were detected by multicolor flow cytometry and RT-qPCR, respectively., Results: MHD patients had significantly decreased TCR diversity (P < 0.001), increased CDR3 clone proliferation (P = 0.001) and a left-skewed CDR3 length distribution. The proportion of CD4 + CD28- T cells increased in MHD patients (P = 0.014) and showed a negative correlation with TCR diversity (P = 0.001). p16 but not p21 expression in T cells was up-regulated in MHD patients (P = 0.039). Patients with CVD exhibited increased expression of p16 and p21 genes (P = 0.010 and 0.004, respectively), and patients with AVF events showed further TCR diversity and evenness reduction (P = 0.002 and 0.017, respectively) compared to patients without the comorbidities. Moreover, age, average convection volume, total cholesterol, high-density lipoprotein cholesterol and transferrin saturation were associated with TCR diversity or CD4 + CD28- T cell proportion (P < 0.05)., Conclusions: MHD patients undergo T cell premature senescence characterized by significant TCR diversity reduction and repertoire skew, as well as accumulation of the CD4 + CD28- subset and up-regulation of p16 gene. Patients with CVD or AVF events show higher level of immunosenescence. Furthermore, T cell senescence in MHD patients is associated with blood cholesterol and uremic toxin retention, suggesting potential intervention strategies in the future., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Specific types of gastric tumors, including gastric linitis plastica and lymphoma, may cause extensive deep-layer infiltration, impeding an accurate diagnosis with endoscopic biopsy. This study aims to evaluate the efficacy of endoscopic ultrasound (EUS)-guided bite-on-bite biopsy and EUS-guided fine-needle aspiration (EUS-FNA) in diagnosing gastric malignancies with negative endoscopic biopsies., Methods: We retrospectively analyzed suspicious malignant gastric lesion cases in our hospital from October 2017 to August 2023. Clinical manifestations, radiographical examinations, endoscopic examinations, histopathological results, and therapeutic strategies were recorded and analyzed., Results: Forty malignant gastric tumor cases with negative endoscopic biopsies were incorporated into our study. EUS-guided bite-on-bite biopsy was performed in 16 cases exclusively, whereas 17 patients received EUS-FNA exclusively, and seven patients underwent both simultaneously. Among the 23 patients who received the EUS-guided bite-on-bite biopsy, 22 (95.7%) were diagnosed with malignancies. Among the 24 patients who received EUS-FNA, a total of 19 cases with malignancies (79.2%) were confirmed by EUS-FNA ( p  = 0.11): 13 gastric adenocarcinomas, five metastatic malignancies, and one malignant stromal tumor. No adverse events were observed in any of the cases., Conclusions: EUS-guided bite-on-bite biopsy and EUS-FNA possess their advantages and disadvantages. EUS-guided bite-on-bite biopsy could serve as a reliable diagnostic method for shallow lesions with negative malignant endoscopic biopsies.

Aim: In situ vaccination, a kind of therapeutic cancer vaccine, can be realized by radiotherapy and intratumoral immune injection. This study combines intratumoral injection, radiotherapy and PD-1 blockade for synergistic antitumor effect. Materials & methods: Patients with advanced solid tumors who are unresponsive or intolerant to standard treatment will be treated with hypofractionated radiotherapy, intratumoral injection of FOLactis, PD-1 blockade. The primary end point is to observe the efficacy and safety, with the secondary end point to evaluate abscopal effects and the correlation between the immunological rationale and efficacy. Discussion: The combined regimen will be utilized to trigger antitumor immunity and is expected to be feasible and effective and provide a novel option for the comprehensive treatment of cancer. Clinical Trial Registration: ChiCTR2200060660 (ChiCTR.gov.cn).

Methane emissions from ruminants significantly contribute to greenhouse gases. This study explores the methane mitigation effect and mechanism of S. mcclurei through in vitro rumen fermentation, aiming to establish its potential as a feed additive. We investigated the effects of freeze-dried and dried S. mcclurei at supplementation levels of 2%, 5%, and 10% of dry matter on nutrient degradation, ruminal fermentation, methane inhibition, and microbial community structure in in vitro rumen fermentation. The freeze-dried S. mcclurei at 2% supplementation significantly reduced CH 4 emissions by 18.85% and enhanced crude protein degradability. However, total VFA and acetate concentrations were lower in both treatments compared to the control. The microbial shifts included a decrease in Lachnospiraceae&#95;NK3A20&#95;group and Ruminococcus and an increase in Selenomonas , Succinivibrio , and Saccharofermentans , promoting propionate production. Additionally, a significant reduction in Methanomicrobium was observed, indicating direct methane mitigation. Freeze-dried S. mcclurei at a 2% supplementation level shows potential as an effective methane mitigation strategy with minimal impact on rumen fermentation, supported by detailed insights into microbial community changes.

Background: The choice of unicompartmental knee arthroplasty (UKA) vs. total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA., Methods: PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards., Results: Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P <0.00001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P = 0.02), less pain (MD: 0.75; 95% CI: 0.43-1.06; P <0.00001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P = 0.01) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P = 0.0002) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction., Conclusions: In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Knee osteoarthritis (KOA) is a common degenerative joint disease characterized by cartilage degradation, inflammation, and pain. Traditional Chinese Medicine, including JDJM (a herbal formula derived from the renowned Du Huo Ji Sheng Tang), has been used to alleviate symptoms of KOA, but its underlying mechanisms remain unclear., Objective: This study aims to elucidate the potential therapeutic mechanisms of JDJM in treating KOA through network pharmacology, weighted gene co-expression network analysis (WGCNA), molecular docking, and experimental validation in animal models., Methods: The active compounds of JDJM were identified through TCMSP database searches, and their potential targets were predicted using network pharmacology. WGCNA was employed to identify key modules and hub genes associated with KOA. Molecular docking was performed to assess the binding affinities of key compounds to critical inflammatory targets. Molecular dynamics (MD) simulations were used to evaluate the stability of the protein-ligand complexes. An experimental KOA model in rabbits was used to validate the therapeutic effects of JDJM. Histopathological examinations and inflammatory marker analyses were conducted to confirm the findings., Results: Network pharmacology and WGCNA analyses identified 21 key targets and pathways potentially involved in the therapeutic effects of JDJM. Molecular docking results showed that Glyasperin C had the highest docking scores with EGF and IL-1β, followed by Stigmasterol with IL-6, Myricanone with INS, and Sesamin with VEGFA. MD simulations confirmed the stability of these protein-ligand complexes, indicating strong and stable interactions. In the rabbit KOA model, JDJM treatment significantly improved knee joint morphology and reduced the levels of inflammatory markers, such as IL-6 and TNF-α. Histopathological analysis revealed reduced cartilage degradation and inflammation in the JDJM-treated group compared to controls., Conclusion: JDJM exhibits promising anti-inflammatory and cartilage-protective effects, making it a potential therapeutic option for KOA patients. Further experimental and clinical studies are warranted to confirm these findings and translate them into clinical practice.

Acute cutaneous lupus erythematosus (ACLE) is closely associated with systemic symptoms in systemic lupus erythematosus (SLE). This study aimed to identify potential biomarkers for ACLE and explore their association with SLE to enable early prediction of ACLE and identify potential treatment targets for the future. In total, 185 SLE-diagnosed patients were enrolled and categorized into two groups: those with ACLE and those without cutaneous involvement. After conducting logistic regression analysis of the differentiating factors, we concluded that tumor necrosis factor-alpha (TNF-α) is an independent risk factor for ACLE. Analysis of the receiver operating characteristic revealed an area under the curve of 0.716 for TNF-α. Additionally, both TNF-α and ACLE are positively correlated with disease activity. TNF-α shows promise as a biomarker for ACLE, and in SLE patients, ACLE may serve as a clear indicator of moderate-to-severe disease activity., (© 2024 Japanese Dermatological Association.)

The entomopathogenic fungus Beauveria bassiana provides an eco-friendly substitute to chemical insecticides for mosquito control. Nevertheless, its widespread application has been hindered by its comparatively slow efficacy in eliminating mosquitoes. To augment the potency of B. bassiana against Aedes mosquitoes, a novel recombinant strain, Bb -Cyt1Aa, was developed by incorporating the Bacillus thuringiensis toxin gene Cyt1Aa into B. bassiana . The virulence of Bb -Cyt1Aa was evaluated against Aedes aegypti and Aedes albopictus using insect bioassays. Compared to the wild-type (WT) strain, the median lethal time (LT 50 ) for A. aegypti larvae infected with Bb -Cyt1Aa decreased by 33.3% at a concentration of 1 × 10 8 conidia/mL and by 22.2% at 1 × 10 7 conidia/mL. The LT 50 for A. aegypti adults infected with Bb -Cyt1Aa through conidia ingestion was reduced by 37.5% at 1 × 10 8 conidia/mL and by 33.3% at 1 × 10 7 conidia/mL. Likewise, the LT 50 for A. aegypti adults infected with Bb -Cyt1Aa through cuticle contact decreased by 33.3% and 30.8% at the same concentrations, respectively. Furthermore, the Bb -Cyt1Aa strain also demonstrated increased toxicity against both larval and adult A. albopictus , when compared to the WT strain. In conclusion, our study demonstrated that the expression of B. thuringiensis toxin Cyt1Aa in B. bassiana enhanced its virulence against Aedes mosquitoes. This suggests that B. bassiana expressing Cyt1Aa has potential value for use in mosquito control., Importance: Beauveria bassiana is a naturally occurring fungus that can be utilized as a bioinsecticide against mosquitoes. Cyt1Aa is a delta-endotoxin protein produced by Bacillus thuringiensis that exhibits specific and potent insecticidal activity against mosquitoes. In our study, the expression of this toxin Cyt1Aa in B. bassiana enhances the virulence of B. bassiana against Aedes aegypti and Aedes albopictus , thereby increasing their effectiveness in killing mosquitoes. This novel strain can be used alongside chemical insecticides to reduce dependence on harmful chemicals, thereby minimizing negative impacts on the environment and human health. Additionally, the potential resistance of B. bassiana against mosquitoes in the future could be overcome by acquiring novel combinations of exogenous toxin genes. The presence of B. bassiana that expresses Cyt1Aa is of significant importance in mosquito control as it enhances genetic diversity, creates novel virulent strains, and contributes to the development of safer and more sustainable methods of mosquito control., Competing Interests: The authors declare no conflict of interest.

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., (© 2024 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Reduced kidney AMPK activity is associated with nutrient stress-induced chronic kidney disease (CKD) in male mice. In contrast, female mice resist nutrient stress-induced CKD. The role of kidney AMPK in sex-related organ protection against nutrient stress and metabolite changes was evaluated in diabetic kidney tubule-specific AMPKγ2KO (KTAMPKγ2ΚΟ) male and female mice. In wild-type (WT) males, diabetes increased albuminuria, urinary kidney injury molecule-1, hypertension, kidney p70S6K phosphorylation, and kidney matrix accumulation; these features were not exacerbated with KTAMPKγ2ΚΟ. Whereas WT females had protection against diabetes-induced kidney injury, KTAMPKγ2ΚΟ led to loss of female protection against kidney disease. The hormone 17β-estradiol ameliorated high glucose-induced AMPK inactivation, p70S6K phosphorylation, and matrix protein accumulation in kidney tubule cells. The mechanism for female protection against diabetes-induced kidney injury is likely via an estrogen-AMPK pathway, as inhibition of AMPK led to loss of estrogen protection to glucose-induced mTORC1 activation and matrix production. RNA sequencing and metabolomic analysis identified a decrease in the degradation pathway of phenylalanine and tyrosine resulting in increased urinary phenylalanine and tyrosine levels in females. The metabolite levels correlated with loss of female protection. The findings provide new insights to explain evolutionary advantages to females during states of nutrient challenges., (© 2024 by the American Diabetes Association.)

Emerging neural morphological vision sensors inspired by biological systems that integrate image perception, memory, and information computing are expected to transform the landscape of machine vision and artificial intelligence. However, stable and reconfigurable light-induced synaptic behavior always relies on independent gateport modulation. Despite its potential, the limitations of uncontrollable defects and ionic characteristics have led to simpler, smaller, and more integration-friendly two-terminal devices being used as sidelines. In this work, the synergy between ion migration barriers and readout voltage is proven to be the key to realizing stable, reconfigurable, and precisely controllable postsynaptic current in two-terminal devices. Following the same mechanism, optical and electrical signal synchronous triggering is proposed to serve as a preprocessing method to achieve a recognition accuracy of 96.5%. Impressively, the gradual ion accumulation during the training process induces photocurrent evolution, serving as a reference for the dynamic learning rate and boosting accuracy to 97.8% in just 10 epochs. The PSC modulation potential under short optical pulse of 20 ns is also revealed. This optoelectronic device with perception, memory, and computation capabilities can promote the development of new devices for future photonic neural morphological circuits and artificial vision., (© 2024 Wiley‐VCH GmbH.)

The axon initial segment (AIS) constitutes not only the site of action potential initiation, but also a hub for activity-dependent modulation of output generation. Recent studies shedding light on AIS function used predominantly post-hoc approaches since no robust murine in vivo live reporters exist. Here, we introduce a reporter line in which the AIS is intrinsically labeled by an ankyrin-G-GFP fusion protein activated by Cre recombinase, tagging the native Ank3 gene. Using confocal, superresolution, and two-photon microscopy as well as whole-cell patch-clamp recordings in vitro , ex vivo , and in vivo , we confirm that the subcellular scaffold of the AIS and electrophysiological parameters of labeled cells remain unchanged. We further uncover rapid AIS remodeling following increased network activity in this model system, as well as highly reproducible in vivo labeling of AIS over weeks. This novel reporter line allows longitudinal studies of AIS modulation and plasticity in vivo in real-time and thus provides a unique approach to study subcellular plasticity in a broad range of applications., Competing Interests: Conflict of interest The authors declare that they have no competing interests.

Background: Ice and snow sports, which are inherently high risk due to their physically demanding nature, pose significant challenges in terms of participant safety. These activities increase the likelihood of injuries, largely due to reduced bodily agility and responsiveness in cold, often unpredictable winter environments. The critical need for effective injury prevention in these sports is emphasized by the considerable impact injuries have on the health of participants, alongside the economic and social costs associated with medical and rehabilitative care. In the context of ice and snow sports environments, applying the E principles of injury prevention to evaluate intervention measures can guide the implementation of future sports safety and other health promotion intervention measures in this field. When well executed, this approach can substantially reduce both the frequency and severity of injuries, thereby significantly enhancing the safety and long-term viability of these challenging sports., Objective: The objective of this study was to rigorously assess and statistically substantiate the efficacy of diverse injury prevention strategies in ice and snow sports, aiming to bolster future safety measures with solid empirical evidence., Design: Systematic review and meta-analysis., Methods: The overarching aim of this research was to meticulously aggregate and scrutinize a broad spectrum of scholarly literature, focusing on the quantifiable efficacy of diverse, multicomponent intervention strategies in mitigating the incidence of injuries within the realm of ice and snow sports. This endeavour entailed an exhaustive extraction of data from esteemed academic databases, encompassing publications up to September 30, 2023. In pursuit of methodological excellence and analytical rigor, the study employed advanced bias assessment methodologies, notably the AMSTAR 2 and GRADE approaches, alongside sophisticated random-effects statistical modelling. This comprehensive approach was designed to ensure the utmost validity, reliability, and scholarly integrity of the study's findings., Results: Fifteen papers, including 9 randomized controlled trials, 3 case‒control studies, and 3 cohort studies with 26,123 participants and 4,382 injuries, were analysed. The findings showed a significant reduction in injury rates through various interventions: overall injury prevention (RR = 0.50, 95% CI 0.42-0.63), educational training (RR = 0.50, 95% CI 0.34-0.73), educational videos (RR = 0.53, 95% CI 0.34-0.81), protective equipment (RR = 0.64, 95% CI 0.46-0.87), and policy changes (RR = 0.28, 95% CI 0.16-0.49). Subgroup analysis revealed potential heterogeneity in compliance (p = 0.347). Compared to controls, multicomponent interventions effectively reduced injury rates., Conclusion: This systematic review and meta-analysis demonstrated that multicomponent interventions significantly prevent injuries in ice and snow sports. By applying the E principles of injury prevention and constructing a framework for practical injury prevention research in ice and snow sports, we can gradually shift towards a systemic paradigm for a better understanding of the development and prevention of sports injuries. Moreover, sports injury prevention is a complex and dynamic process. Therefore, high-quality experiments in different scenarios are needed in future research to provide more reliable evidence, offer valuable and relevant prevention information for practitioners and participants, and help formulate more effective preventive measures in practice., (© 2024. The Author(s).)

Polymyxin is used as a last resort antibiotics for infections caused by multi-drug resistant (MDR) Gram-negative bacteria and is often combined with other antibiotics to improve clinical effectiveness. However, the synergism of colistin and other antibiotics remains obscure. Here, we revealed a notable synergy between colistin and flavomycin, which was traditionally used as an animal growth promoter and has limited activity against Gram-negative bacteria, using checkerboard assay and time-kill curve analyses. The importance of membrane penetration induced by colistin was assessed by examining the intracellular accumulation of flavomycin and its antimicrobial impact on Escherichia coli ( E. coli ) strains with truncated lipopolysaccharides. Besides, a mutation in the flavomycin binding site was created to confirm its role in the observed synergy. This synergy is manifested as an augmented penetration of the E. coli outer membrane by colistin, leading to increased intracellular accumulation of flavomycin and enhanced cell killing thereafter. The observed synergy was dependent on the antimicrobial activity of flavomycin, as mutation of its binding site abolished the synergy. In vivo studies confirmed the efficacy of colistin combined with flavomycin against MDR E. coli infections. This study is the first to demonstrate the synergistic effect between colistin and flavomycin, shedding light on their respective roles in this synergism. Therefore, we propose flavomycin as an adjuvant to enhance the potency of colistin against MDR Gram-negative bacteria., Importance: Colistin is a critical antibiotic in combating multi-drug resistant Gram-negative bacteria, but the emergence of mobilized colistin resistance (mcr) undermines its effectiveness. Previous studies have found that colistin can synergy with various drugs; however, its exact mechanisms with hydrophobic drugs are still unrevealed. Generally, the membrane destruction of colistin is thought to be the essential trigger for its interactions with its partner drugs. Here, we use clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) for specifically mutating the binding site of one hydrophobic drug (flavomycin) and show that antimicrobial activity of flavomycin is critical for the synergy. Our results first give the evidence that the synergy is set off by colistin's membrane destruction and operated the final antimicrobial function by its partner drugs., Competing Interests: The authors declare no conflict of interest.

The reform of China's "three subsidies" has shifted the method of subsidization from payment based on the contracted area to payment based on the actual operational area. Within this context, studying the income-generating impact of the "three subsidies" holds significant practical relevance. Using data from the 2018 China Labor-force Dynamic Survey, this paper employs basic estimation, mediating effect, and moderating effect models to analyze the heterogeneity of agricultural subsidies' impact on rural household income, the mediating effect of agricultural mechanization, and the moderating effect of operation scale. Our findings indicate that agricultural subsidies, known as the "three subsidies", have increased total rural household income and agricultural income while decreasing wage income. However, they have shown no significant impact on business income. Notably, agricultural subsidies have significantly elevated the income of food-producing households, with agricultural mechanization partially mediating this effect. Operation scale positively moderates the impact of agricultural subsidies on rural household income and agricultural mechanization. Heterogeneity analysis indicates that agricultural subsidies have a more significant impact on rural household income among agricultural producers in the eastern region., (© 2024. The Author(s).)

In this study, a new type of gold nano-bipyramids@CuZn bimetallic organic framework (AuNBPs@CuZn MOF) nanozyme with high peroxidase (POD)-like activity and surface enhanced Raman scattering (SERS) activity was constructed with a special core-shell structure, which can catalyze the oxidation of TMB (colourless and Raman-inactive) into ox-TMB (blue and Raman-active). An AuNBPs@CuZn MOF-enabling universal SERS and colorimetric dual-model bioassay was thus developed for biomolecules with excellent performance, and has promising application prospects in the biosensing fields.

Background: Zinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown., Methods: Through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration., Results: It was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments., Conclusions: Anoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs., (© 2024. The Author(s).)

Light detection and ranging (LiDAR) is indispensable in applications such as unmanned aerial vehicles, autonomous driving, and biomimetic robots. However, the precision and available distance of LiDAR are constrained by the speed and sensitivity of the photodetector, necessitating the use of expensive and energy-consuming avalanche diodes. To address these challenges, in this study, a pyroelectricity-based acceleration strategy with 2D-(graded 3D) perovskite heterojunction is proposed to achieve a record high speed (27.7 ns with an active area of 9 mm 2 , and 176 ps with an active area of 0.2 mm 2 ) and high responsivity (0.65 A W -1 ) at zero bias. This success is attributed to the unique mechanism where the electrons from the pyroelectric effect at the Cl-rich 2D/3D interface directly recombine with excess holes during light-dark transitions, breaking speed limitations related to carrier mobility and capacitive effect. Furthermore, the introduced pyroelectric effect significantly enhances the photoresponse, resulting in a self-powered external quantum efficiency exceeding 100%. The study also demonstrates precise position detection at the centimeter level. In conclusion, this research presents a pioneering approach for developing high-speed photodiodes with exceptional sensitivity, mitigating energy and cost concerns in LiDAR applications., (© 2024 Wiley‐VCH GmbH.)

Background: Extrathyroid implantation or dissemination of thyroid tissue secondary to a thyroid procedure is rare. Most of these belonged to thyroid carcinoma with metastatic potential and uncommon for benign pathologies., Methods: We report the case of a 31-year-old female who was identified to have multiple subcutaneous implantation of thyroid tissue 5 years after transoral endoscopic thyroidectomy vestibular approach. A comprehensive literature search on implantation of thyroid tissue secondary to thyroid procedures was performed., Results: Accidental tearing of the capsule during previous surgery may lead to the subcutaneous implantation. Through literature review, a total 29 articles with 47 patients were identified. 33.3% were benign lesions, and implantation was mostly secondary to fine needle aspiration biopsy (46.5%)., Conclusions: Subcutaneous or port site implantation after endoscopic thyroid surgery may occur in benign thyroid pathologies and therefore, oncologic principles must be strictly followed during surgery regardless of its histopathological nature., (© 2024 Wiley Periodicals LLC.)

Low-toxicity tin halide perovskites with excellent optoelectronic properties are promising candidates for photodetection. However, tin halide perovskite photodetectors have suffered from high dark current owing to uncontrollable Sn 2+ oxidation. Here, 2-cyanoethan-1-aminium iodide (CNI) is introduced in CH(NH 2 ) 2 SnI 3 (FASnI 3 ) perovskite films to inhibit Sn 2+ oxidation by the strong coordination interaction between the cyano group (C≡N) and Sn 2+ . Consequently, FASnI 3 -CNI films exhibit reduced nonradiative recombination and lower trap density. The self-powered photodetector based on FASnI 3 -CNI exhibits low dark current (1.04 × 10 -9 A cm -2 ), high detectivity (2.2 × 10 13 Jones at 785 nm), fast response speed (2.62 µs), and good stability. Mechanism studies show the increase in the activation energy required for thermal emission and generated carriers, leading to a lower dark current in the FASnI 3 -CNI photodetector. In addition, flexible photodetectors based on FASnI 3 -CNI, exhibiting high detectivity and fast response speed, are employed in wearable electronics to monitor the human heart rate under weak light and zero bias conditions. Finally, the FASnI 3 -CNI perovskite photodetectors are integrated with a 32 × 32 thin-film transistor backplane, capable of ultraweak light (170 nW cm -2 ) real-time imaging with high contrast, and zero power consumption, demonstrating the great potential for image sensor applications., (© 2024 Wiley‐VCH GmbH.)

The aim of this study was to assess the impact of varying proportions (5-20%) of hydroponic wheat sprouts in the diet of growing four-month-old Hu ewes on their productive performance, metabolic profiles, rumen fermentation, and alterations in microflora. Compared with the control group (CON), the optimum final weight of ewes has been presented in the group of substitution 15% (S15) of the basal diet with hydroponic wheat sprouts. Furthermore, 1-30 d the average daily gain (ADG), 31-60 d ADG, and average feed intake were both significantly improved in S15 compared with CON ( p < 0.05). Feeding hydroponic wheat sprouts can significantly increase high-density lipoprotein and interleukin-2 ( p < 0.05) accompanied by the numerical increase of the content of interferon-γ, suggesting its positive effect on ewes' health and immune systems. In this process, it is noteworthy that feeding hydroponic wheat sprouts results in an increase in relative abundance of Olsenella , Limosilactobacillus , Shuttleworthia , and Prevotella &#95;7, and a decrease in relative abundance of Succinimonas , Pseudobutyrivibrio , and Anaerovibrio in the rumen of growing ewes. It implies that the response of rumen microflora adapted to the change of dietary ingredients, as well as the relationship between rumen microflora changes and the improvement of productive performance and immune system in growing ewes. Considering the usage cost and application effect, S15 of the basal diet with hydroponic wheat sprouts could be the appropriate application solution for growing ewes.

Background: Neurofibromatosis type 1 is a genetic disease that affects multiple organs and systems, leading to various clinical manifestations. In Neurofibromatosis type 1, rare intrathoracic meningoceles often occur alongside bone dysplasia. These meningoceles contain cerebrospinal fluid and can be mistakenly diagnosed as 'pleural effusion'., Case Presentation: In this case report, we mistakenly identified 'cerebrospinal fluid' as 'pleural effusion' and proceeded with drainage. This error posed significant risks to the patient and holds valuable implications for the future diagnosis and treatment of similar patients., Conclusions: In patients with Neurofibromatosis type 1 complicated by spinal deformity, there is a high incidence of intrathoracic meningoceles. Treatment strategies may differ based on the specific features of the lesions, and collaboration among multiple disciplines can significantly improve patient outcomes., (© 2024. The Author(s).)

Artificial insemination (AI) with liquid-preserved semen has recently become common in pig breeding. The semen doses are produced in a centralized manner at the boar stud and then subsequently distributed and transported to sow farms. However, vibration emissions during transportation by logistic vehicles may adversely affect the quality of boar sperm. Therefore, this study aimed to explore the impact of vibration-induced emissions on sperm quality and function under simulated transportation conditions. Each time, ejaculates from all 15 boars were collected and then pooled together to minimize individual variations, and the sample was split using an extender for dilution. Different rotational speeds (0 rpm, 80 rpm, 140 rpm, 200 rpm) were utilized to simulate varying intensities of vibration exposure using an orbital shaker, considering different transportation times (0 h, 3 h, and 6 h). Subsequently, evaluations were conducted regarding sperm motility, plasma membrane integrity, acrosome integrity, mitochondrial function, adenosine triphosphate (ATP) levels, mitochondrial reactive oxygen species (ROS) levels, pH, glycolytic pathway enzyme activities, and capacitation following exposure to vibration emissions. Both vibration time and intensity impact sperm motility, plasma membrane integrity, and acrosomal integrity. Vibration exposure significantly reduced sperm ATP levels, mitochondrial membrane potential, and the levels of mitochondria-encoded proteins (MT-ND1, MT-ND6) ( p < 0.05). After vibration emission treatment, the pH value and mitochondrial ROS levels significantly increased ( p < 0.05). Inhibition of sperm glycolysis was observed, with reduced activities of hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH), along with decreased lactate levels ( p < 0.05). Additionally, sperm tyrosine phosphorylation levels were significantly reduced by vibration emissions compared to the control group ( p < 0.05). After the vibration emission treatment, the number of sperm bound to each square millimeter of oviduct explants decreased significantly compared to the control group ( p < 0.05). Similarly, compared to the control group, using semen subjected to vibration stress for AI results in significantly reduced pregnancy rates, total born litter size, live-born litter size, and healthy born litter size ( p < 0.05).

An excellent compatible and cost-effective dynamic kinetic resolution (DKR) protocol has been developed by combining a novel immobilized oxovanadium racemization catalyst onto cheap diatomite (V-D) with an immobilized lipase LA resolution catalyst onto a macroporous resin (LA-MR). V-D was prepared via grinding immobilization, which may become a promising alternative for the immobilization of metals, especially precious metals due to its low cost, high efficiency, easy separation, and large reaction interface. The DKR afforded high yield (96.1%), e.e. (98.67%), and Sel (98.28%) under optimal conditions established using response surface methodology as follows: the amount of V-D 10.83 mg, reaction time 51.2 h, and temperature 48.1 °C, respectively, indicating that all the reactions in the DKR were coordinated very well. The DKR protocol was also found to have high stability up to six reuses. V-D exhibited excellent compatibility with LA-MR because the lipase immobilized onto MR did not physically contact with the vanadium species immobilized onto diatomite, thus avoiding inactivation. Considering that lipase, oxovanadium, diatomite, and MR used are relatively inexpensive, and the adsorption or grinding immobilization is simple, the LA-V-MD DKR by coupling LA-MR with V-D is a cost-effective and promising protocol for chiral secondary alcohols.

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., (© 2024. The Author(s).)

Reproduction in goats is a highly complex and dynamic process of life regulation, involving coordinated regulation from various aspects such as central nervous system regulation, reproductive system development, oocyte maturation, and fertilized egg development. In recent years, researchers have identified numerous genes associated with goat reproductive performance through high-throughput sequencing, single-cell sequencing, gene knockout, and other techniques. However, there is still an urgent need to explore marker genes related to goat reproductive performance. In this study, a single-cell RNA sequencing dataset of oocytes (GSE136005) was obtained from the Gene Expression Omnibus (GEO) database. Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to identify modules highly correlated with goat litter size. Through gene function enrichment analysis, it was found that genes within the modules were mainly enriched in adhesive junctions, cell cycle, and other signaling pathways. Additionally, the top 30 hub genes with the highest connectivity in WGCNA were identified. Subsequently, using Protein-Protein Interaction (PPI) network analysis, the top 30 genes with the highest connectivity within the modules were identified. The intersection of hub genes, key genes in the PPI network, and differentially expressed genes (DEGs) led to the identification of the RPL4 gene as a key marker gene associated with reproductive capacity in goat oocytes. Overall, our study reveals that the RPL4 gene in oocytes holds promise as a biological marker for assessing goat litter size, deepening our understanding of the regulatory mechanisms underlying goat reproductive performance.

Introduction: Desmoid 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., Methods: We 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., Results: In 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%., Conclusion: Anlotinib 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., 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 © 2024 Xie, Huang, Gong, Wang, Li, Lu, Luo, Min, Zhou and Tu.)

Background: Retroperitoneal liposarcoma (RPLS) is known for its propensity for local recurrence and short survival time. We aimed to identify a credible and specific prognostic biomarker for RPLS., Methods: Cases from The Cancer Genome Atlas (TCGA) sarcoma dataset were included as the training group. Co-expression modules were constructed using weighted gene co-expression network analysis (WGCNA) to explore associations between modules and survival. Survival analysis of hub genes was performed using the Kaplan-Meier method. In addition, independent external validation was performed on a cohort of 135 Chinese RPLS patients from the REtroperitoneal SArcoma Registry (RESAR) study (NCT03838718)., Results: A total of 19 co-expression modules were constructed based on the expression levels of 26,497 RNAs in the TCGA cohort. Among these modules, the green module exhibited a positive correlation with overall survival (OS, p = 0.10) and disease-free survival (DFS, p = 0.06). Gene set enrichment analysis showed that the green module was associated with endocytosis and soft-tissue sarcomas. Survival analysis demonstrated that NINJ1, a hub gene within the green module, was positively associated with OS (p = 0.019) in the TCGA cohort. Moreover, in the validation cohort, patients with higher NINJ1 expression levels displayed a higher probability of survival for both OS (p = 0.023) and DFS (p = 0.012). Multivariable Cox analysis further confirmed the independent prognostic significance of NINJ1., Conclusions: We here provide a foundation for the establishment of a consensus prognostic biomarker for RPLS, which should not only facilitate medical treatment but also guide the development of novel targeted drugs., (© 2024. The Author(s).)

Background: Ischemic stroke (IS) is a neurological disease with significant disability and mortality. MicroRNAs were proven to be associated with cerebral ischemia. Previous studies have demonstrated miR-122 downregulation in both animal models of IS and the blood of IS patients. Nonetheless, the role and mechanism of miR-122-5p in IS remain unclear., Methods: We established primary human and mouse astrocytes, along with HT22 mouse hippocampal neuronal cells, through oxygen-glucose deprivation/reoxygenation (OGD/R) treatment. To assess the impact of miR-122, we employed CCK8 assays, flow cytometry, RT-qPCR, western blotting, and ELISA to evaluate cell viability, apoptosis, reactive oxygen species (ROS) generation, and cytokine expression. A dual-luciferase reporter gene assay was employed to investigate the interaction between miR-122 and sPLA2-IIA., Results: Overexpression of miR-122 resulted in decreased apoptosis, reduced cleaved caspase-3 expression, and increased cell viability in astrocytes and HT22 cells subjected to OGD/R. RT-qPCR and ELISA analyses demonstrated a decrease in mRNA and cytokine levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in both astrocytes and HT22 cells following miR-122 overexpression. Moreover, miR-122 overexpression reversed OGD/R-induced ROS levels and 8-OHdG formation in astrocytes. Additionally, miR-122 overexpression decreased the mRNA and protein expression of inducible nitric oxide synthase (iNOS). Furthermore, we found that miR-122 attaches to the 3'-UTR of sPLA2-IIA, thereby downregulate its expression., Conclusion: Our study demonstrates that miR-122-mediated inhibition of sPLA2-IIA attenuates OGD/R-induced neuronal injury by suppressing apoptosis, alleviating post-ischemic inflammation, and reducing ROS production. Thus, the miR-122/sPLA2-IIA axis may represent a promising target for IS treatment., 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 © 2024 Yu, Li, Chen, Zhan, Zhu, Min, Liu and Lv.)

Background: Helicobacter pylori (H. pylori) is the predominant etiological agent of gastritis and disrupts the integrity of the gastric mucosal barrier through various pathogenic mechanisms. After H. pylori invades the gastric mucosa, it interacts with immune cells in the lamina propria. Macrophages are central players in the inflammatory response, and H. pylori stimulates them to secrete a variety of inflammatory factors, leading to the chronic damage of the gastric mucosa. Therefore, the study aims to explore the mechanism of gastric mucosal injury caused by inflammatory factors secreted by macrophages, which may provide a new mechanism for the development of H. pylori-related gastritis., Methods: The expression and secretion of CCL3 from H. pylori infected macrophages were detected by RT-qPCR, Western blot and ELISA. The effect of H. pylori-infected macrophage culture medium and CCL3 on gastric epithelial cells tight junctions were analyzed by Western blot, immunofluorescence and transepithelial electrical resistance. EdU and apoptotic flow cytometry assays were used to detect cell proliferation and apoptosis levels. Dual-luciferase reporter assays and chromatin immunoprecipitation assays were used to study CCL3 transcription factors. Finally, gastric mucosal tissue inflammation and CCL3 expression were analyzed by hematoxylin and eosin staining and immunohistochemistry., Results: After H. pylori infection, CCL3 expressed and secreted from macrophages were increased. H. pylori-infected macrophage culture medium and CCL3 disrupted gastric epithelial cells tight junctions, while CCL3 neutralizing antibody and receptor inhibitor of CCL3 improved the disruption of tight junctions between cells. In addition, H. pylori-infected macrophage culture medium and CCL3 recombinant proteins stimulated P38 phosphorylation, and P38 phosphorylation inhibitor improved the disruption of tight junctions between cells. Besides, it was identified that STAT1 was a transcription factor of CCL3 and H. pylori stimulated macrophage to secret CCL3 through the JAK1-STAT1 pathway. Finally, after mice were injected with murine CCL3 recombinant protein, the gastric mucosal injury and inflammation were aggravated, and the phosphorylation level of P38 was increased., Conclusions: In summary, our findings demonstrate that H. pylori infection stimulates macrophages to secrete CCL3 via the JAK1-STAT1 pathway. Subsequently, CCL3 damages gastric epithelial tight junctions through the phosphorylation of P38. This may be a novel mechanism of gastric mucosal injury in H. pylori-associated gastritis., (© 2024. The Author(s).)

Purpose: The spinopelvic reconstruction poses significant challenges following total sacrectomy in patients with malignant or aggressive benign bone tumours encompassing the entire sacrum. In this study, we aim to assess the functional outcomes and complications of an integrated 3D-printed sacral endoprostheses featuring a self-stabilizing design, eliminating the requirement for supplemental fixation., Methods: We retrospectively analyzed patients with sacral tumours who underwent total sacrectomy followed by reconstruction with 3D-printed self-stabilizing endoprosthesis. Clinically, we evaluated functional outcomes using the 1993 version of the musculoskeletal tumour society (MSTS-93) score. Perioperative and postoperative complications were also documented., Results: 10 patients met final inclusion criteria. The median age was 49 years (range, 31-64 years). The median follow-up time was 26.5 months (range, 15-47 months). Median postoperative functional MSTS-93 was 22.5 (range, 13-25). The median operation time was 399.5 min (305-576 min), and the median intraoperative blood loss was and 3200 ml (2400-7800 ml). Complications include wound dehiscence in one patient, bowel, bladder, and sexual dysfunction in four patients, cerebrospinal fluid leak in one patient, and tumour recurrence in one patient. There were no mechanical complications related to the endoprosthesis at the last follow-up., Conclusion: The utilization of 3D-printed self-stabilizing endoprosthesis proved to be a viable approach, yielding satisfactory short-term outcomes in patients undergoing total sacral reconstruction without supplemental fixation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2024. The Author(s).)

Objective: The present study aimed to investigate the effect of β-nicotinamide mononucleotide (NMN) supplementation on ram sperm quality during storage at 4°C in vitro., Methods: Tris-citric acid-glucose solution containing different doses of NMN (0, 30, 60, 90, and 120 μM) was used to dilute semen collected from rams and it was stored at 4°C. Sperm motility, plasma membrane integrity as well as acrosome integrity were evaluated at 0, 24, and 48 h time points after storage at 4°C. In addition, sperm mitochondrial activity, lipid peroxidation (LPO), malondialdehyde (MDA) content, reactive oxygen species (ROS) content, glutathione (GSH) content, superoxide dismutase (SOD) activity, and apoptosis were measured at 48 h time point after storage at 4°C., Results: Results demonstrate that the values obtained for sperm motility, acrosome integrity, and plasma membrane integrity in the NMN treatments were significantly higher than control (p<0.05). The addition of 60 μM NMN significantly improved ram sperm mitochondrial activity and reduced LPO, MDA content, and ROS content compared to control (p<0.05). Interestingly, sperm GSH content and SOD activity for the 60 μM NMN treatment were much higher than those observed for control. NMN treatment also decreased the level of Cleaved-Caspase 3, Cleaved-Caspase 9, and Bax while increasing Bcl-2 level in sperm at 48 h time point after storage at 4°C., Conclusion: Ram sperm quality can be maintained during storage at 4°C with the addition of NMN at 60 μM to the semen extender. NMN also reduces oxidative stress and apoptosis. Overall, these findings suggest that NMN is efficient in improving the viability of ram sperm during storage at 4°C in vitro.

Dirac and Weyl semimetals are a central topic of contemporary condensed matter physics, and the discovery of new compounds with Dirac/Weyl electronic states is crucial to the advancement of topological materials and quantum technologies. Here we show a widely applicable strategy that uses high configuration entropy to engineer relativistic electronic states. We take the AMnSb 2 (A = Ba, Sr, Ca, Eu, and Yb) Dirac material family as an example and demonstrate that mixing of Ba, Sr, Ca, Eu and Yb at the A site generates the compound (Ba 0.38 Sr 0.14 Ca 0.16 Eu 0.16 Yb 0.16 )MnSb 2 (denoted as A 5 MnSb 2 ), giving access to a polar structure with a space group that is not present in any of the parent compounds. A 5 MnSb 2 is an entropy-stabilized phase that preserves its linear band dispersion despite considerable lattice disorder. Although both A 5 MnSb 2 and AMnSb 2 have quasi-two-dimensional crystal structures, the two-dimensional Dirac states in the pristine AMnSb 2 evolve into a highly anisotropic quasi-three-dimensional Dirac state triggered by local structure distortions in the high-entropy phase, which is revealed by Shubnikov-de Haas oscillations measurements., (© 2024. The Author(s).)

Introduction: To evaluate the effect of Embrella, a novel-designed colonoscopic distal attachment, on adenoma detection rate (ADR) and adenoma per colonoscopy (APC), compared with standard colonoscopy in routine practice., Methods: All consecutive participants who underwent routine colonoscopic examinations at 3 endoscopy centers in China were enrolled. Participants were randomly assigned in a 1:1 ratio to the Embrella-assisted colonoscopy (EAC) or standard colonoscopy (SC) groups. ADR, APC, inspection time, pain scores, and adverse events were recorded., Results: Overall, 1,179 participants were randomized into the EAC (n = 593) and SC groups (n = 586). EAC increased the overall ADR from 24.6% to 34.2% ( P < 0.001) and improved APC from 0.44 to 0.64 ( P = 0.002). Subgroup analyses indicated that EAC significantly improved ADR for adenomas < 10 mm (13.8% vs 8.5%, P = 0.004 for 5-9 mm and 27.0% vs 17.2%, P < 0.001 for < 5 mm), nonpedunculated adenomas (26.6% vs 18.8%, P < 0.001), and adenomas in the transverse (10.8% vs 6.1%, P = 0.004) and left colon (21.6% vs 13.7%, P < 0.001). APC in the subgroup analyses was consistent with ADR. The mean inspection time was shorter with EAC (6.52 vs 6.68 minutes, P = 0.046), with no significant impact on participants' pain scores ( P = 0.377). Moreover, no EAC-related adverse events occurred., Discussion: EAC significantly increased ADR and APC compared with SC, particularly for adenomas <10 mm, nonpedunculated adenomas, and adenomas in the transverse and left colon., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)