Fufang Zhenshu Tiaozhi capsule enhances bone formation and safeguards against glucocorticoid-induced osteoporosis through innovative Mekk2-mediated ß-catenin deubiquitination.

INTRODUCTION: Bone homeostasis depends on the regulation of ß-catenin in osteoblasts. Glucocorticoids (GCs) are known to diminish ß-catenin activity via Wnt pathway signaling, leading to osteoporosis. Conversely, activating ß-catenin in osteoblasts through mitogen-activated protein kinase kinase kinase 2 (Mekk2) offers an innovative approach to combat GC-induced osteoporosis (GIOP). Fufang Zhenshu Tiaozhi (FTZ) capsules have shown effectiveness in treating GIOP, but the mechanisms behind this are still unclear. MATERIALS AND METHODS: In this study, Mekk2 knockout mice (Mekk2-/-) was generated by CRISPR/Cas9. These mice were then subjected to Alcian Blue-Alizarin Red staining and immunofluorescence to assess their bone and cartilage development. To establish models of GIOP, both Mekk2-/- and wild-type (WT) mice were treated with dexamethasone (DXMS) and subsequently given FTZ capsules. We analyzed the resulting phenotypic changes in these mice using Micro-CT scans and histomorphological studies. Primary osteoblasts, isolated from both Mekk2-/- and WT mice, underwent qRT-PCR to measure key osteogenesis markers, including Runx2, Sp7, Bgalp, Col1a1 and Alp. Cells were then exposed to treatments with either FTZ or Wnt3a and the phosphorylation levels of ß-catenin and Mekk2, along with the protein expression of Runx2, were evaluated using Western blotting and immunoprecipitation. Additionally, C3H10T1/2 cells transfected with TOPflash-luciferase and Renilla luciferase reporters were treated with FTZ and Wnt3a to measure ß-catenin activity. RESULTS: In our study, administering FTZ in vivo effectively prevented bone loss typically induced by GCs. However, it's important to note that this protective effect was substantially reduced in mice lacking Mekk2. Additionally, FTZ showed a significant ability to enhance osteogenic differentiation in primary osteoblasts, doing so by altering the expression of Mekk2. Intriguingly, the impact of FTZ on Mekk2 appears to function through a pathway separate from the traditional Wnt signaling route. Furthermore, our findings indicate that FTZ also promotes the deubiquitination of ß-catenin, contributing further to its positive effects on bone health. CONCLUSIONS: This study suggests that FTZ plays a significant role in protecting bone mass in cases of GIOP. The mechanism through which FTZ confers this benefit involves the activation of Mekk2/ß-catenin signaling pathways, which represents a promising alternative strategy to counteract the deleterious effects of GIOP by augmenting osteoblastogenesis.

Critical COVID-19, Victivallaceae abundance, and celiac disease: A mediation Mendelian randomization study.

Celiac disease exhibits a higher prevalence among patients with coronavirus disease 2019. However, the potential influence of COVID-19 on celiac disease remains uncertain. Considering the significant association between gut microbiota alterations, COVID-19 and celiac disease, the two-step Mendelian randomization method was employed to investigate the genetic causality between COVID-19 and celiac disease, with gut microbiota as the potential mediators. We employed the genome-wide association study to select genetic instrumental variables associated with the exposure. Subsequently, these variables were utilized to evaluate the impact of COVID-19 on the risk of celiac disease and its potential influence on gut microbiota. Employing a two-step Mendelian randomization approach enabled the examination of potential causal relationships, encompassing: 1) the effects of COVID-19 infection, hospitalized COVID-19 and critical COVID-19 on the risk of celiac disease; 2) the influence of gut microbiota on celiac disease; and 3) the mediating impact of the gut microbiota between COVID-19 and the risk of celiac disease. Our findings revealed a significant association between critical COVID-19 and an elevated risk of celiac disease (inverse variance weighted [IVW]: P = 0.035). Furthermore, we observed an inverse correlation between critical COVID-19 and the abundance of Victivallaceae (IVW: P = 0.045). Notably, an increased Victivallaceae abundance exhibits a protective effect against the risk of celiac disease (IVW: P = 0.016). In conclusion, our analysis provides genetic evidence supporting the causal connection between critical COVID-19 and lower Victivallaceae abundance, thereby increasing the risk of celiac disease.

Recent clinical practice guidelines for the management of low back pain: a global comparison.

BACKGROUND: Low back pain (LBP) is a significant health problem worldwide, with a lifetime prevalence of 84% in the general adult population. To rationalise the management of LBP, clinical practice guidelines (CPGs) have been issued in various countries around the world. This study aims to identify and compare the recommendations of recent CPGs for the management of LBP across the world. METHODS: MEDLINE, EMBASE, CINAHL, PEDro, and major guideline databases were searched from 2017 to 2022 to identify CPGs. CPGs focusing on information regarding the management and/or treatment of non-specific LBP were considered eligible. The quality of included guidelines was evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. RESULTS: Our analysis identified a total of 22 CPGs that met the inclusion criteria, and were of middle and high methodological quality as assessed by the AGREE II tool. The guidelines exhibited heterogeneity in their recommendations, particularly in the approach to different stages of LBP. For acute LBP, the guidelines recommended the use of non-steroidal anti-inflammatory drugs (NSAIDs), therapeutic exercise, staying active, and spinal manipulation. For subacute LBP, the guidelines recommended the use of NSAIDs, therapeutic exercise, staying active, and spinal manipulation. For chronic LBP, the guidelines recommended therapeutic exercise, the use of NSAIDs, spinal manipulation, and acupuncture. CONCLUSIONS: Current CPGs provide recommendations for almost all major aspects of the management of LBP, but there is marked heterogeneity between them. Some recommendations lack clarity and overlap with other treatments within the guidelines.

The mechanical, wear, antibacterial properties and biocompatibility of injectable restorative materials under wet challenge.

OBJECTIVES: To evaluate the mechanical, wear, antibacterial properties, and biocompatibility of injectable composite materials. METHODS: Two injectable composite resins (GU and BI), one flowable composite resin (FS), and one flowable compomer (DF), in A2 shade, were tested. Mechanical properties were tested via three-point bending test immediately after preparation and after 1-day, 7-day, 14-day, and 30-day water storage. Under water-PMMA slurry immersion, specimens were subjected to a 3-body wear test (10,000 cycles) against stainless steel balls, while the roughness, wear depth, and volume loss were recorded. After 1-day and 3-day MC3T3-E1 cell culture, cell viability was evaluated with CCK-8 test kits, while the cell morphology was observed under CLSM and SEM. Antibacterial properties on S. mutans were assessed via CFU counting, CLSM, and SEM observation. SPSS 26.0 was used for statistical analysis (α = 0.05). RESULTS: The mechanical properties were material-dependent and sensitive to water storage. Flexural strength ranked GU > FS > BI > DF at all testing levels. Three nanocomposites had better wear properties than DF. No significant difference on 1-day cell viability was found, but DF showed significantly lower cell proliferation than nanocomposites on 3-day assessment. GU and FS had more favourable cell adhesion and morphology. CFU counting revealed no significant difference, while FS presented a slightly thicker biofilm and BI showed relatively lower bacteria density. CONCLUSIONS: Injectable nanocomposites outperformed the compomer regarding mechanical properties, wear resistance, and biocompatibility. The tested materials presented comparable antibacterial behaviours. Flowable resin-based composites' performances are affected by multiple factors, and their compositions can be attributed. CLINICAL SIGNIFICANCE: A profound understanding of the mechanical, wear, and biological properties of the restorative material is imperative for the clinical success of dental restorations. The current study demonstrated superior properties of highly filled injectable composite resins, which imply their wider indications and better long-term clinical performances.

Automatic Shrimp Fry Counting Method Using Multi-Scale Attention Fusion.

Shrimp fry counting is an important task for biomass estimation in aquaculture. Accurate counting of the number of shrimp fry in tanks can not only assess the production of mature shrimp but also assess the density of shrimp fry in the tanks, which is very helpful for the subsequent growth status, transportation management, and yield assessment. However, traditional manual counting methods are often inefficient and prone to counting errors; a more efficient and accurate method for shrimp fry counting is urgently needed. In this paper, we first collected and labeled the images of shrimp fry in breeding tanks according to the constructed experimental environment and generated corresponding density maps using the Gaussian kernel function. Then, we proposed a multi-scale attention fusion-based shrimp fry counting network called the SFCNet. Experiments showed that our proposed SFCNet model reached the optimal performance in terms of shrimp fry counting compared to CNN-based baseline counting models, with MAEs and RMSEs of 3.96 and 4.682, respectively. This approach was able to effectively calculate the number of shrimp fry and provided a better solution for accurately calculating the number of shrimp fry.

The chemical and optical stability evaluation of injectable restorative materials under wet challenge.

OBJECTIVES: To investigate and compare the chemical and optical stability of four restorative composite materials: two injectable resins, one flowable resin and one compomer. METHODS: Two injectable nano-filled composite resins: G-aenial Universal (GU) and Beautifil Injectable XSL (BI), a flowable composite resin: Filtek Supreme Flowable (FS) and a compomer: Dyract Flow (DF), in A2 shade were tested and compared. Water sorption and solubility were conducted according to ISO4049:2019 standard; ICP-OES and F-ion selective electrode were used to test the elemental release; Degree of conversion (DC) was obtained by using FTIR; water contact angle was obtained by static sessile drop method, and a spectrophotometer was used for optical properties (ΔE⁎, ΔL⁎ and TP). SPSS 28.0 was used for statistical analysis and the significant level was pre-set as α = 0.05. RESULTS: GU performed the best in water sorption and solubility, FS had the lowest elemental release, the best colour stability, and the highest DCIM and DC24-h. DF, the compomer had the lowest, and GU and BI, the injectable composites had the largest water contact angle, respectively. Correlations were found between water sorption and water solubility. CONCLUSIONS: The four composite restorative materials showed different chemical and optical behaviours. Overall, composite resins performed better than compomer, while additional laboratory and in vivo tests are necessary to obtain a more comprehensive comparison between injectable and flowable composite resins. Wsp and Wsl are influenced by many common factors, and the values are highly positively related. CLINICAL SIGNIFICANCE: A comprehensive understanding of materials is crucial before selecting materials for clinical practice. Composite resins rather than compomers are recommended because of their exceptional properties, which make them eligible for a wide range of clinical applications and an elongated lifespan.

Ziyuglycoside II attenuated OVX mice bone loss via inflammatory responses and regulation of gut microbiota and SCFAs.

BACKGROUND AND PURPOSE: Osteoporosis (OP) is a frequent clinical problem for the elderly. Traditional Chinese Medicine (TCM) has achieved beneficial results in the treatment of OP. Ziyuglycoside II (ZGS II) is a major active compound of Sanguisorba officinalis L. that has shown anti-inflammation and antioxidation properties, but little information concerning its anti-OP potential is available. Our research aims to investigate the mechanism of ZGS II in ameliorating bone loss by inflammatory responses and regulation of gut microbiota and short chain fatty acids (SCFAs) in ovariectomized (OVX) mice. METHODS: We predicted the mode of ZGS II action on OP through network pharmacology and molecular docking, and an OVX mouse model was employed to validate its anti-OP efficacy. Then we analyzed its impact on bone microstructure, the levels of inflammatory cytokines and pain mediators in serum, inflammation in colon, intestinal barrier, gut microbiota composition and SCFAs in feces. RESULTS: Network pharmacology identified 55 intersecting targets of ZGS II related to OP. Of these, we predicted IGF1 may be the core target, which was successfully docked with ZGS II and showed excellent binding ability. Our in vivo results showed that ZGS II alleviated bone loss in OVX mice, attenuated systemic inflammation, enhanced intestinal barrier, reduced the pain threshold, modulated the abundance of gut microbiota involving norank_f__Muribaculaceae and Dubosiella, and increased the content of acetic acid and propanoic acid in SCFAs. CONCLUSIONS: Our data indicated that ZGS II attenuated bone loss in OVX mice by relieving inflammation and regulating gut microbiota and SCFAs.

A 58-Year-Old Woman with Acute Torsion of the Small Bowel Due to Diffuse Intestinal Lipomatosis.

BACKGROUND Diffuse intestinal lipomatosis is a rare condition that infiltrates mature fatty tissue into the intestinal submucosa and subserosa of the small or large intestine and can present with intestinal obstruction or torsion. This report is of the case of a 58-year-old woman who had acute torsion of the small bowel due to diffuse small intestinal lipomatosis. CASE REPORT A 58-year-old woman, who was otherwise in good health, arrived at our Emergency Department experiencing sudden, intense pain in the lower abdomen. She also reported abdominal swelling, feelings of nausea, vomiting, and reduced ability to defecate for at least 2 days. The next morning, contrast-enhanced abdominal computed tomography (CT) scan was performed, showing diffuse thickening of the small intestinal wall with hypodensity, fatty density, lumen narrowing, and wall thinning. The small intestine demonstrated a whirlpool-like distribution in the lower right abdomen and localized thickening of the small intestinal wall, suggesting acute intestinal torsion. An hour later, an emergency operation was performed to remove part of the small intestine. Three days later, pathological results showed a thin intestinal wall, expansion of the mucosal layer and submucosa, and hyperplasia of adipose tissue. CONCLUSIONS This report presents a rare case of torsion and small bowel obstruction caused by diffuse intestinal lipomatosis and focuses on the abdominal enhanced CT scan, which showed diffuse thickening of the small intestine, with multiple areas of fat density and torsion of the small intestine in the right lower abdomen. Histopathology is also presented, with the result showing intestinal lipomatosis.

Sensory manipulation as a countermeasure to robot teleoperation delays: system and evidence.

In the realm of robotics and automation, robot teleoperation, which facilitates human-machine interaction in distant or hazardous settings, has surged in significance. A persistent issue in this domain is the delays between command issuance and action execution, causing negative repercussions on operator situational awareness, performance, and cognitive load. These delays, particularly in long-distance operations, are difficult to mitigate even with the most advanced computing advancements. Current solutions mainly revolve around machine-based adjustments to combat these delays. However, a notable lacuna remains in harnessing human perceptions for an enhanced subjective teleoperation experience. This paper introduces a novel approach of sensory manipulation for induced human adaptation in delayed teleoperation. Drawing from motor learning and rehabilitation principles, it is posited that strategic sensory manipulation, via altered sensory stimuli, can mitigate the subjective feeling of these delays. The focus is not on introducing new skills or adapting to novel conditions; rather, it leverages prior motor coordination experience in the context of delays. The objective is to reduce the need for extensive training or sophisticated automation designs. A human-centered experiment involving 41 participants was conducted to examine the effects of modified haptic cues in teleoperations with delays. These cues were generated from high-fidelity physics engines using parameters from robot-end sensors or physics engine simulations. The results underscored several benefits, notably the considerable reduction in task time and enhanced user perceptions about visual delays. Real-time haptic feedback, or the anchoring method, emerged as a significant contributor to these benefits, showcasing reduced cognitive load, bolstered self-confidence, and minimized frustration. Beyond the prevalent methods of automation design and training, this research underscores induced human adaptation as a pivotal avenue in robot teleoperation. It seeks to enhance teleoperation efficacy through rapid human adaptation, offering insights beyond just optimizing robotic systems for delay compensations.

mHealth Apps for the Self-Management of Low Back Pain: Systematic Search in App Stores and Content Analysis.

BACKGROUND: With the rapid development of mobile health (mHealth) technology, many health apps have been introduced to the commercial market for people with back pain conditions. However, little is known about their content, quality, approaches to care for low back pain (LBP), and associated risks of use. OBJECTIVE: The aims of this research were to (1) identify apps for the self-management of LBP currently on the market and (2) assess their quality, intervention content, theoretical approaches, and risk-related approaches. METHODS: The UK iTunes and Google Play stores were initially searched for apps related to the self-management of LBP in May 2022. A repeat search in June 2023 was conducted to ensure that any relevant new apps developed in the last year were incorporated into the review. A total of 3 keywords recommended by the Cochrane Back and Neck Group were used to search apps "low back pain," "back pain," and "lumbago." The quality of the apps was assessed by using the 5-point Mobile App Rating Scale (MARS). RESULTS: A total of 69 apps (25 iOS and 44 Android) met the inclusion criteria. These LBP self-management apps mainly provide recommendations on muscle stretching (n=51, 73.9%), muscle strengthening (n=42, 60.9%), core stability exercises (n=32, 46.4%), yoga (n=19, 27.5%), and information about LBP mechanisms (n=17, 24.6%). Most interventions (n=14, 78%) are consistent with the recommendations in the National Institute for Health and Care Excellence (NICE) guidelines. The mean (SD) MARS overall score of included apps was 2.4 (0.44) out of a possible 5 points. The functionality dimension was associated with the highest score (3.0), whereas the engagement and information dimension resulted in the lowest score (2.1). Regarding theoretical and risk-related approaches, 18 (26.1%) of the 69 apps reported the rate of intervention progression, 11 (15.9%) reported safety checks, only 1 (1.4%) reported personalization of care, and none reported the theoretical care model or the age group targeted. CONCLUSIONS: mHealth apps are potentially promising alternatives to help people manage their LBP; however, most of the LBP self-management apps were of poor quality and did not report the theoretical approaches to care and their associated risks. Although nearly all apps reviewed included a component of care listed in the NICE guidelines, the model of care delivery or embracement of care principles such as the application of a biopsychosocial model was unclear.

Three new LmbU targets outside lmb cluster inhibit lincomycin biosynthesis in Streptomyces lincolnensis.

BACKGROUND: Antibiotics biosynthesis is usually regulated by the cluster-situated regulatory gene(s) (CSRG(s)), which directly regulate the genes within the corresponding biosynthetic gene cluster (BGC). Previously, we have demonstrated that LmbU functions as a cluster-situated regulator (CSR) of lincomycin. And it has been found that LmbU regulates twenty non-lmb genes through comparative transcriptomic analysis. However, the regulatory mode of CSRs' targets outside the BGC remains unknown. RESULTS: We screened the targets of LmbU in the whole genome of Streptomyces lincolnensis and found fourteen candidate targets, among which, eight targets can bind to LmbU by electrophoretic mobility shift assays (EMSA). Reporter assays in vivo revealed that LmbU repressed the transcription of SLINC_0469 and SLINC_1037 while activating the transcription of SLINC_8097. In addition, disruptions of SLINC_0469, SLINC_1037, and SLINC_8097 promoted the production of lincomycin, and qRT-PCR showed that SLINC_0469, SLINC_1037, and SLINC_8097 inhibited transcription of the lmb genes, indicating that all the three regulators can negatively regulate lincomycin biosynthesis. CONCLUSIONS: LmbU can directly regulate genes outside the lmb cluster, and these genes can affect both lincomycin biosynthesis and the transcription of lmb genes. Our results first erected the cascade regulatory circuit of LmbU and regulators outside lmb cluster, which provides the theoretical basis for the functional research of LmbU family proteins.

Multifunctional Luminescent 3D Ln-MOFs with High Sensitivity for Trace Detection of Micronutrients.

The synthesis of two versatile fluorescent metal-organic frameworks (MOFs), [Eu(4-NCP)(1,4-bdc)]n·0.5H2O (1) and [Eu(4-NCP)(4,4'-bpdc)]n·0.75H2O (2) (HNCP = 2-(4-carboxyphenyl)imidazo(4,5-f)-(1,10)phenanthroline, 1,4-H2bdc = benzene-1,4-dicarboxylic acid, 4,4'-H2bpdc = 4,4'-biphenyldicarboxylic acid), was carried out using a hydrothermal method. These MOFs were characterized through various advanced technologies to determine their structural information. The results indicate that both MOFs exhibited 3D network structures with specific topologies. Furthermore, these MOFs demonstrated exceptional thermal stabilities and adsorption capabilities. Additionally, complex 2 was utilized for studying the fluorescence sensing properties of various micronutrients including metal ions, nitro aromatic compounds, and biological small molecules. Notably, complex 2 showed promising potential as a multifunctional sensor for selectively detecting Fe3+, nitrobenzene, and ascorbic acid in aqueous solutions through fluorescence quenching with low limits of detection (LODs ∼ 10-7 M) and high quenching constants (Ksv ∼ 103 M-1). Moreover, the detection mechanism of complex 2 was further investigated by using experimental methods and DFT calculations.

Magnetic Hydroxyapatite-Coated Iron-Chromium Microspheres for Dental Surface Polishing and Plaque Removal.

This research aimed to engineer magnetic hydroxyapatite-coated iron-chromium (HAp-FeCr) microspheres to enhance dental surface polishing and plaque elimination. Utilizing a tailored sol-gel approach, the HAp-FeCr microspheres were synthesized and exhaustively characterized via scanning electron microscopy, energy-dispersive X-ray spectroscopy, ζ-potential, X-ray diffractometry, and X-ray photoelectron spectroscopy methodologies. Key findings showcased that these microspheres retained their magnetic properties post-HAp coating, as evidenced by the magnetization curves. An innovative magnetic polishing system was developed, incorporating these microspheres and a 2000 rpm magnet. Comparative evaluations between traditional air-powder polishing and the proposed magnetic technique demonstrated the latter's superiority. Notably, the magnetic polishing led to a substantial reduction in dental plaque on the tooth surface, decreasing bacterial adhesion and early biofilm formation by Streptococcus gordonii and Lactobacillus acidophilus, where the most pronounced effects were observed in samples with elevated HAp content. A significant 60% reduction in dental plaque was achieved with the magnetic method relative to air-powder polishing. Furthermore, the HAp-FeCr microspheres' biocompatibility was verified through cytotoxicity tests and animal studies. In essence, the magnetic HAp-FeCr microspheres present a novel and efficient strategy for dental treatments, holding immense potential for improving oral health.

Comparative survey of coordinated regulation of hypothalamic-pituitary-somatotropic axis in golden pompano (Trachinotus ovatus) and humpback grouper (Cromileptes altivelis).

Hypothalamic-Pituitary-Somatotropic (HPS) axis is the essential endocrine system playing important roles in animal growth. Here, the HPS axis were characterized in golden pompano (Trachinotus ovatus) and humpback grouper (Cromileptes altivelis), two marine cultured tropical teleosts representing fast and slow growth patterns, respectively. Through genomic and transcriptomic survey, 32 and 35 HPS genes were characterized in T. ovatus and C. altivelis. Functional domain and phylogeny revealed their conserved function among teleost lineages, with more ssts and igfbps identified and actively expressed in C. altivelis than in T. ovatus. The regulation of HPS genes responding to external stimuli revealed that T. ovatus HPS genes, including gh, igf1/2, igfbp1a/b, igfbp2b and igfbp5b, were differentially expressed under temperature or starvation challenges, while C. altivelis HPS genes were sensitive to salinity change with sst1.2, ghrhrb, igf1, igf2r, igfbp1a and igfbp5a regulated in brains. Strong interactive connectivity of igfbps was found in both T. ovatus and C. altivelis. Moreover, HPS genes evolved differently between T. ovatus and C. altivelis, and positively selected sites were detected in more C. altivelis HPS genes, like in functional domains of igf1ra and igf1rb. The igf1ra evolved faster than igf1rb in teleosts, which may contribute to their functional divergence. In conclusion, this study represented different regulatory and evolutionary patterns of HPS axis between T. ovatus and C. altivelis, which are vital in regulating their growth and will provide comprehensive insights into the cultivation of T. ovatus and C. altivelis in aquaculture.

Assessing size shifts amidst a warming climate in lakes recharged by the Asian Water Tower through satellite imagery.

Recent studies indicate that the Asian Water Tower (AWT) is at risk due to climate change, which can negatively impact water and food security in Asia. However, there is a lack of comprehensive information on lakes' spatial and temporal changes in this region. This information is crucial for understanding the risk magnitude and designing strategies. To fill this research gap, we analyzed 89,480 Landsat images from 1977 ± 2 to 2020 ± 2 to investigate the changes in the size of lakes recharged by the AWT. Our findings showed that out of the 209 lakes larger than 50 km2, 176 (84 %) grew during the wet season and 167 (81 %) during the dry season. 74 % of expanded lakes are located in the Inner Tibetan Plateau (TP) and Tarim basins. The lakes that shrank are found mainly in the Helmand, Indus, and Yangtze basins. Over the entire period, the area of shrinkage (55,077.028 km2 in wet season, 53,986.796 km2 in dry) markedly exceeded expansion (13,000.267 km2 in wet, 11,038.805 km2 in dry), with the drastic decline of the Aral Sea being a major contributor to shrinkage, accounting for 90 % of the total loss. From 1990 ± 2 to 2020 ± 2, alpine lakes mostly expanded, plain lakes mostly shrank, with the opposite trend from 1977 ± 2 to 1990 ± 2. Glacial loss and permafrost thawing under global warming in the Inner TP, Tarim Interior, Syr Darya, and Mekong basins were strongly correlated with lake expansion. However, permafrost discontinuities may prevent significant growth of lakes in the Indus and Ganges basins despite increased recharge. Our findings point to the prominence of the risk the lakes recharged by AWT face. Taking immediate action to manage these risks and adaptation is crucial as the AWT retreats and lake recharges are slowed.

Which method for femoral component sizing when performing kinematic alignment TKA? An in silico study.

INTRODUCTION: The kinematically alignment (KA) technique for TKA aims to reproduce the pre-arthritic knee anatomy, including both the femoro-tibial and femoro-patellar joints. An in silico study was conducted to compare 3 different femoral component sizing techniques to identify the anatomical landmark which allows closest restoration of the native trochlear anatomy. Our study's question was: what was the best method for sizing the femoral component when performing KA-TKA? It was hypothesized that sizing the femoral component by aiming to restore the groove height would be the best method to restore the native trochlear anatomy. METHODS: GMK sphere® (Medacta) femoral component 3D models were virtually kinematically aligned on 30 tri-dimensional (3D) bony osteoarthritis knee models. The femoral component was mediolaterally positioned to match distal native and prosthetic grooves. Three methods were used to size the femoral component: a conventional method with the anterior femoral cut flush to the femoral cortex (C-KATKA) and two alternative personalized methods aiming to recreate either the medial facet's height (ATM-KATKA) or the groove's height (ATG-KATKA). In-house analysis software was used to compare native and prosthetic trochlear articular surfaces and mediolateral implant overhangs. RESULTS: Compared with the C-KATKA, ATG-KATKA and ATM-KATKA techniques increased the component size by a mean of 0.90 (SD 0.31, min 0.5 to max 1.5) (p<0.001) and 1.02 (SD 0.31, min 0.5 to max 1.5) (p<0.001), respectively. C-KATKA technique substantially proximally understuffed the trochleae with maximum values of 7.11mm (SD 1.39, min 3.93mm to max 10.57mm) in the medial facet, 4.72mm (SD 1.27, min 1.46mm to max 6.86mm) in the lateral facet and 4.51mm (SD 1.40, min 1.92mm to max 7.30mm) in the groove, respectively. Alternative techniques understuffed medial facet with maximum values of 5.07mm (SD 1.29, min 2.83mm to max 8.34mm) and 4.70mm (SD 1.52, min 0.83mm to max 8.04mm) for ATG-KATKA and ATM-KATKA techniques, respectively. There was no significant understuffing of the groove or lateral facet for alternative techniques (ATM and ATG). The ATM-KATKA and ATG-KATKA techniques generated mediolateral implant overhang, mainly postero-lateral, with a rate of 90.0% and 86.7%, respectively. In this study, no mediolateral implant overhang was found for C-KATKA. DISCUSSION/CONCLUSION: The C-KATKA technique substantially understuffs the native trochlear articular surfaces in medial, lateral and groove parts. Alternative techniques (ATM-KATKA and ATG-KATKA) for sizing the femoral component better restore the native trochlear anatomy but also generate a high rate of postero-lateral implant overhangs. Would this postero-lateral implant overhang be clinically deleterious remains unknown? The aspect ratio of contemporary femoral TKA implants can probably be optimized to allow a better anatomical restoration of the anterior femoral compartment. LEVEL OF EVIDENCE: II, in silico study.

Magnaporthe oryzae effector MoSPAB1 directly activates rice Bsr-d1 expression to facilitate pathogenesis.

Fungal pathogens typically use secreted effector proteins to suppress host immune activators to facilitate invasion. However, there is rarely evidence supporting the idea that fungal secretory proteins contribute to pathogenesis by transactivating host genes that suppress defense. We previously found that pathogen Magnaporthe oryzae induces rice Bsr-d1 to facilitate infection and hypothesized that a fungal effector mediates this induction. Here, we report that MoSPAB1 secreted by M. oryzae directly binds to the Bsr-d1 promoter to induce its expression, facilitating pathogenesis. Amino acids 103-123 of MoSPAB1 are required for its binding to the Bsr-d1 promoter. Both MoSPAB1 and rice MYBS1 compete for binding to the Bsr-d1 promoter to regulate Bsr-d1 expression. Furthermore, MoSPAB1 homologues are highly conserved among fungi. In particular, Colletotrichum fructicola CfSPAB1 and Colletotrichum sublineola CsSPAB1 activate kiwifruit AcBsr-d1 and sorghum SbBsr-d1 respectively, to facilitate pathogenesis. Taken together, our findings reveal a conserved module that may be widely utilized by fungi to enhance pathogenesis.

Enhancing Zn2+ Storage Performance by Constructing the Interfaces Between VO2 and Co-N-C Layers.

Vanadium oxides have aroused attention as cathode materials in aqueous zinc-ion batteries (AZIBs) due to their low cost and high safety. However, low ion diffusion and vanadium dissolution often lead to capacity decay and deteriorating stability during cycling. Herein, vanadium dioxides (VO2 ) nanobelts are coated with a single-atom cobalt dispersed N-doped carbon (Co-N-C) layer via a facile calcination strategy to form Co-N-C layer coated VO2 nanobelts (VO2 @Co-N-C NBs) for cathodes in AZIBs. Various in-/ex situ characterizations demonstrate the interfaces between VO2 layers and Co-N-C layers can protect the VO2 NBs from collapsing, increase ion diffusion, and enhance the Zn2+ storage performance. Additional density functional theory (DFT) simulations demonstrate that Co─O─V bonds between VO2 and Co-N-C layers can enhance interfacial Zn2+ storage. Moreover, the VO2 @Co-N-C NBs provided an ultrahigh capacity (418.7 mAh g-1 at 1 A g-1 ), outstanding long-term stability (over 8000 cycles at 20 A g-1 ), and superior rate performance.

Decoding the mechanism of Eleutheroside E in treating osteoporosis via network pharmacological analysis and molecular docking of osteoclast-related genes and gut microbiota.

Objective: Eleutheroside E (EE) is an anti-inflammatory natural compound derived from the edible medicinal herb Acanthopanax senticosus. This study aims to investigate the underlying mechanism of the anti-osteoporosis action of EE through network pharmacology, molecular docking and gut microbiota. Materials and methods: Network pharmacology was used to explore the potential core targets and main pathways mediated by EE in osteoporosis (OP) treatment. Molecular docking was exploited to investigate the interactions between the active anti-OP compounds in EE and the potential downstream targets. Following the multi-approach bioinformatics analysis, ovariectomy (OVX) model was also established to investigate the in vivo anti-OP effects of EE. Results: The top 10 core targets in PPI network were TP53, AKT1, JUN, CTNNB1, STAT3, HIF1A, EP300, CREB1, IL1B and ESR1. Molecular docking results that the binding energy of target proteins and the active compounds was approximately between -5.0 and -7.0 kcal/mol, which EE has the lowest docking binding energy with HIF1A. Enrichment analysis of GO and KEGG pathways of target proteins indicated that EE treatment could potentially alter numerous biological processes and cellular pathways. In vivo experiments demonstrated the protective effect of EE treatment against accelerated bone loss, where reduced serum levels of TRAP, CTX, TNF-α, LPS, and IL-6 and increased bone volume and serum levels of P1NP were observed in EE-treated mice. In addition, changes in gut microbiota were spotted by 16S rRNA gene sequencing, showing that EE treatment increased the relative abundance of Lactobacillus and decreased the relative abundance of Clostridiaceae. Conclusion: In summary, these findings suggested that the characteristics of multi-target and multi-pathway of EE against OP. In vivo, EE prevents the onset of OP by regulating gut microbiota and inflammatory response and is therefore a potential OP drug.

Nuclear receptor corepressor 1 deficiency exacerbates asthma by modulating macrophage polarization.

Macrophage polarization plays an important role in asthma. Nuclear receptor corepressor 1 (NCOR1) plays an important role in metabolic and cardiovascular diseases by regulating the function of macrophages. The aim of this research was to examine the role and mechanism of macrophage NCOR1 in the development of asthma. We used ovalbumin (OVA) to induce macrophage NCOR1-deficient mice for asthma formation. Our results revealed that macrophage NCOR1 deficiency markedly enhanced allergic airway inflammation. In addition, NCOR1 deficiency in macrophages was found to enhance M2 polarization. Mechanistic studies suggested that NCOR1 promoted macrophage polarization by interacting with PPARγ, contributing to the pathogenesis of asthma. In conclusion, macrophage NCOR1 deficiency promoted the regulation of M2 programming by enhancing PPARγ expression to exacerbate asthma. Macrophage NCOR1 might be a potential target for the treatment of asthma.