[Retracted] Association between vascular endothelial growth factor gene polymorphisms and the risk of osteonecrosis of the femoral head: Systematic review.

[This retracts the article DOI: 10.3892/br.2015.527.].

Robotic-assisted low anterior resection for rectal cancer shows similar clinical efficacy to laparoscopic surgery: A propensity score matched study.

BACKGROUND: Rectal cancer ranks as the second leading cause of cancer-related mortality worldwide, necessitating surgical resection as the sole treatment option. Over the years, there has been a growing adoption of minimally invasive surgical techniques such as robotic and laparoscopic approaches. Robotic surgery represents an innovative modality that effectively addresses the limitations associated with traditional laparoscopic techniques. While previous studies have reported favorable perioperative outcomes for robot-assisted radical resection in rectal cancer patients, further evidence regarding its oncological safety is still warranted. AIM: To conduct a comparative analysis of perioperative and oncological outcomes between robot-assisted and laparoscopic-assisted low anterior resection (LALAR) procedures. METHODS: The clinical data of 125 patients who underwent robot-assisted low anterior resection (RALAR) and 279 patients who underwent LALAR resection at Shandong Provincial Hospital Affiliated to Shandong First Medical University from December 2019 to November 2022 were retrospectively analyzed. After performing a 1:1 propensity score matching, the patients were divided into two groups: The RALAR group and the LALAR group (111 cases in each group). Subsequently, a comparison was made between the short-term outcomes within 30 d after surgery and the 3-year survival outcomes of these two groups. RESULTS: Compared to the LALAR group, the RALAR group exhibited a significantly earlier time to first flatus [2 (2-2) d vs 3 (3-3) d, P = 0.000], as well as a shorter time to first fluid diet [4 (3-4) d vs 5 (4-6) d, P = 0.001]. Additionally, the RALAR group demonstrated reduced postoperative indwelling catheter time [2 (1-3) d vs 4 (3-5) d, P = 0.000] and decreased length of hospital stay after surgery [5 (5-7) d vs 7(6-8) d, P = 0.009]. Moreover, there was an observed increase in total cost of hospitalization for the RALAR group compared to the LALAR group [10777 (10780-11850) dollars vs 10550 (8766-11715) dollars, P = 0.012]. No significant differences were found in terms of conversion rate to laparotomy or incidence of postoperative complications between both groups. Furthermore, no significant disparities were noted regarding the 3-year overall survival rate and 3-year disease-free survival rate between both groups. CONCLUSION: Robotic surgery offers potential advantages in terms of accelerated recovery of gastrointestinal and urologic function compared to LALAR resection, while maintaining similar perioperative and 3-year oncological outcomes.

KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis.

OBJECTIVE: Precancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood. DESIGN: An integrated analysis of genes associated with metaplasia, dysplasia was conducted, verified and characterised in the gastric tissues of patients by single-cell RNA sequencing and immunostaining. Multiple mouse models, including homozygous conditional knockout Klhl21-floxed mice, were generated to investigate the role of Klhl21 deletion in stemness, DNA damage and tumour formation. Mass-spectrometry-based proteomics and ribosome sequencing were used to elucidate the underlying molecular mechanisms. RESULTS: Kelch-like protein 21 (KLHL21) expression progressively decreased in metaplasia, dysplasia and cancer. Genetic deletion of Klhl21 enhances the rapid proliferation of Mist1+ cells and their descendant cells. Klhl21 loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signalling. Increased STAT3 activity was confirmed in cancer cells lacking KLHL21, boosting self-renewal and tumourigenicity. Mechanistically, the loss of KLHL21 promotes PIK3CB mRNA translation by stabilising the PABPC1-eIF4G complex, subsequently causing STAT3 activation. Pharmacological STAT3 inhibition by TTI-101 elicited anticancer effects, effectively impeding the transition from metaplasia to dysplasia. In patients with gastric cancer, low levels of KLHL21 had a shorter survival rate and a worse response to adjuvant chemotherapy. CONCLUSIONS: Our findings highlighted that KLHL21 loss triggers STAT3 reactivation through PABPC1-mediated PIK3CB translational activation, and targeting STAT3 can reverse preneoplastic metaplasia in KLHL21-deficient stomachs.

The clinical and predictive value of 18F-FDG PET/CT metabolic patterns in a clinical Chinese cohort with autoimmune encephalitis.

AIMS: To investigate the diagnostic and predictive role of 18F-FDG PET/CT in patients with autoimmune encephalitis (AE) as a whole group. METHODS: Thrty-five patients (20 females and 15 males) with AE were recruited. A voxel-to-voxel semi-quantitative analysis based on SPM12 was used to analyze 18F-FDG PET/CT imaging data compared to healthy controls. Further comparison was made in different prognostic groups categorized by modified Rankin Scale (mRS). RESULTS: In total, 24 patients (68.6%) were tested positive neuronal antibodies in serum and/or CSF. Psychiatric symptoms and seizure attacks were major clinical symptoms. In the acute stage, 13 patients (37.1%) demonstrated abnormal brain MRI results, while 33 (94.3%) presented abnormal metabolism patterns. 18F-FDG PET/CT was more sensitive than MRI (p < 0.05). Patients with AE mainly presented mixed metabolism patterns compared to the matched controls, demonstrating hypermetabolism mainly in the cerebellum, BG, MTL, brainstem, insula, middle frontal gyrus, and relatively hypometabolism in the frontal cortex, occipital cortex, temporal gyrus, right parietal gyrus, left cingulate gyrus (p < 0.05, FWE corrected). After a median follow-up of 26 months, the multivariable analysis identified a decreased level of consciousness as an independent risk factor associated with poor outcome of AE (HR = 3.591, p = 0.016). Meanwhile, decreased metabolism of right superior frontal gyrus along with increased metabolism of the middle and upper brainstem was more evident in patients with poor outcome (p < 0.001, uncorrected). CONCLUSION: 18F-FDG PET/CT was more sensitive than MRI to detect neuroimaging abnormalities of AE. A mixed metabolic pattern, characterized by large areas of cortical hypometabolism with focal hypermetabolism was a general metabolic pattern. Decreased metabolism of right superior frontal gyrus with increased metabolism of the middle and upper brainstem may predict poor long-term prognosis of AE.

Single-Atom 3d Transition Metals on SnO2 as Model Cell for Conversion Mechanism: Revealing Thermodynamic Catalytic Effects on Enhanced Na Storage of Heterostructures.

Since the discovery in 2000, conversion-type materials have emerged as a promising negative-electrode candidate for next-generation batteries with high capacity and tunable voltage, limited by low reversibility and severe voltage hysteresis. Heterogeneous construction stands out as a cost-effective and efficient approach to reducing reaction barriers and enhancing energy density. However, the second term introduced by conventional heterostructure inevitably complicates the electrochemical analysis and poses great challenges to harvesting systematic insights and theoretical guidance. A model cell is designed and established herein for the conversion reactions between Na and TMSA-SnO2, where TMSA-SnO2 represents single atom modification of eight different 3d transition elements (V, Cr, Mn, Fe, Co, Ni, Cu or Zn). Such a model unit fundamentally eliminates the interference from the second phase and thus enables independent exploration of activation manifestations of the heterogeneous architecture. For the first time, a thermodynamically dependent catalytic effect is proposed and verified through statistical data analysis. The mechanism behind the unveiled catalytic effect is further elucidated by which the active d orbitals of transition metals weaken the surface covalent bonds and lower the reaction barriers. This research provides both theoretical insights and practical demonstrations of the advanced heterogeneous electrodes.

Production of activated carbon from spent coffee grounds (SCG) for removal of hexavalent chromium from synthetic wastewater solutions.

In this research, spent coffee grounds (SCG) are converted into a highly valuable porous adsorbent which removes chromium (VI) from wastewater with high efficiency. A set of nine Spent Coffee Ground Activated Carbon (SCG-AC) adsorbent samples were synthesized, by varying key parameters including pyrolysis temperature (400, 600 °C), pyrolysis duration (1 and 2 h), and the impregnation ratio of the activating agent, KOH (ranging from 0:1 to 2:1). Characterizations of these adsorbent samples were conducted by advanced analytical tools including SEM, EDX, XRD, FTIR, TGA, and BET. Furthermore, we carried out adsorption studies, exploring the effects of temperature and dosage variations. Additionally, point zero charge experiments and desorption studies were carried out to further understand the adsorption process. The outcomes of our investigation demonstrate the successful synthesis of these spent coffee ground-derived adsorbents, with a yield of up to 34%. Notably, these adsorbents exhibited high efficiency in extracting chromium (VI) from water, with removal efficiencies ranging from 75% to 100%. The adsorption isotherms revealed the Langmuir model to be the most fitting descriptor of the adsorption behavior. Moreover, a thermodynamics study revealed the process to be endothermic in nature which furthers our understanding of the underlying mechanisms. Importantly, our cost assessment shows the economic advantage of the synthesized adsorbent over commercial counterparts such as zeolite, making it a competitive choice for real-world applications. In summation, the study not only introduces an innovative and sustainable utilization of spent coffee grounds but also delivers an in-depth exploration of the synthesized adsorbent's ability in chromium (VI) removal. Our holistic approach, encompassing thorough experimentation, characterization, and economic evaluation, solidifies the significance of this research in tackling environmental concerns and propelling advancements in wastewater treatment methodologies.

The consequences of using microlysimeters: Why microlysimeters grossly overestimate dew amounts in arid regions? A critical review.

Although commonly considered the gold standard for measurement of non-rainfall water (NRW), providing reasonable reliable data for vegetated soils, microlysimeters (MLs) tend to grossly overestimate NRW (primarily in form of dew) on barren soil. In arid and semiarid regions, the reported values may be overestimated by hundreds and even 1000 %. This bias is attributed to (i) the effect of the structure and dimension of the ML (ii) the tacit assumption that the weight difference between morning and the previous midday/evening results from dew or (iii) the belief that the MLs will provide reliable values if the difference in weight would be calculated only from the evening or night. For instance, from the time during which the air temperature reaches the dewpoint temperature or from the time during which condensation takes place on an adjacent leaf-wetness sensor. Calculating dew by the weight difference of MLs led to the notions that the fine-textured soil will necessarily promote higher values of dew, and the notion that higher amounts of dew are expected following days with low relative humidity, both of which hamper our understanding regarding dew formation. The reasons for the apparent different performance of MLs in vegetated (wet) and barren (arid) regions are discussed.

Association of lipid-lowering drugs with risk of sarcopenia: a drug target mendelian randomization study and meta-analysis.

BACKGROUND: Lipid-lowering drugs are widely used among the elderly, with some studies suggesting links to muscle-related symptoms. However, the causality remains uncertain. METHODS: Using the Mendelian randomization (MR) approach, we assessed the causal effects of genetically proxied reduced low-density lipoprotein cholesterol (LDL-C) through inhibitions of hydroxy-methyl-glutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and Niemann-Pick C1-like 1 (NPC1L1) on sarcopenia-related traits, including low hand grip strength, appendicular lean mass, and usual walking pace. A meta-analysis was conducted to combine the causal estimates from different consortiums. RESULTS: Using LDL-C pooled data predominantly from UK Biobank, genetically proxied inhibition of HMGCR was associated with higher appendicular lean mass (beta = 0.087, P = 7.56 × 10- 5) and slower walking pace (OR = 0.918, P = 6.06 × 10- 9). In contrast, inhibition of PCSK9 may reduce appendicular lean mass (beta = -0.050, P = 1.40 × 10- 3), while inhibition of NPC1L1 showed no causal impact on sarcopenia-related traits. These results were validated using LDL-C data from Global Lipids Genetics Consortium, indicating that HMGCR inhibition may increase appendicular lean mass (beta = 0.066, P = 2.17 × 10- 3) and decelerate walking pace (OR = 0.932, P = 1.43 × 10- 6), whereas PCSK9 inhibition could decrease appendicular lean mass (beta = -0.048, P = 1.69 × 10- 6). Meta-analysis further supported the robustness of these causal associations. CONCLUSIONS: Genetically proxied HMGCR inhibition may increase muscle mass but compromise muscle function, PCSK9 inhibition could result in reduced muscle mass, while NPC1L1 inhibition is not associated with sarcopenia-related traits and this class of drugs may serve as viable alternatives to sarcopenia individuals or those at an elevated risk.

Mechanisms of Action of the US Food and Drug Administration-Approved Antisense Oligonucleotide Drugs.

Antisense oligonucleotides (ASOs) are single stranded nucleic acids that target RNA. The US Food and Drug Administration has approved ASOs for several diseases. ASOs utilize three principal modes of action (MOA). The first MOA is initiated by base-pairing between the ASO and its target mRNA, followed by RNase H-dependent mRNA degradation. The second MOA is triggered by ASOs that occlude splice acceptor sites in pre-mRNAs leading to skipping of a mutation-bearing exon. The third MOA involves ASOs that sterically hinder mRNA function, often inhibiting translation. ASOs contain a variety of modifications to the sugar-phosphate backbone and bases that stabilize the ASO or render them resistant to RNase activity. RNase H-dependent ASOs include inotersen and eplontersen (for hereditary transthyretin amyloidosis), fomiversen (for opportunistic cytomegalovirus infection), mipomersen (for familial hypercholesterolemia), and tofersen [for amyotrophic lateral sclerosis (ALS)]. Splice modulating ASOs include nursinersen (for spinal muscular atrophy) and eteplirsen, golodirsen, viltolarsen, and casimersen (all for the treatment of Duchenne muscular dystrophy). In addition, a designer ASO, milasen, was used to treat a single individual afflicted with Batten disease. Since ASO design relies principally upon knowledge of mRNA sequence, the bench to bedside pipeline for ASOs is expedient compared with protein-directed drugs. [Graphical abstract available.].

PA200-Mediated Proteasomal Protein Degradation and Regulation of Cellular Senescence.

Cellular senescence is closely related to DNA damage, proteasome inactivity, histone loss, epigenetic alterations, and tumorigenesis. The mammalian proteasome activator PA200 (also referred to as PSME4) or its yeast ortholog Blm10 promotes the acetylation-dependent degradation of the core histones during transcription, DNA repair, and spermatogenesis. According to recent studies, PA200 plays an important role in senescence, probably because of its role in promoting the degradation of the core histones. Loss of PA200 or Blm10 is a major cause of the decrease in proteasome activity during senescence. In this paper, recent research progress on the association of PA200 with cellular senescence is summarized, and the potential of PA200 to serve as a therapeutic target in age-related diseases is discussed.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Gas-propelled nanomotors alleviate colitis through the regulation of intestinal immunoenvironment-hematopexis-microbiota circuits.

The progression of ulcerative colitis (UC) is associated with immunologic derangement, intestinal hemorrhage, and microbiota imbalance. While traditional medications mainly focus on mitigating inflammation, it remains challenging to address multiple symptoms. Here, a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO2 nanospheres with Cu2O nanoblocks. The resulting CaO2-Cu2O possessed a desirable diameter (291.3 nm) and a uniform size distribution. It could be efficiently internalized by colonic epithelial cells and macrophages, scavenge intracellular reactive oxygen/nitrogen species, and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 phenotype. This nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen bubbles. Rectal administration of CaO2-Cu2O could stanch the bleeding, repair the disrupted colonic epithelial layer, and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation, anti-oxidation, wound healing, and anti-inflammation. Impressively, it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria (e.g., Odoribacter and Bifidobacterium) and decreasing the abundances of harmful bacteria (e.g., Prevotellaceae and Helicobacter). Our gas-driven CaO2-Cu2O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

Design, synthesis, and anti-oomycete activity of 3-acyloxymaltol/ethyl maltol derivatives.

Twenty 3-acyloxymaltol/ethyl maltol derivatives (7a-j and 8a-j) were synthesized and evaluated in vitro for their anti-oomycete activity against Phytophthora capsici, respectively. Among all of twenty derivatives, more than half of the compounds 7f, 7h, 8a-h and 8j had anti-oomycete activity higher than the positive control zoxamide (EC50 = 22.23 mg/L), and the EC50 values of 18.66, 20.32, 12.80, 16.18, 10.59, 14.98, 16.80, 10.36, 15.32, 12.64, and 13.59 mg/L, respectively. Especially, compounds 8c and 8f exhibited the best anti-oomycete activity against P. capsici with EC50 values of 10.59 and 10.36 mg/L, respectively. Overall, hydroxyl group of maltol/ethyl maltol is important active modification site.

Temporal-spatial variability of grazing behaviors of yaks and the drivers of their intake on the eastern Qinghai-Tibetan Plateau.

Introduction: Grassland-livestock balance is an important principle of sustainable development of grassland livestock production and grassland ecosystem health. Grassland degradation becomes more serious at global scales and especially at the area that is sensitive to climate change and human activities. Decreases in pasture biomass and shifts in plant community composition in degraded grasslands can largely affect grazing behaviors of livestock. Up to date, however, it is unclear that whether livestock behaviors change across spatial and temporal scales and what key factors are to shape observed behavioral patterns of livestock. Methods: Here, yak behaviors including grazing, rumination and walking on the eastern Qinghai-Tibetan Plateau (QTP) were monitored by a continuous visual observation, to investigate temporal and spatial variations of grazing behavior of yaks (Bos grunniens); based on the data from public database in the past 18 years, a meta-analysis was conducted to examine the main factors that affect grazing behaviors and intake of yaks. Results: We showed that grazing behaviors of yaks differed significantly within hours, among hours of each day and among days as well as across different observation sites. Intake rate of yaks was higher in the morning than in the afternoon, but walking speed showed an inverse trend compared with intake rate. Resting, altitude, the mean annual precipitation (MAP), the mean annual temperature (MAT), forage ash, yak age and season were the main predictors for yak intake, and forage and yak individual characteristics had direct effects on grazing behaviors and intake of yaks. Discussion: The findings confirm that grazing behaviors of yaks can vary even at small temporal scales and regional scales, which is closely related to the shift in forage quality and biomass caused by environmental changes. The study suggests that multiple factors can be responsible for the variation in livestock behaviors and shifts in behavioral patterns may consequently lead to positive or negative feedback to grassland ecosystems through plant-animal interactions.

The Identification and Gene Mapping of Spotted Leaf Mutant spl43 in Rice.

Our study investigates the genetic mechanisms underlying the spotted leaf phenotype in rice, focusing on the spl43 mutant. This mutant is characterized by persistent reddish-brown leaf spots from the seedling stage to maturity, leading to extensive leaf necrosis. Using map-based cloning, we localized the responsible locus to a 330 Kb region on chromosome 2. We identified LOC_Os02g56000, named OsRPT5A, as the causative gene. A point mutation in OsRPT5A, substituting valine for glutamic acid, was identified as the critical factor for the phenotype. Functional complementation and the generation of CRISPR/Cas9-mediated knockout lines in the IR64 background confirmed the central role of OsRPT5A in controlling this trait. The qPCR results from different parts of the rice plant revealed that OsRPT5A is constitutively expressed across various tissues, with its subcellular localization unaffected by the mutation. Notably, we observed an abnormal accumulation of reactive oxygen species (ROS) in spl43 mutants by examining the physiological indexes of leaves, suggesting a disruption in the ROS system. Complementation studies indicated OsRPT5A's involvement in ROS homeostasis and catalase activity regulation. Moreover, the spl43 mutant exhibited enhanced resistance to Xanthomonas oryzae pv. oryzae (Xoo), highlighting OsRPT5A's role in rice pathogen resistance mechanisms. Overall, our results suggest that OsRPT5A plays a critical role in regulating ROS homeostasis and enhancing pathogen resistance in rice.

Global, regional, and national trends in metabolic risk factor-associated mortality among the working-age population from 1990-2019: An age-period-cohort analysis of the Global Burden of Disease 2019 study.

BACKGROUND: Metabolic diseases contribute significantly to premature mortality worldwide, with increasing burdens observed among the working-age population (WAP). This study assessed global, regional, and national trends in metabolic disorders and associated mortality over three decades in WAP. METHODS: Data from the Global Burden of Disease 2019 study were leveraged to assess global metabolism-associated mortality and six key metabolic risk factors in WAP from 1990-2019. An age-period-cohort model was employed to determine the overall percentage change in mortality. RESULTS: The 2019 global metabolic risk-related mortality rate in WAP rose significantly by 50.73%, while the age-standardized mortality rate declined by 21.5%. India, China, Indonesia, the USA, and the Russian Federation were the top contributing countries to mortality in WAP, accounting for 51.01% of the total. High systolic blood pressure (HSBP), high body mass index (HBMI), and high fasting plasma glucose (HFPG) were the top metabolic risk factors for the highest mortality rates. Adverse trends in HBMI-associated mortality were observed, particularly in lower sociodemographic index (SDI) regions. HFPG-related mortality declined globally but increased in older age groups in lower SDI countries. CONCLUSIONS: Despite a general decline in metabolic risk-related deaths in WAP, increasing HBMI- and HFPG-related mortality in lower SDI areas poses ongoing public health challenges. Developing nations should prioritize interventions addressing HBMI and HFPG to mitigate mortality risks in WAP.