Regional disparities, age-related changes and sex-related differences in knee osteoarthritis.

BACKGROUND: The objective of the study is to analyse the regions, age and sex differences in the incidence of knee osteoarthritis (KOA). METHODS: Data were extracted from the global burden of diseases (GBD) 2019 study, including incidence, years lived with disability (YLD), disability-adjusted life-years (DALYs) and risk factors. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in age standardized rate (ASR) of KOA. Paired t-test, paired Wilcoxon signed-rank test and spearman correlation were performed to analyze the association of sex disparity in KOA and socio-demographic index (SDI). RESULTS: There were significant regional differences in the incidence of knee osteoarthritis. In 2019, South Korea had the highest incidence of knee osteoarthritis (474.85,95%UI:413.34-539.64) and Thailand had the highest increase in incidence of knee osteoarthritis (EAPC = 0.56, 95%CI = 0.54-0.58). Notably, higher incidence, YLD and DALYs of knee osteoarthritis were associated with areas with a high socio-demographic index (r = 0.336, p < 0.001; r = 0.324, p < 0.001; r = 0.324, p < 0.001). In terms of age differences, the greatest increase in the incidence of knee osteoarthritis was between the 35-39 and 40-44 age groups. (EAPC = 0.52, 95%CI = 0.40-0.63; 0.47, 95%CI = 0.36-0.58). In addition, there were significant sex differences in the disease burden of knee osteoarthritis (P < 0.001). CONCLUSIONS: The incidence of knee osteoarthritis is significantly different with regions, age and sex.

Effects of cadmium and zinc interactions on the physiological biochemistry and enrichment characteristics of Iris pseudacorus.

Compound pollution with cadmium (Cd) and zinc (Zn) is common in nature. The effects of compounded Cd and Zn on the growth and development of Iris pseudacorus in the environment and the plant's potential to remediate heavy metals in the environment remain unclear. In this study, the effects of single and combined Cd and Zn stress on I. pseudacorus growth and the enrichment of heavy metals in I. pseudacorus seedlings were investigated. The results showed that under Cd (160 µM) and Zn (800 µM) stress, plant growth was significantly inhibited and photosynthetic performance was affected. Cd+Zn200 (160 µM + 200 µM) reduced the levels of malondialdehyde, hydrogen peroxide, and non-protein thiols by 31.29%, 53.20%, and 13.29%, respectively, in the aboveground tissues compared with levels in the single Cd treatment. However, Cd+Zn800 (160 µM + 800 µM) had no effect. Cd and Zn800 inhibited the absorption of mineral elements, while Zn200 had little effect on plants. Compared with that for Cd treatment alone, Cd + Zn200 and Cd+Zn800 reduced the Cd content in aboveground tissues by 54.15% and 49.92%, respectively, but had no significant effect on Cd in the root system. Zn significantly reduced the Cd content in subcellular components and limited the content and proportion of Cd extracted using water and ethanol. These results suggest that a low supply of Zn reduces Cd accumulation in aboveground tissues by promoting antioxidant substances and heavy metal chelating agents, thus protecting the photosynthetic systems. The addition of Zn also reduced the mobility and bioavailability of Cd to alleviate its toxicity in I. pseudacorus.

Gender and socioeconomic disparities in global burden of chronic kidney disease due to glomerulonephritis: A global analysis.

AIM: To investigate the gender and socioeconomic disparities in the global burden of chronic kidney disease (CKD) due to glomerulonephritis from 1990 to 2019. METHODS: Data were extracted from the global burden of diseases (GBD) 2019 study, including incidence, prevalence and disability-adjusted life-years (DALYs). Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in age-standardized rate (ASR) of CKD due to glomerulonephritis. Paired t-test, paired Wilcoxon signed-rank test and Spearman correlation were performed to analyse the association and gender disparity in CKD due to glomerulonephritis. RESULTS: Globally, incident cases of CKD due to glomerulonephritis increased 81% from 9 557 397 in 1990 to 17 308 071 in 2019. The age-standardized incidence rate increased by 1.47 compared with 1990 and DALYs increased by 1.35 compared with 1990 (per 100 000). The number of patients with CKD due to glomerulonephritis in low-middle SDI (3829917) and middle SDI (6268817) regions accounts for more than 55% of the total cases. CKD due to glomerulonephritis caused a higher burden including the incidence rate (p < .0001) and DALY rate (p < .0001) in men compared to women. The age-standardized DALY rate was negatively correlated with SDI (ρ = -0.64, p < .001). In the analysis of risk factors for DALYs, male individuals had a larger burden of hypertension, high BMI and high sodium diet in the DALY rates than female subjects. CONCLUSION: The burden of CKD due to glomerulonephritis was more skewed towards developing and less developed economies and differed by gender, so certain nations should implement far more focused and targeted policies.

Oral and Maxillofacial Autologous Fat Transplantation: History, Clinical Application Status and Research Progress.

After more than a century of development, autologous fat transplantation (AFT), a repair method for soft tissue defects and deformities, has the advantages of being simple, rapid, effective and safe, and it is increasingly favoured by plastic surgeons. This article reviews the developmental history of AFT, analyses its clinical application status in the oral and maxillofacial regions, and provides a preliminary summary and discussion of the research progress related to AFT. The hope is that that this technique could be widely applied for oral and maxillofacial diseases as well as facial rejuvenation indications. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Sensitivity, Noise and Resolution in a BEOL-Modified Foundry-Made ISFET with Miniaturized Reference Electrode for Wearable Point-of-Care Applications.

Ion-sensitive field-effect transistors (ISFETs) form a high sensitivity and scalable class of sensors, compatible with advanced complementary metal-oxide semiconductor (CMOS) processes. Despite many previous demonstrations about their merits as low-power integrated sensors, very little is known about their noise characterization when being operated in a liquid gate configuration. The noise characteristics in various regimes of their operation are important to select the most suitable conditions for signal-to-noise ratio (SNR) and power consumption. This work reports systematic DC, transient, and noise characterizations and models of a back-end of line (BEOL)-modified foundry-made ISFET used as pH sensor. The aim is to determine the sensor sensitivity and resolution to pH changes and to calibrate numerical and lumped element models, capable of supporting the interpretation of the experimental findings. The experimental sensitivity is approximately 40 mV/pH with a normalized resolution of 5 mpH per µm2, in agreement with the literature state of the art. Differences in the drain current noise spectra between the ISFET and MOSFET configurations of the same device at low currents (weak inversion) suggest that the chemical noise produced by the random binding/unbinding of the H+ ions on the sensor surface is likely the dominant noise contribution in this regime. In contrast, at high currents (strong inversion), the two configurations provide similar drain noise levels suggesting that the noise originates in the underlying FET rather than in the sensing region.

Isomeric Effect on Optoelectronic Properties and Photovoltaic Performance of Anthraquinone-Core Perylene Diimide (PDI) and Helical PDI dimers.

Isomerism heavily influences the optoelectronic properties and self-assembly behavior of compounds and subsequently affects their device performance. Herein, two pairs of isomeric perylene diimide (PDI) dimers, PDI and PDI2, were designed and synthesized. The electron-deficient 9,10-anthraquinone group was employed as the bridge, and thus, the resultant dimers exhibited an acceptor-acceptor-acceptor (A-A-A) structure. To determine the isomeric effects on the optoelectronic properties and photovoltaic performance of these dimers, their absorptivity, luminescence, and redox behavior were studied. Bulk heterojunction organic solar cells based on these four dimers were fabricated and measured. The two PDI dimers exhibited clear differences in photovoltaic performance, whereas the two PDI2 analogues showed similar power conversion efficiencies (PCEs). The PCEs of the two PDI2 dimers are much higher than those of the PDI dimers. These results illustrate that the isomeric effect of PDI dimers is much larger than that of PDI2 dimers on the device performance, and proper expansion of conjugation could improve the device performance.

Structural basis for the photoconversion of a phytochrome to the activated Pfr form.

Phytochromes are a collection of bilin-containing photoreceptors that regulate numerous photoresponses in plants and microorganisms through their ability to photointerconvert between a red-light-absorbing, ground state (Pr) and a far-red-light-absorbing, photoactivated state (Pfr). Although the structures of several phytochromes as Pr have been determined, little is known about the structure of Pfr and how it initiates signalling. Here we describe the three-dimensional solution structure of the bilin-binding domain as Pfr, using the cyanobacterial phytochrome from Synechococcus OSB'. Contrary to predictions, light-induced rotation of the A pyrrole ring but not the D ring is the primary motion of the chromophore during photoconversion. Subsequent rearrangements within the protein then affect intradomain and interdomain contact sites within the phytochrome dimer. On the basis of our models, we propose that phytochromes act by propagating reversible light-driven conformational changes in the bilin to altered contacts between the adjacent output domains, which in most phytochromes direct differential phosphotransfer.

[Assessment of Serum IgG and Its Subclasses in Cystic Echinococcosis Patients and Its Application for Diagnosis].

OBJECTIVE: To assess the diagnostic performance of hydatid cyst fluid (HCF) in detecting the anti-HCF IgG and its subclasses IgG1, IgG2 and IgG4 in serum of cystic echinococcosis patients. METHODS: ELISA was used to measure IgG and its subclasses IgG1, IgG2, and IgG4 specific for Echinococcus granulosus HCF, in the sera of 37 cystic echinococcosis (CE) patients and 29 healthy subjects in Huan County, Gansu Province. The receiver operating characteristic (ROC) curves of the four antibodies were analyzed by MedCalc software, referenced with the gold-standard B ultrasonic imaging. The diagnostic performances between the four antibodies were compared using paired z statistics based on the areas under the curve (AUC), and the best diagnostic threshold was determined for each. The sensitivity and specificity for detecting the four types of antibodies were compared using Chi-square test. RESULTS: The AUCs for IgG and its subclasses IgG1, IgG2, and IgG4 were 0.722, 0.919, 0.712, and 0.835, respectively; the AUC of IgG1 was significantly higher than those of IgG (z = 3.629, P < 0.05) and IgG2 (z = 3.292, P<0.05). The sensitivity for detecting IgG, IgGl, IgG2, and IgG4 was 54.1%, 91.9%, 67.6%, and 75.7%, respectively; the sensitivity for IgGl was significantly higher than that for IgG (χ2 = 3.84, P < 0.05), IgG2 (χ2 = 6.80, P < 0.05), and IgG4 (χ2 = 10.16, P < 0.05). The specificity for the four antibodies was 89.7%, 82.8%, 72.4%, and 89.7%, respectively, and no significant difference was found between them. In addition, the sensitivity for detecting IgG4 antibody was significantly higher in CE I-III than in CE IV-V patients. CONCLUSION: The IgG1 antibody shows the highest detection sensitivity by HCF, thus having potential value in diagnosis of cystic echinococcosis.

Structure-guided engineering of plant phytochrome B with altered photochemistry and light signaling.

Phytochromes (phys) encompass a diverse collection of biliproteins that enable cellular light perception by photoconverting between a red-light-absorbing ground state (Pr) and a far-red light-absorbing active state (Pfr). Based on the central role of plant phys in controlling numerous agriculturally important processes, their rational redesign offers great promise toward accelerating crop improvement. Employing as templates the available three-dimensional models of the photosensory module within bacterial phys, we report here our initial attempt to apply structure-guided mutagenesis to phy engineering using Arabidopsis (Arabidopsis thaliana) phyB, the dominant isoform in light-grown plants, as the example. A collection of phyB mutants was generated affecting the bilin-binding pocket that altered photochemistry, thermal stability, and/or nuclear localization patterns, some of which also impacted phenotypic outputs. Of particular interest are the Y361F substitution, which created Arabidopsis plants with greatly enhanced light sensitivity, mutants variably altered in Pfr-to-Pr thermal reversion and nuclear aggregation, and the D307A substitution, which failed to photoconvert from Pr to Pfr and display light-induced nuclear aggregation but retained some biological activity and accelerated turnover in red light. Taken together, this collection provides variants potentially useful to agriculture as well as new tools to better understand the molecular mechanisms underpinning phy signaling.

Do institutional contingencies matter for green investment?-An institution based view of Chinese listed companies.

Current research in the field of environmental management has placed significant emphasis on understanding the reasons behind varying organizational responses to environmental responsibilities. Governance scholars emphasize the central role of institutional factors in shaping environmental responsibilities, primarily due to the substantial influence exerted by regulatory institutions. Drawing on institutional theory, we investigate how sub-national institutional factors impact a firm's green investment intensity and explore their moderating influence on the relationship between green investment and a firm's financial performance. Using a database of Chinese listed companies from 2012 to 2019, this study employs fixed effect model as a baseline regression. Our analysis demonstrates that sub-national institutions, such as state-owned enterprises (SOEs), regional development, and cross-listing, have significant and positive impact on corporate green investment. Our study further provide an evidence that green investment significantly improve firms' financial performance. Moreover, the positive effect of green investment on financial performance is stronger in SOEs and in firms of developed regions as compared to their counterparts, and weaker in cross listed firms than those of non-cross listed peers. Our study suggest that subnational institutions play an imperative role in improving environmental quality and financial performance by promoting corporate green investment. To make sure that our findings remain robust to endogeneity, we applied generalized method of moments (GMM) and propensity score matching (PSM) method. Our findings further provide implications for emerging economies with similar shareholding patterns and unbalanced regional development.

Evaluating the drivers of B2B performance: An empirical analysis based on Alibaba.

The rapid development of B2B has brought about fierce competition among suppliers, and how to gain customer attention and improve performance has become a common concern in academia and industry. This study examined the drivers and mechanisms of B2B performance from an enterprise capability perspective. We collected transaction and enterprise data from 325 suppliers on Alibaba 1688 platform and constructed a structural equation model (SEM). Results showed that supplier service capability, logistics capability, and production capacity all positively impacted B2B performance through the mediating role of customer attention. In addition, we found that service and logistics capabilities are more critical for attracting customer attention for Original Equipment Manufacturer (OEM) suppliers than for non-OEM suppliers. The findings contribute to understanding B2B commerce and provide constructive directions for B2B suppliers to improve their performance.

Towards sustainable management: Exploring the role of internal monitoring in pollution prevention.

Researchers in the field of sustainable management have recently dedicated significant efforts to understand why organizations exhibit diverse responses to environmental responsibilities. Ethical scholars assert that internal management plays a pivotal role in promoting sustainability because of its attitude toward sustainable issues. In alignment with this perspective, our study formulates a framework for internal monitoring that underscores the significance of independent, female, international, and politically connected directors. We investigate how these internal monitors influence a company's commitment to promote sustainable investments for pollution prevention. By employing fixed effect model and generalized method of moments (GMM) on a dataset obtained from the largest emerging market-China over the period 2012 to 2019, our findings indicate that the mentioned monitors demonstrate a stronger commitment to pollution prevention by promoting corporate sustainable investments. In addition, our analysis reveals that when the government withdraws its involvement in enterprises, it has a notable negative impact on the connection between internal monitors and a company's efforts in pollution prevention. Our results imply that implementation of sustainable policies for pollution prevention fundamentally result from not only internal management, but also from powerful stakeholders (like government involvement). Moreover, our study educates the policy makers regarding the social consequences of governmental withdrawal.

Comprehensive repair of the alveolar cleft using cortical and cancellous bone layers: A retrospective study.

To retrospectively review the clinical effect of comprehensive treatment of alveolar cleft (CTAC) using the mandible as the bone source. Patients with alveolar clefts who met the inclusion criteria were subjected to a CTAC protocol that included the following: (1) preoperative orthodontic treatment for creating good soft-tissue conditions; (2) 'area-like grafting' with subperiosteal osteogenic chin bone instead of cartilaginous osteogenic iliac bone; (3) simulation of normal bone anatomy via a sandwich-like bone graft consisting of 'cortical bone + cancellous bone + cortical bone'; and (4) strong internal fixation to ensure initial bone block stability. At 6 months postoperatively, the titanium plate was removed and cone-beam computed tomography was performed to evaluate the surgical results. A total of 54 patients underwent treatment with the CTAC protocol. The average age at the initial operation was 10.3 ± 2.1 years, and the average hospital stay was 2.8 ± 0.6 days. At 6 months postoperatively, 49 patients (90.7%) showed good clinical results. The transplanted bone block formed a 'cortical bone + cancellous bone + cortical bone' structure similar to that of the normal jawbone. A mature bone bridge formed, and the impacted permanent teeth continued to erupt and enter the bone graft area. CTAC is a comprehensive restorative solution for alveolar cleft repair that integrates multiple concepts, including orthodontics, embryology, anatomy, and improvements to surgical methods. The method is easy to perform, causes little surgical trauma, and shows a stable success rate, and is thus worth promoting.

Quaternary organization of a phytochrome dimer as revealed by cryoelectron microscopy.

Phytochromes are a collection of dimeric photoreceptors that direct a diverse array of responses in plants and microorganisms through photoconversion between a red light-absorbing ground state Pr, and a far-red light-absorbing photoactivated state Pfr. Photoconversion from Pr to Pfr is initiated by a light-driven rotation within the covalently attached bilin, which then triggers a series of protein conformational changes in the binding pocket. These movements ultimately affect an appended output module, which often has reversible protein kinase activity. Propagation of the light signal from the bilin to the output module likely depends on the dimerization interface but its architecture and response to phototransformation remain unclear. Here, we used single particle cryoelectron microscopy to determine the quaternary arrangement of the phytochrome dimer as Pr, using the bacteriophytochrome (BphP) from Deinococcus radiodurans. Contrary to the long-standing view that the two monomers are held together solely via their C-terminal region, we provide unambiguous evidence that the N-terminal bilin-binding region of BphP also provides a dimerization interface with the C-terminal kinase domain appearing as a more flexible appendage. The BphP monomers dimerize in parallel with the polypeptides intimately twisting around each other in a right-handed fashion. Based on this electron microscopic picture, we propose that the light-driven conformational changes transmitted from the chromophore to the output module along the spine of this extensive dimer interface is the central feature underpinning phytochrome signaling.

Identification of Fungicide Combinations Targeting Plasmopara viticola and Botrytis cinerea Fungicide Resistance Using Machine Learning.

Downy mildew (caused by Plasmopara viticola) and gray mold (caused by Botrytis cinerea) are fungal diseases that significantly impact grape production globally. Cytochrome b plays a significant role in the mitochondrial respiratory chain of the two fungi that cause these diseases and is a key target for quinone outside inhibitor (QoI)-based fungicide development. Since the mode of action (MOA) of QoI fungicides is restricted to a single active site, the risk of developing resistance to these fungicides is deemed high. Consequently, using a combination of fungicides is considered an effective way to reduce the development of QoI resistance. Currently, there is little information available to help in the selection of appropriate fungicides. This study used a combination of in silico simulations and quantitative structure-activity relationship (QSAR) machine learning algorithms to screen the most potent QoI-based fungicide combinations for wild-type (WT) and the G143A mutation of fungal cytochrome b. Based on in silico studies, mandestrobin emerged as the top binder for both WT Plasmopara viticola and WT Botrytis cinerea cytochrome b. Famoxadone appeared to be a versatile binder for G143A-mutated cytochrome b of both Plasmopara viticola and Botrytis cinerea. Thiram emerged as a reasonable, low-risk non-QoI fungicide that works on WT and G143A-mutated versions of both fungi. QSAR analysis revealed fenpropidin, fenoxanil, and ethaboxam non-QoIs to have a high affinity for G143A-mutated cytochrome b of Plasmopara viticola and Botrytis cinerea. Above-QoI and non-QoI fungicides can be considered for field studies in a fungicide management program against Plasmopara viticola- and Botrytis cinerea-based fungal infections.

Identification of Fungicide Combinations for Overcoming Plasmopara viticola and Botrytis cinerea Fungicide Resistance.

Fungal diseases, including downy mildew (caused by Plasmopara viticola) and gray mold (caused by Botrytis cinerea), significantly impact the marketable yield of grapes produced worldwide. Cytochrome b of the mitochondrial respiratory chain of these two fungi is a key target for Quinone outside inhibitor (QoI)-based fungicide development. Since the mode of action (MOA) of QoI fungicides is restricted to a single site, the extensive usage of these fungicides has resulted in fungicide resistance. The use of fungicide combinations with multiple targets is an effective way to counter and slow down the development of fungicide resistance. Due to the high cost of in planta trials, in silico techniques can be used for the rapid screening of potential fungicides. In this study, a combination of in silico simulations that include Schrödinger Glide docking, molecular dynamics, and Molecular Mechanism-Generalized Born Surface Area calculation were used to screen the most potent QoI and non-QoI-based fungicide combinations to wild-type, G143A-mutated, F129L-mutated, and double-mutated versions that had both G143A and F129L mutations of fungal cytochrome b. In silico docking studies indicated that mandestrobin, famoxadone, captan, and thiram have a high affinity toward WT cytochrome b of Botrytis cinerea. Although the QoIs mandestrobin and famoxadone were effective for WT based on in vitro results, they were not broadly effective against G143A-mutated isolates. Famoxadone was only effective against one isolate with G143A-mutated cytochrome b. The non-QoI fungicides thiram and captan were effective against both WT and isolates with G143A-mutated cytochrome b. Follow-up in silico docking and molecular dynamics studies suggested that fungicide combinations consisting of famoxadone, mandestrobin, fenamidone, and thiram should be considered in field testing targeting Plasmopara viticola and Botrytis cinerea fungicide resistance.

Montelukast and Telmisartan as Inhibitors of SARS-CoV-2 Omicron Variant.

Earlier studies with montelukast (M) and telmisartan (T) have revealed their potential antiviral properties against SARS-CoV-2 wild-type (WT) but have not assessed their efficacy against emerging Variants of Concern (VOCs) such as Omicron. Our research fills this gap by investigating these drugs' impact on VOCs, a topic that current scientific literature has largely overlooked. We employed computational methodologies, including molecular mechanics and machine learning tools, to identify drugs that could potentially disrupt the SARS-CoV-2 spike RBD-ACE2 protein interaction. This led to the identification of two FDA-approved small molecule drugs, M and T, conventionally used for treating asthma and hypertension, respectively. Our study presents an additional potential use for these drugs as antivirals. Our results show that both M and T can inhibit not only the WT SARS-CoV-2 but also, in the case of M, the Omicron variant, without reaching cytotoxic concentrations. This novel finding fills an existing gap in the literature and introduces the possibility of repurposing these drugs for SARS-CoV-2 VOCs, an essential step in responding to the evolving global pandemic.

HIF-1α-Induced Mitophagy Regulates the Regenerative Outcomes of Stem Cells in Fat Transplantation.

Hypoxia is a crucial factor with type diversity that plays an important role in stem cell transplantation. However, the effects of hypoxia on adipose-derived stem cells (ADSCs) are largely unclear in the autologous fat transplantation (AFT) model, which shows a special type of "acute-progressively resolving hypoxia." Here, an AFT model in nude mice and a hypoxic culture model for ADSCs were combined to explore the link between hypoxia-inducible factor-1 α subunit (HIF-1α) and mitophagy under hypoxic conditions. The results showed that the activity of ADSCs in the first 7 days after grafting was the key stage for volume retention, and the expression of HIF-1α, light chain 3 beta (LC3B), and Beclin1 in ADSCs increased during this period. We also found that hypoxia for longer than 48 h damaged the differentiation and mitochondrial respiration of ADSCs in vitro, but hypoxia signals also activate HIF-1α to initiate mitophagy and maintain the activities of ADSCs. Pre-enhancing mitophagy by rapamycin effectively improves mitochondrial respiration in ADSCs after grafting and ultimately improves AFT outcomes.

Targeting plant UBX proteins: AI-enhanced lessons from distant cousins.

Across all eukaryotic kingdoms, ubiquitin regulatory X (UBX) domain-containing adaptor proteins control the segregase cell division control protein 48 (CDC48), and thereby also control cellular proteostasis and adaptation. The structures and biological roles of UBX proteins in animals and fungi have garnered considerable attention. However, their counterparts in plants remain markedly understudied. Since 2021, the artificial intelligence (AI)-based algorithm AlphaFold has provided predictions of protein structural features that can be highly accurate. Predictions of the proteomes of all major model organisms are now freely accessible to the entire research community through user-friendly web interfaces. We propose that the combination of cross-kingdom comparison with AF analysis produces a wealth of testable hypotheses to inspire and guide experimental research on plant UBX domain-containing (PUX) proteins.