Conversion Total Hip Arthroplasty After Failed Pedicled Peri-Hip Bone Flap Grafting: The Chinese Experience.

BACKGROUND: This study investigated the perioperative outcomes of patients undergoing conversion total hip arthroplasty (THA) after failed peri-hip bone flap grafting (PBFG) and compared them with those patients undergoing primary THA for osteonecrosis of the femoral head (ONFH). METHODS: From January 2010 to December 2021, 163 Chinese patients (163 hips) were treated by conversion THA after failed PBFG (containing 94 patients who had pedicled vascularized iliac bone flap grafting and 69 patients who had pedicled vascularized greater trochanter bone flap grafting), and 178 Chinese patients were treated by primary THA. The preoperative baseline data and perioperative indicators in both groups were compared. RESULTS: In the conversion group, patients had significantly greater blood loss, a longer length of stay, and greater changes in serum hemoglobin than those in the primary THA group (P < 0.05). The operative room time, transfusion volume, calculated blood loss, changes in serum hematocrit, and increased superficial infection (P > 0.05) in the conversion group were greater compared with the primary cohort; however, the difference was not statistically significant. The mean postoperative Harris Hip Scoring System (HHS) of the PBFG group at the one-month follow-up was 81, and the control group had an 82 score. Importantly, subgroup analysis of the PBFG group indicated that there was no significant difference between patients who had prior pedicled vascularized iliac bone flap grafting and pedicled vascularized greater trochanter bone flap grafting (P > 0.05), except for the operative room time (P = 0.032). CONCLUSION: Hip-sparing surgery of ONFH did not make THA more difficult or lead to more peri-operative complications, but increased blood loss and extended hospital stay from a prior PBFG are still notable problems in clinical practice. Thus, it is necessary for surgeons to focus attention on the improvement of the preoperative condition and prepare for any specific intraoperative challenges.

Recent Functionalized Strategies of Metal-Organic Frameworks for Anode Protection of Aqueous Zinc-Ion Battery.

The inherent benefits of aqueous Zn-ion batteries (ZIBs), such as environmental friendliness, affordability, and high theoretical capacity, render them promising candidates for energy storage systems. Nevertheless, the Zn anodes of ZIBs encounter severe challenges, including dendrite formation, hydrogen evolution reaction, corrosion, and surface passivation. These would result in the infeasibility of ZIBs in practical situations. To this end, artificial interfaces with functionalized materials are crafted to protect the Zn anode. They have the capability to modulate the zinc ion flux in proximity to the electrode surface and shield it from aqueous electrolytes by leveraging either size effects or charge effects. Considering metal-organic frameworks (MOFs) with tunable pore size, chemical composition, and stable framework structures, they have emerged as effective materials for building artificial interfaces, prolonging the lifespan, and improving the unitization of Zn anode. In this review, the contributions of MOFs for protecting Zn anode, which mainly involves facilitating homogeneous nucleation, manipulating selective deposition, regulating ion and charge flux, accelerating Zn desolvation, and shielding against free water and anions are comprehensively summarized. Importantly, the future research trajectories of MOFs for the protection of the Zn anode are underscored, which may propose new perspectives on the practical Zn anode and endow the MOFs with high-value applications.

Stabilization of CsPbBr3 Nanowires Through SU-8 Encapsulation for the Fabrication of Bilayer Microswimmers with Magnetic and Fluorescence Properties.

All-inorganic cesium lead halide (CsPbX3, X = Cl, Br, I) perovskite nanocrystals have drawn great interest because of their excellent photophysical properties and potential applications. However, their poor stability in water greatly limited their use in applications that require stable structures. In this work, a facile approach to stabilize CsPbBr3 nanowires is developed by using SU-8 as a protection medium; thereby creating stable CsPbBr3/SU-8 microstructures. Through photolithography and layer-by-layer deposition, CsPbBr3/SU-8 is used to fabricate bilayer achiral microswimmers (BAMs), which consist of a top CsPbBr3/SU-8 layer and a bottom Fe3O4 magnetic layer. Compared to pure CsPbBr3 nanowires, the CsPbBr3/SU-8 shows long-term structural and fluorescence stability in water against ultrasonication treatment. Due to the magnetic layer, the motion of the microswimmers can be controlled precisely under a rotating magnetic field, allowing them to swim at low Reynolds number and tumble or roll on surfaces. Furthermore, CsPbBr3/SU-8 can be used to fabricate various types of planar microstructures with high throughput, high consistency, and fluorescence properties. This work provides a method for the stabilization of CsPbBr3 and demonstrates the potential to mass fabricate planar microstructures with various shapes, which can be used in different applications such as microrobotics.

Discovery of N'-benzyl-3-chloro-N-((1S,3R,4R)-3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)cyclohexyl)benzenesulfonamide as a novel selective KOR ligand.

The effective management of moderate to severe pain often relies on the use of analgesic agents. However, the widespread utility of these medications is hindered by the occurrence of several undesirable side effects. In light of this challenge, there is growing interest in the development of κ opioid receptor (KOR) agonists, which have shown promise in mitigating these adverse effects. In this study, leveraging the structural scaffold of compound D (our previous study), we embarked on the design, synthesis, and evaluation of a series of N'-benzyl-3-chloro-N- ((1S,3R,4R)-3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)cyclohexyl)benzenesulfonamide derivatives. These compounds were subjected to comprehensive in vitro and in vivo test. Through systematic structure-activity relationship (SAR) exploration, we successfully identified compound 23p (Ki(KOR):1.9 nM) as a highly selective KOR ligand of new chemotype. 23p showed high clearance in vitro PK test, and abdominal contraction test showed potent antinociceptive effect. 23p and its O-demethyl metabolite 25 were both found in the plasma of mouse, 25 also showed potent affinity toward KOR (Ki(KOR): 3.1 nM), both they contribute to the analgesic effect. Moreover, 23p exhibited potent antinociceptive activity in abdominal constriction test, which was effectively abolished by pre-treatment of nor-BNI, a selective KOR antagonist.

Hierarchical Supramolecular Aggregation of Molecular Nanoparticles for Granular Materials with Ultra High-Speed Impact-Resistance.

The high-speed impact-resistanct materials are of great significance while their development is hindered by the intrinsic tradeoff between mechanical strength and energy dissipation capability. Herein, the new chemical system of molecular granular material (MGM) is developed for the design of impact-resistant materials from the supramolecular complexation of sub-nm molecular clusters (MCs) and hyper-branched polyelectrolytes. Their hierarchical aggregation provides the origin of the decoupling of mechanical strengths and structural relaxation dynamics. The MCs' intrinsic fast dynamics afford excellent high-speed impact-resistance, up to 5600 s-1 impact in a typical split-Hopkinson pressure bar test while only tiny boundary cracks can be observed even under 7200 s-1 impact. The high loadings of MCs and their hierarchical aggregates provide high-density sacrificial bonding for the effective dissipation of the impact energy, enabling the protection of fragile devices from the direct impact of over 200 m s-1 bullet. Moreover, the MGMs can be conveniently processed into protective coatings or films with promising recyclability due to the supramolecular interaction feature. The research not only reveals the unique relaxation dynamics and mechanical properties of MGMs in comparison with polymers and colloids, but also develops new chemical systems for the fabrication of high-speed impact-resistant materials.

The role of testicular stiffness derived from shear wave elastography in the assessment of spermatogenesis in men with varicocele.

Background: Varicocele is a major correctable cause of male infertility. Shear wave elastography (SWE) represents a valuable approach for assessing spermatogenesis in infertile men; however, its application in infertile men with varicocele remains unreported in the literature to date. The objective of this study was to investigate the correlation between testicular stiffness and spermatogenesis in individuals with varicocele. Methods: A total of 568 participants with left-side varicocele and 475 age-matched healthy controls were enrolled. The mean, left, and right testicular volumes (Volume-mean, Volume-L, and Volume-R), the mean elastic modulus of bilateral, left, and right testes (Emean, Emean-L, and Emean-R); the maximum elastic modulus of bilateral, left, and right testes (Emax, Emax-L, and Emax-R); the minimum elastic modulus of bilateral, left, and right testes (Emin, Emin-L, and Emin-R) were calculated. Results: Receiver operating characteristic (ROC) curves for Volume-R and Emax were constructed to identify participants with sperm concentrations below 5 million/mL. The areas under the ROC curves (AUCs) were 0.801 and 0.775, respectively. Combining these 2 markers improved their diagnostic value with an AUC of 0.820 and sensitivity and specificity of 94.6% and 59.8% [95% confidence interval (CI): 0.772-0.867, P<0.01], respectively. A total of 69 participants underwent microsurgical varicocelectomy (including 42 cases with improved semen results and 27 without). The ROC curves of Emax-L and Volume-L were constructed for the differential diagnosis between the improved and unimproved groups; the AUCs were 0.723 and 0.855, respectively. Combining these 2 markers improved their diagnostic value with an AUC of 0.867 (95% CI: 0.772-0.961, P<0.01) and sensitivity and specificity of 81.5% and 81.0%, respectively. Conclusions: Our findings suggest that SWE can be used for varicocele to assess testicular parenchyma damage and Volume-L combined with Emax-L offers a more accurate method for predicting semen parameter improvement after microscopic subinguinal varicocelectomy in men with varicocele.

Testicular ultrasonic microvascular density in assessing spermatogenesis and predicting successful sperm retrieval.

Background: The relationship between microcirculatory disorders and testicular spermatogenesis is an area of ongoing interest among urologists. The objective of this prospective observational study was to investigate the correlation between testicular microcirculation and spermatogenesis, as well as the predictive value of ultrasonic microvascular density (UMVD) and ultrasonographic volume estimation (UVE) in successful sperm retrieval among men with non-obstructive azoospermia (NOA). Methods: Testicular UMVD derived from Angio PLUSTM Planwave Ultrasensitive Imaging (AP), UVE were obtained. Participants were divided into 4 groups (normozoospermia; asthenozoospermia, teratozoospermia, or asthenoteratozoospermia; oligozoospermia; NOA). Results: The study included a total of 875 participants. No significant difference was found in UMVD-mean between different semen groups (P>0.05). A total of 108 participants with NOA underwent microdissection testicular sperm extraction (micro-TESE). Participants with successful sperm retrieval (40 cases) showed significant differences in testicular UMVD and UVE compared to those with negative retrieval (68 cases) (P<0.01). We generated receiver operating characteristic (ROC) curves for UMVD and testicular UVE to differentiate participants with successful sperm retrieval from those without. The area under the curve (AUC) was 0.760 [95% confidence interval (CI): 0.658-0.849, P<0.01] for UMVD and 0.716 (95% CI: 0.609-0.822, P<0.01) for testicular UVE, respectively. The optimal cutoff value was determined based on the maximum Youden index. When UMVD was set at 28.50/cm2, its sensitivity and specificity were calculated as 57.5% and 85.3%, respectively. For testicular UVE, a cutoff value of 8.94 mL resulted in a sensitivity of 60.0% and specificity of 82.4%. Combining UMVD with testicular UVE improved diagnostic performance (AUC: 0.856, 95% CI: 0.772-0.929, P<0.01) with a sensitivity of 79.4% and specificity of 77.5%. Conclusions: The present study demonstrates the utility of AP as a predictive tool for successful sperm retrieval prior to micro-TESE. Furthermore, the combination of testicular UMVD and UVE provides a highly valuable diagnostic approach for predicting micro-TESE success and can be routinely implemented before the procedure. A testicular UMVD exceeding 28.50/cm2 and a testicular UVE larger than 8.94 mL strongly indicate favorable outcomes in terms of sperm retrieval.

Comprehensive cognition of yak (Bos grunniens) AIFM2 gene and its anti-ferroptosis role in bisphenol A-induced fetal fibroblast model.

Apoptosis-inducing factor mitochondrion-associated 2 (AIFM2) has been identified as a gene with anti-ferroptosis properties. To explore whether AIFM2 exerts anti-ferroptosis role in yaks (Bos grunniens), we cloned yak AIFM2 gene and analyzed its biological characteristics. The coding region of AIFM2 had 1122 bp and encoded 373 amino acids, which was conserved in mammals. Next, RT-qPCR results showed an extensive expression of AIMF2 in yak tissues. Furthermore, we isolated yak skin fibroblasts (YSFs) and established a bisphenol A (BPA)-induced ferroptosis model to further investigate the role of AIFM2. BPA elevated oxidative stress (reactive oxygen species, ROS) and lipid peroxidation (malondialdehyde, MDA and BODIPY), and reduced cell viability and antioxidant capacity (glutathione, GSH), with the severity depending on the dosage. Of note, a supplement of Ferrostatin-1 (Fer), an inhibitor of ferroptosis, restored the previously mentioned indicators. Subsequently, we constructed an AIFM2 overexpression vector and designed AIFM2 specific interfering siRNAs, which were transfected into YSFs. The results showed that overexpressing AIFM2 alleviated ferroptosis, characterizing by significant changes of cell viability, ROS, BODIPY, MDA and GSH. Meanwhile, interfering AIFM2 aggravated ferroptosis, demonstrating the critical anti-ferroptosis role of the yak AIFM2 gene. This study shed light on further exploring the molecular mechanism of AIFM2 in plateau adaptability.

Temporal variation of mercury and methyl mercury in water and accumulation by phytoplankton in the eutrophic estuary, northern Taiwan.

Three surveys were carried out to study the phytoplankton role in influencing the Hg distribution in a poorly eutrophic estuary by measuring the total Hg (THg) and methylHg (MeHg) concentrations in waters and four-size fractions of phytoplankton. The THg and MeHg concentrations in waters and phytoplankton varied markedly temporal during the three surveys. The total concentrations of THg and MeHg in the four-size fractions of phytoplankton ranged between 0.62 and 28.15 mg/kg and 0.022-4.411 mg/kg, respectively. The dominance of THg and MeHg phytoplankton concentrations differed from different size fractions and varied with the various surveys. The huge uptake of Hg by abundant phytoplankton decreased both Hg concentrations in waters and phytoplankton, which was attributed to the biomass dilution effect during the July survey. The Hg partition between water and phytoplankton provided substantial evidence to illustrate the huge uptake of Hg by the abundant phytoplankton.

Structure-Based Design and Discovery of a Potent and Cell-Active LC3A/B Covalent Inhibitor.

Autophagy is a highly conserved cellular homeostasis maintenance mechanism in eukaryotes. Microtubule-associated protein light chain 3 (LC3) plays a crucial role in autophagy. It has multiple pairs of protein-protein interactions (PPIs) with other proteins, and these PPIs have an effect on the regulation of autophagosome formation and the recruitment of autophagic substrates. In our previous work, a small molecule covalent inhibitor DC-LC3in-D5 which could inhibit LC3A/B PPIs was identified, but a detailed study of structure-activity relationships (SARs) was lacking. Herein, a new molecule LC3in-C42 was discovered utilizing the hybridization of advantageous fragments, whose potency (IC50 = 7.6 nM) had been greatly improved compared with that of DC-LC3in-D5. LC3in-C42 inhibits autophagy at the cellular level and its efficacy far exceeds that of DC-LC3in-D5. Thus far, LC3in-C42 stands as the most potent LC3A/B small molecule inhibitor. LC3in-C42 could serve as a powerful tool for LC3A/B protein and autophagy research.

A microbial metabolite inhibits the HIF-2α-ceramide pathway to mediate the beneficial effects of time-restricted feeding on MASH.

Time-restricted feeding (TRF) is a potent dietary intervention for improving metabolic diseases, including metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis (MASLD/MASH). However, the mechanism of this efficacy has remained elusive. Here, we show that TRF improves MASLD, which is associated with a significant enrichment of Ruminococcus torques (R. torques). Mechanistically, R. torques suppresses the intestinal HIF-2α-ceramide pathway via the production of 2-hydroxy-4-methylpentanoic acid (HMP). We identify rtMor as a 4-methyl-2-oxopentanoate reductase that synthesizes HMP in R. torques. Finally, we show that either the colonization of R. torques or oral HMP supplementation can ameliorate inflammation and fibrosis in a MASH mouse model. These findings identify R. torques and HMP as potential TRF mimetics for the treatment of metabolic disorders.

Inhibition of the p62-Nrf2-GPX4 Pathway Confers Sensitivity to Butachlor-Induced Splenic Macrophage Ferroptosis.

Butachlor is widely used in agriculture around the world and therefore poses environmental and public health hazards due to persistent and poor biodegradability. Ferroptosis is a type of iron-mediated cell death controlled by glutathione (GSH) and GPX4 inhibition. P62 is an essential autophagy adaptor that regulates Keap1 to activate nuclear factor erythroid 2-related factor 2 (Nrf2), which effectively suppresses lipid peroxidation, thereby relieving ferroptosis. Here, we found that butachlor caused changes in splenic macrophage structure, especially impaired mitochondrial morphology with disordered structure, which is suggestive of the occurrence of ferroptosis. This was further confirmed by the detection of iron metabolism, the GSH system, and lipid peroxidation. Mechanistically, butachlor suppressed the protein level of p62 and promoted Keap1-mediated degradation of Nrf2, which results in decreased GPX4 expression and accelerated splenic macrophage ferroptosis. These findings suggest that targeting the p62-Nrf2-GPX4 signaling axis may be a promising strategy for treating inflammatory diseases.

Exosome-shuttled miR-150-5p from LPS-preconditioned mesenchymal stem cells down-regulate PI3K/Akt/mTOR pathway via Irs1 to enhance M2 macrophage polarization and confer protection against sepsis.

Rationale: Sepsis is a life-threatening organ dysfunction and lack of effective measures in the current. Exosomes from mesenchymal stem cells (MSCs) reported to alleviate inflammation during sepsis, and the preconditioning of MSCs could enhance their paracrine potential. Therefore, this study investigated whether exosomes secreted by lipopolysaccharide (LPS)-pretreated MSCs exert superior antiseptic effects, and explored the underlying molecular mechanisms. Methods: Exosomes were isolated and characterized from the supernatants of MSCs. The therapeutic efficacy of normal exosomes (Exo) and LPS-pretreated exosomes (LPS-Exo) were evaluated in terms of survival rates, inflammatory response, and organ damage in an LPS-induced sepsis model. Macrophages were stimulated with LPS and treated with Exo or LPS-Exo to confirm the results of the in vivo studies, and to explain the potential mechanisms. Results: LPS-Exo were shown to inhibit aberrant pro-inflammatory cytokines, prevent organ damages, and improve survival rates of the septic mice to a greater extent than Exo. In vitro, LPS-Exo significantly promoted the M2 polarization of macrophages exposed to inflammation. miRNA sequencing and qRT-PCR analysis identified the remarkable expression of miR-150-5p in LPS-Exo compared to that in Exo, and exosomal miR-150-5p was transferred into recipient macrophages and mediated macrophage polarization. Further investigation demonstrated that miR-150-5p targets Irs1 in recipient macrophages and subsequently modulates macrophage plasticity by down-regulating the PI3K/Akt/mTOR pathway. Conclusion: The current findings highly suggest that exosomes derived from LPS pre-conditioned MSCs represent a promising cell-free therapeutic method and highlight miR-150-5p as a novel molecular target for regulating immune hyperactivation during sepsis.

Detection of minimal hepatic encephalopathy in patients with cirrhosis based on the Stroop-CN model (NCRCID-CHESS 2106): a prospective multicenter study.

Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop-CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop-CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child-Pugh grades and the Model for End-stage Liver Disease and Sodium (MELD-Na) scores in the test and validation cohort. The EuroQol 5-D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop-CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

Characterization of the complete chloroplast genome sequence of Bassia scoparia (L.) A. J. Scott 1978 (Amaranthaceae) and its phylogenetic analysis.

Bassia scoparia, an annual potherb belonging to the family Amaranthaceae, has been widely used in traditional Chinese and Japanese medicine for over 2000 years. Herein, we presented its complete chloroplast. The chloroplast genome sequence was 151,278 bp in length with a 36.6% content of GC. The genome showed the typical quadripartite structure, comprising a pair of inverted repeat (IR) regions (24,353 bp) separated by a large single-copy (LSC) region (84,067 bp) and a small single-copy (SSC) region (18,505 bp). This chloroplast genome harbored 133 predicted genes, including 88 protein-coding genes, 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The phylogenetic analysis indicated that B. scoparia was closely related to B. littorea. This newly sequenced chloroplast genome not only enhances our understanding of the genome of Bassia but also provides valuable insights for the evolutionary study of the family Amaranthaceae.

Design and experimental evaluation of a variable pesticide application control system for the air-assisted rubber tree powder sprayer.

BACKGROUND: In order to address the issues of uneven pesticide deposition and low pesticide utilization in rubber gardens caused by the traditional diffuse plant protection spraying method, this study focuses on the air-assisted powder sprayer and proposes a variable pesticide application control system. A variable pesticide application decision-making model integrating the leaf area index (LAI) was designed based on powdery mildew control standards and individual rubber tree information. According to the target powder spraying accuracy requirements, a control model of the air velocity adjustment device was established and a fuzzy proportional-integral-differential (PID) air velocity control system was developed. RESULTS: The simulation results indicate that the wind speed control system exhibits a maximum overshoot of 2.18% and an average response time of 1.48 s. The field experiment conducted in a rubber plantation revealed that when the air-assisted powder sprayer operates in the variable powder spraying mode, the average response time of the control system is 2.5 s. The control accuracy of each executive mechanism exceeded 95.9%. The deposition coefficient of variation (CV) at different canopy heights was relatively consistent, with values of 35.38%, 36.26% and 36.90%. In comparison to the quantitative mode, the variable mode showed a significant 20.03% increase in the effective utilization rate of sulfur powder. CONCLUSION: These research findings provide valuable technical support for the advancement of mechanized variable powder spraying equipment in rubber tree cultivation. © 2024 Society of Chemical Industry.

Oral Hypoxia-Inducible Factor 2α Inhibitor Belzutifan in Ocular von Hippel-Lindau Disease: Subgroup Analysis of the Single-Arm Phase 2 LITESPARK-004 Study.

PURPOSE: To report the efficacy of the oral hypoxia-inducible factor 2α inhibitor belzutifan in participants with von Hippel-Lindau disease-associated retinal hemangioblastomas in the LITESPARK-004 study. DESIGN: Subgroup analysis of the phase 2, single-arm, open-label LITESPARK-004 study. PARTICIPANTS: Adults with 1 or more von Hippel-Lindau disease-associated measurable renal cell carcinoma tumors not requiring immediate surgical intervention were eligible. METHODS: Participants received oral belzutifan 120 mg once daily until disease progression or unacceptable treatment-related toxicity. MAIN OUTCOME MEASURES: Efficacy of belzutifan in retinal hemangioblastomas was a secondary end point, measured as response (improved, stable, or progressed) by independent reading center-certified graders based on color fundus imaging performed every 12 weeks using the investigator's preferred imaging standards. Additional assessments, where available, included OCT and ultra-widefield fluorescein angiography. RESULTS: Among 61 participants in LITESPARK-004, 12 had 1 or more evaluable active retinal hemangioblastomas in 16 eyes at baseline per independent reading center. As of April 1, 2022, the median follow-up for participants with ocular von Hippel-Lindau disease at baseline was 37.3 months. All 16 eyes were graded as improved, with a response rate of 100.0% (95% confidence interval, 79.4%-100%). No new retinal hemangioblastomas or ocular disease progression were reported as of data cutoff date. Eight participants underwent additional multimodal eye assessments performed at the National Institutes of Health study site. Among this subgroup, 10 of 24 hemangioblastomas in 8 eyes of 6 participants measured 500 µm or more in greatest linear dimension at baseline and were analyzed further. All 10 hemangioblastomas had a mean area reduction of 15% or more by month 12 and of 30% or more by month 24. CONCLUSIONS: Belzutifan showed promising activity against ocular von Hippel-Lindau disease, including capacity to control retinal hemangioblastomas, with effects sustained for more than 2 years while treatment is ongoing. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Development of a predictive nomogram for intermediate-risk differentiated thyroid cancer patients after fixed 3.7GBq (100mCi) radioiodine remnant ablation.

Objectives: The objective of this study was to develop a predictive nomogram for intermediate-risk differentiated thyroid cancer (DTC) patients after fixed 3.7GBq (100mCi) radioiodine remnant ablation (RRA). Methods: Data from 265 patients who underwent total thyroidectomy with central lymph node dissection (CND) and received RRA treatment at a single institution between January 2018 and March 2023 were analyzed. Patients with certain exclusion criteria were excluded. Univariate and multivariate logistic regression analyses were performed to identify risk factors for a non-excellent response (non-ER) to RRA. A nomogram was developed based on the risk factors, and its performance was validated using the Bootstrap method with 1,000 resamplings. A web-based dynamic calculator was developed for convenient application of the nomogram. Results: The study included 265 patients with intermediate-risk DTC. Significant differences were found between the ER group and the non-ER group in terms of CLNM>5, Hashimoto's thyroiditis, sTg level, TgAb level (P < 0.05). CLNM>5 and sTg level were identified as independent risk factors for non-ER in multivariate analysis. The nomogram showed high accuracy, with an area under the curve (AUC) of 0.833 (95% CI = 0.770-0.895). The nomogram's predicted probabilities aligned closely with actual clinical outcomes. Conclusions: This study developed a predictive nomogram for intermediate-risk DTC patients after fixed 3.7GBq (100mCi) RRA. The nomogram incorporates CLNM>5 and sTg levels as risk factors for a non-ER response to RRA. The nomogram and web-based calculator can assist in treatment decision-making and improve the precision of prognosis information. Further research and validation are needed.

The Microbiome Protocols eBook initiative: Building a bridge to microbiome research.

The Microbiome Protocols eBook (MPB) serves as a crucial bridge, filling gaps in microbiome protocols for both wet experiments and data analysis. The first edition, launched in 2020, featured 152 meticulously curated protocols, garnering widespread acclaim. We now extend a sincere invitation to researchers to participate in the upcoming 2nd version of MPB, contributing their valuable protocols to advance microbiome research.

Intrathecal Fumagillin Alleviates Chronic Neuropathy-Induced Nociceptive Sensitization and Modulates Spinal Astrocyte-Neuronal Glycolytic and Angiogenic Proteins.

Nociceptive sensitization is accompanied by the upregulation of glycolysis in the central nervous system in neuropathic pain. Growing evidence has demonstrated glycolysis and angiogenesis to be related to the inflammatory processes. This study investigated whether fumagillin inhibits neuropathic pain by regulating glycolysis and angiogenesis. Fumagillin was administered through an intrathecal catheter implanted in rats with chronic constriction injury (CCI) of the sciatic nerve. Nociceptive, behavioral, and immunohistochemical analyses were performed to evaluate the effects of the inhibition of spinal glycolysis-related enzymes and angiogenic factors on CCI-induced neuropathic pain. Fumagillin reduced CCI-induced thermal hyperalgesia and mechanical allodynia from postoperative days (POD) 7 to 14. The expression of angiogenic factors, vascular endothelial growth factor (VEGF) and angiopoietin 2 (ANG2), increased in the ipsilateral lumbar spinal cord dorsal horn (SCDH) following CCI. The glycolysis-related enzymes, pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA) significantly increased in the ipsilateral lumbar SCDH following CCI on POD 7 and 14 compared to those in the control rats. Double immunofluorescence staining indicated that VEGF and PKM2 were predominantly expressed in the astrocytes, whereas ANG2 and LDHA were predominantly expressed in the neurons. Intrathecal infusion of fumagillin significantly reduced the expression of angiogenic factors and glycolytic enzymes upregulated by CCI. The expression of hypoxia-inducible factor-1α (HIF-1α), a crucial transcription factor that regulates angiogenesis and glycolysis, was also upregulated after CCI and inhibited by fumagillin. We concluded that intrathecal fumagillin may reduce the expression of ANG2 and LDHA in neurons and VEGF and PKM2 in the astrocytes of the SCDH, further attenuating spinal angiogenesis in neuropathy-induced nociceptive sensitization. Hence, fumagillin may play a role in the inhibition of peripheral neuropathy-induced neuropathic pain by modulating glycolysis and angiogenesis.