Extracellular vesicles secreted by 3D tumor organoids are enriched for immune regulatory signaling biomolecules compared to conventional 2D glioblastoma cell systems.

Background: Newer 3D culturing approaches are a promising way to better mimic the in vivo tumor microenvironment and to study the interactions between the heterogeneous cell populations of glioblastoma multiforme. Like many other tumors, glioblastoma uses extracellular vesicles as an intercellular communication system to prepare surrounding tissue for invasive tumor growth. However, little is known about the effects of 3D culture on extracellular vesicles. The aim of this study was to comprehensively characterize extracellular vesicles in 3D organoid models and compare them to conventional 2D cell culture systems. Methods: Primary glioblastoma cells were cultured as 2D and 3D organoid models. Extracellular vesicles were obtained by precipitation and immunoaffinity, with the latter allowing targeted isolation of the CD9/CD63/CD81 vesicle subpopulation. Comprehensive vesicle characterization was performed and miRNA expression profiles were generated by smallRNA-sequencing. In silico analysis of differentially regulated miRNAs was performed to identify mRNA targets and corresponding signaling pathways. The tumor cell media and extracellular vesicle proteome were analyzed by high-resolution mass spectrometry. Results: We observed an increased concentration of extracellular vesicles in 3D organoid cultures. Differential gene expression analysis further revealed the regulation of twelve miRNAs in 3D tumor organoid cultures (with nine miRNAs down and three miRNAs upregulated). MiR-23a-3p, known to be involved in glioblastoma invasion, was significantly increased in 3D. MiR-7-5p, which counteracts glioblastoma malignancy, was significantly decreased. Moreover, we identified four miRNAs (miR-323a-3p, miR-382-5p, miR-370-3p, miR-134-5p) located within the DLK1-DIO3 domain, a cancer-associated genomic region, suggesting a possible importance of this region in glioblastoma progression. Overrepresentation analysis identified alterations of extracellular vesicle cargo in 3D organoids, including representation of several miRNA targets and proteins primarily implicated in the immune response. Conclusion: Our results show that 3D glioblastoma organoid models secrete extracellular vesicles with an altered cargo compared to corresponding conventional 2D cultures. Extracellular vesicles from 3D cultures were found to contain signaling molecules associated with the immune regulatory signaling pathways and as such could potentially change the surrounding microenvironment towards tumor progression and immunosuppressive conditions. These findings suggest the use of 3D glioblastoma models for further clinical biomarker studies as well as investigation of new therapeutic options.

Systematic review and network meta-analysis on the efficacy and safety of parmacotherapy for hand osteoarthritis.

OBJECTIVE: Hand osteoarthritis poses a significant health challenge globally due to its increasing prevalence and the substantial burden on individuals and the society. In current clinical practice, treatment options for hand osteoarthritis encompass a range of approaches, including biological agents, antimetabolic drugs, neuromuscular blockers, anti-inflammatory drugs, hormone medications, pain relievers, new synergistic drugs, and other medications. Despite the diverse array of treatments, determining the optimal regimen remains elusive. This study seeks to conduct a network meta-analysis to assess the effectiveness and safety of various drug intervention measures in the treatment of hand osteoarthritis. The findings aim to provide evidence-based support for the clinical management of hand osteoarthritis. METHODS: We performed a comprehensive search across PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials was conducted until September 15th, 2022, to identify relevant randomized controlled trials. After meticulous screening and data extraction, the Cochrane Handbook's risk of bias assessment tool was applied to evaluate study quality. Data synthesis was carried out using Stata 15.1 software. RESULTS: 21 studies with data for 3965 patients were meta-analyzed, involving 20 distinct Western medicine agents. GCSB-5, a specific herbal complex that mainly regulate pain in hand osteoarthritis, showed the greatest reduction in pain [WMD = -13.00, 95% CI (-26.69, 0.69)]. CRx-102, s specific medication characterized by its significant effect for relieving joint stiffness symptoms, remarkably mitigated stiffness [WMD = -7.50, 95% CI (-8.90, -6.10)]. Chondroitin sulfate displayed the highest incidence of adverse events [RR = 0.26, 95% CI (0.06, 1.22)]. No substantial variation in functional index for hand osteoarthritis score improvement was identified between distinct agents and placebo. CONCLUSIONS: In summary, GCSB-5 and CRx-102 exhibit efficacy in alleviating pain and stiffness in HOA, respectively. However, cautious interpretation of the results is advised. Tailored treatment decisions based on individual contexts are imperative.

Enlarged perivascular spaces in alcohol-related brain damage induced by dyslipidemia.

Perivascular spaces (PVSs) as the anatomical basis of the glymphatic system, are increasingly recognized as potential imaging biomarkers of neurological conditions. However, it is not clear whether enlarged PVSs are associated with alcohol-related brain damage (ARBD). We aimed to investigate the effect of long-term alcohol exposure on dyslipidemia and the glymphatic system in ARBD. We found that patients with ARBD exhibited significantly enlargement of PVSs in the frontal cortex and basal ganglia, as well as a notable increased levels of total cholesterol (TC) and triglycerides (TG). The anatomical changes of the glymphatic drainage system mentioned above were positively associated with TC and TG. To further explore whether enlarged PVSs affects the function of the glymphatic system in ARBD, we constructed long alcohol exposure and high fat diet mice models. The mouse model of long alcohol exposure exhibited increased levels of TC and TG, enlarged PVSs, the loss of aquaporin-4 polarity caused by reactive astrocytes and impaired glymphatic drainage function which ultimately caused cognitive deficits, in a similar way as high fat diet leading to impairment in glymphatic drainage. Our study highlights the contribution of dyslipidemia due to long-term alcohol abuse in the impairment of the glymphatic drainage system.

Self-Assembled Origami Neural Probes for Scalable, Multifunctional, Three-Dimensional Neural Interface.

Flexible intracortical neural probes have drawn attention for their enhanced longevity in high-resolution neural recordings due to reduced tissue reaction. However, the conventional monolithic fabrication approach has met significant challenges in: (i) scaling the number of recording sites for electrophysiology; (ii) integrating of other physiological sensing and modulation; and (iii) configuring into three-dimensional (3D) shapes for multi-sided electrode arrays. We report an innovative self-assembly technology that allows for implementing flexible origami neural probes as an effective alternative to overcome these challenges. By using magnetic-field-assisted hybrid self-assembly, multiple probes with various modalities can be stacked on top of each other with precise alignment. Using this approach, we demonstrated a multifunctional device with scalable high-density recording sites, dopamine sensors and a temperature sensor integrated on a single flexible probe. Simultaneous large-scale, high-spatial-resolution electrophysiology was demonstrated along with local temperature sensing and dopamine concentration monitoring. A high-density 3D origami probe was assembled by wrapping planar probes around a thin fiber in a diameter of 80∼105 µm using optimal foldable design and capillary force. Directional optogenetic modulation could be achieved with illumination from the neuron-sized micro-LEDs (µLEDs) integrated on the surface of 3D origami probes. We could identify angular heterogeneous single-unit signals and neural connectivity 360° surrounding the probe. The probe longevity was validated by chronic recordings of 64-channel stacked probes in behaving mice for up to 140 days. With the modular, customizable assembly technologies presented, we demonstrated a novel and highly flexible solution to accommodate multifunctional integration, channel scaling, and 3D array configuration.

The role of the paraspinal muscles in the development of adolescent idiopathic scoliosis based on surface electromyography and radiographic analysis.

BACKGROUND: Patients with idiopathic scoliosis commonly present with an imbalance of the paraspinal muscles. However, it is unclear whether this muscle imbalance is an underlying cause or a result of idiopathic scoliosis. This study aimed to investigate the role of paraspinal muscles in the development of idiopathic scoliosis based on surface electromyography (sEMG) and radiographic analyses. METHODS: This was a single-center prospective study of 27 patients with single-curve idiopathic scoliosis. Posteroanterior whole-spine radiographs and sEMG activity of the erector spinae muscles were obtained for all patients in the habitual standing position (HSP), relaxed prone position (RPP), and prone extension position (PEP). The Cobb angle, symmetrical index (SI) of the sEMG activity (convex/concave), and correlation between the two factors were analyzed. RESULTS: In the total cohort, the mean Cobb angle in the HSP was significantly greater than the mean Cobb angle in the RPP (RPP-Cobb) (p < 0.001), whereas the mean Cobb angle in the PEP (PEP-Cobb) did not differ from the RPP-Cobb. Thirteen patients had a PEP-Cobb that was significantly smaller than their RPP-Cobb (p = 0.007), while 14 patients had a PEP-Cobb that was significantly larger than their RPP-Cobb (p < 0.001). In the total cohort and two subgroups, the SI of sEMG activity at the apex vertebra (AVSI) in the PEP was significantly greater than 1, revealing significant asymmetry, and was also significantly larger than the AVSI in the RPP. In the RPP, the AVSI was close to 1 in the total cohort and two subgroups, revealing no significant asymmetry. CONCLUSION: The coronal Cobb angle and the SI of paraspinal muscle activity in AIS patients vary with posture changes. Asymmetrical sEMG activity of the paraspinal muscles may be not an inherent feature of AIS patients, but is evident in the challenging tasks. The potential significance of asymmetric paraspinal muscle activity need to be explored in further research.

Fabrication and Application of Ag@SiO2/Au Core-Shell SERS Composite in Detecting Cu2+ in Water Environment.

A sensitive and simple method for detecting Cu2+ in the water source was proposed by using surface-enhanced Raman scattering spectroscopy (SERS) based on the Ag@SiO2/Au core-shell composite. The Ag@SiO2 SERS tag was synthesized by a simple approach, in which Ag nanoparticles were first embedded with Raman reporter PATP and next coated with a SiO2 shell. The Ag@SiO2 nanoparticles had strong stability even in a high-concentration salty solution, and there were no changes to their properties and appearance within one month. The Ag@SiO2/Au composite was fabricated through a controllable self-assemble process. L-cysteine was decorated on the surface of a functionalized Ag@SiO2/Au composite, as the amino and carboxyl groups of it can form coordinate covalent bond with Cu2+, which shows that the Ag@SiO2/Au composite labelled with L-cysteine has excellent performance for the detection of Cu2+ in aqueous media. In this study, the SERS detection of Cu2+ was carried out using Ag@SiO2 nanoparticles, and the limit of detection (LOD) as low as 0.1 mg/L was achieved.

High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia.

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia (ITP), this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight (CyTOF). Thirty-six patients with ITP and nine healthy volunteers were enrolled in the study. As soluble immunomodulatory molecules, more sCD25 and sGalectin-9 were detected in ITP patients. On the cell surface, co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells. In contrast, co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets. Taking a platelet count of 30×109 L-1 as the cutoff value, ITP patients with high and low platelet counts showed different T cell immune profiles. Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions, respectively, and participate in the pathogenesis of ITP. In conclusion, the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP. They may offer novel targets to develop personalized immunotherapies.

Exploring the role of biotic factors in regulating the spatial variability in land surface phenology across four temperate forest sites.

Land surface phenology (LSP), the characterization of plant phenology with satellite data, is essential for understanding the effects of climate change on ecosystem functions. Considerable LSP variation is observed within local landscapes, and the role of biotic factors in regulating such variation remains underexplored. In this study, we selected four National Ecological Observatory Network terrestrial sites with minor topographic relief to investigate how biotic factors regulate intra-site LSP variability. We utilized plant functional type (PFT) maps, functional traits, and LSP data to assess the explanatory power of biotic factors for the start and end of season (SOS and EOS) variability. Our results indicate that PFTs alone explain only 0.8-23.4% of intra-site SOS and EOS variation, whereas including functional traits significantly improves explanatory power, with cross-validation correlations ranging from 0.50 to 0.85. While functional traits exhibited diverse effects on SOS and EOS across different sites, traits related to competitive ability and productivity were important for explaining both SOS and EOS variation at these sites. These findings reveal that plants exhibit diverse phenological responses to comparable environmental conditions, and functional traits significantly contribute to intra-site LSP variability, highlighting the importance of intrinsic biotic properties in regulating plant phenology.

The Impact of Social Vulnerability on Alcohol Consumption and Mortality: A 20-year Age, Sex-stratified Analysis From the Taiwan Longitudinal Study of Aging.

OBJECTIVE: This study aimed to use the Social Vulnerability Index (SVI) to encapsulate the complex and multidimensional nature of social determinants and their influence on alcohol intake and mortality in middle-aged and older individuals. DESIGN: Cohort study. SETTING AND PARTICIPANTS: Data were obtained from the Taiwan Longitudinal Study on Aging (TLSA), with 3945 study participants aged 50 years and older. METHODS: The TLSA questionnaire defined SVI (51 items including living conditions, social support, socially oriented activities of daily living, social engagement and leisure, empowerment of life, satisfaction about life, and socioeconomic status) and alcohol intake (behavior as well as type and frequency of alcohol intake). Multivariate Cox proportional hazard models were used to estimate the association between alcohol intake and mortality, stratified by gender and SVI groups. RESULTS: Men with high social vulnerability and high alcohol intake exhibit an elevated mortality risk (adjusted hazard ratio [aHR], 1.51; 95% CI, 1.01-2.24), whereas notably, women in similar social circumstances but with moderate alcohol intake face a quintupled mortality risk (>35 g/wk; aHR, 5.67; 95% CI, 2.37-13.61). The impact of alcohol and social vulnerability on mortality was more pronounced in men younger than 65. Among them, those with high social vulnerability and moderate (35-140 g/wk; aHR, 2.83; 95% CI, 1.50-5.36) to high (>140 g/wk; aHR, 2.24; 95% CI, 1.15-4.35) alcohol intake was associated with an increased risk of mortality. CONCLUSIONS AND IMPLICATIONS: Various factors throughout the life course of both men and women significantly impact the risk of all-cause mortality due to alcohol intake, underscoring the importance of social vulnerability as a determinant of both alcohol intake behavior and mortality risk.

HSFA3 functions as a positive regulator of HSFA2a to enhance thermotolerance in perennial ryegrass.

Perennial ryegrass (Lolium perenne) is a widely used cool season turfgrass with outstanding turf quality and grazing tolerance. High temperature is the key factor restricting the distribution of perennial ryegrass in temperate and sub-tropic regions. In this study, we found that one HEAT SHCOK TRANSCRIPTION FACOTR (HSF) class A gene from perennial ryegrass, LpHSFA3, was highly induced by heat stress. LpHSFA3 is localized in nucleus and functions as a transcription factor. Ectopic overexpression of LpHSFA3 in Arabidopsis improved thermotolerance and rescued heat sensitive deficiency of athsfa3 mutant. Overexpression of LpHSFA3 in perennial ryegrass enhanced heat tolerance and increased survival rate in summer season as evidenced by decreased EL and MDA, increased number of green leaves and total chlorophyll content. LpHSFA3 binds to the HSE region in LpHSFA2a promoter to constitutively activate the expression of LpHSFA2a and downstream heat stress responsive genes. Ectopic overexpression of LpHSFA2a consequently rescued thermal sensitivity of athsfa3 mutant and enhanced thermotolerance of athsfa2 mutant. Perennial ryegrass protoplasts with overexpression of LpHSFA3 and LpHSFA2a exhibited induction of similar subsets of heat responsive genes. These results indicated that transcription factor LpHSFA3 functions as positive regulator of LpHSFA2a to improve thermotolerance of perennial ryegrass, providing further evidence to understand the regulatory networks of plant heat stress response.

Implementing virtual reality technology to teach medical college systemic anatomy: A pilot study.

It can be difficult for some students to learn three-dimensional anatomical structure concepts. While virtual reality (VR) systems have been reported as helpful for learning, there has been scarce research on either VR teaching strategies or the influence of visually induced motion sickness (VIMS) in the context of large anatomy classes (i.e., over 100 students). The study thus aimed to (1) establish a VR anatomy instruction video for a large class; (2) determine how many students experience VIMS when watching a VR anatomy instruction video; (3) evaluate the influence of VIMS on VR anatomy video-based learning; and (4) examine whether a small screen size alleviates VIMS. Laboratory course students viewing a VR anatomy instruction video about the vascular system were invited to participate in the questionnaire survey. Anatomy faculty and staff participated in an experimental trial to determine whether small screen size could alleviate VIMS. The Likert scale survey revealed that students reported the VR strategy as advantageous and appropriate for large classes, but that it cannot replace practical dissection. Of the total participants, 32% reported experiencing VIMS, and 40% of those experiencing VIMS agreed that this could negatively impact their learning through a VR anatomy instruction video. Adjusting the screen size from large to small significantly delayed the onset of VIMS. In conclusion, the VR anatomy instruction video strategy is feasible and helpful for large classes, but educators should consider VIMS when planning their use of this teaching approach.

Inertial Measuring System to Evaluate Gait Parameters and Dynamic Alignments for Lower-Limb Amputation Subjects.

The study aims to construct an inertial measuring system for the application of amputee subjects wearing a prosthesis. A new computation scheme to process inertial data by installing seven wireless inertial sensors on the lower limbs was implemented and validated by comparing it with an optical motion capture system. We applied this system to amputees to verify its performance for gait analysis. The gait parameters are evaluated to objectively assess the amputees' prosthesis-wearing status. The Madgwick algorithm was used in the study to correct the angular velocity deviation using acceleration data and convert it to quaternion. Further, the zero-velocity update method was applied to reconstruct patients' walking trajectories. The combination of computed walking trajectory with pelvic and lower limb joint motion enables sketching the details of motion via a stickman that helps visualize and animate the walk and gait of a test subject. Five participants with above-knee (n = 2) and below-knee (n = 3) amputations were recruited for gait analysis. Kinematic parameters were evaluated during a walking test to assess joint alignment and overall gait characteristics. Our findings support the feasibility of employing simple algorithms to achieve accurate and precise joint angle estimation and gait parameters based on wireless inertial sensor data.

Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Slow-wave sleep and REM sleep without atonia predict motor progression in Parkinson's disease.

BACKGROUND: Growing evidence supports the potential role of sleep in the motor progression of Parkinson's disease (PD). Slow-wave sleep (SWS) and rapid eye movement (REM) sleep without atonia (RWA) are important sleep parameters. The association between SWS and RWA with PD motor progression and their predictive value have not yet been elucidated. METHODS: We retro-prospectively analyzed clinical and polysomnographic data of 136 patients with PD. The motor symptoms were assessed using Unified Parkinson's Disease Rating Scale Part III (UPDRS III) at baseline and follow-up to determine its progression. Partial correlation analysis was used to explore the cross-sectional associations between slow-wave energy (SWE), RWA and clinical symptoms. Longitudinal analyses were performed using Cox regression and linear mixed-effects models. RESULTS: Among 136 PD participants, cross-sectional partial correlation analysis showed SWE decreased with the prolongation of the disease course (P = 0.046), RWA density was positively correlated with Hoehn & Yahr (H-Y) stage (tonic RWA, P < 0.001; phasic RWA, P = 0.002). Cox regression analysis confirmed that low SWE (HR = 1.739, 95% CI = 1.038-2.914; P = 0.036; FDR-P = 0.036) and high tonic RWA (HR = 0.575, 95% CI = 0.343-0.963; P = 0.032; FDR-P = 0.036) were predictors of motor symptom progression. Furthermore, we found that lower SWE predicted faster rate of axial motor progression (P < 0.001; FDR-P < 0.001) while higher tonic RWA density was associated with faster rate of rigidity progression (P = 0.006; FDR-P = 0.024) using linear mixed-effects models. CONCLUSIONS: These findings suggest that SWS and RWA might represent markers of different motor subtypes progression in PD.

Application of magnetic resonance imaging radiomics in endometrial cancer: a systematic review and meta-analysis.

PURPOSE: We aimed to systematically assess the methodological quality and clinical potential application of published magnetic resonance imaging (MRI)-based radiomics studies about endometrial cancer (EC). METHODS: Studies of EC radiomics analyses published between 1 January 2000 and 19 March 2023 were extracted, and their methodological quality was evaluated using the radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Pairwise correlation analyses and separate meta-analyses of studies exploring differential diagnoses and risk prediction were also performed. RESULTS: Forty-five studies involving 3 aims were included. The mean RQS was 13.77 (range: 9-22.5); publication bias was observed in the areas of 'index test' and 'flow and timing'. A high RQS was significantly associated with therapy selection-aimed studies, low QUADAS-2 risk, recent publication year, and high-performance metrics. Raw data from 6 differential diagnosis and 34 risk prediction models were subjected to meta-analysis, revealing diagnostic odds ratios of 23.81 (95% confidence interval [CI] 8.48-66.83) and 18.23 (95% CI 13.68-24.29), respectively. CONCLUSION: The methodological quality of radiomics studies involving patients with EC is unsatisfactory. However, MRI-based radiomics analyses showed promising utility in terms of differential diagnosis and risk prediction.

Multiple geriatric syndromes in community-dwelling older adults in China.

This study aims to assess the prevalence of geriatric syndromes and identify factors associated with multiple geriatric syndromes in community-dwelling older adults in China. We utilized a convenience sampling method to recruit older adults and from one rural and one urban community in Chengdu, China, from October 2022 to March 2023. A total of 706 older adults aged 60 years or older were included. Ten geriatric syndromes were investigated including two mental disorders: depressive symptoms, cognitive impairment; and eight somatic disorders: pain, falls, sleep disturbance, constipation, polypharmacy, multimorbidity, malnutrition and frailty. Multiple geriatric syndromes were defined as an individual having two or more geriatric syndromes. The data obtained were analysed using descriptive statistics. The independent risk factors for multiple geriatric syndromes were assessed using a logistic regression model. This study found that 90.5% of the participants had at least one geriatric syndrome, with 72.8% experiencing multiple geriatric syndromes. The top four geriatric syndromes in our study were polypharmacy (58.5%), malnutrition/at risk of malnutrition (43.1%), multimorbidity (42.1%), and frailty/prefrailty (34.3%). Of the older adults, 368(52.1%) had only somatic disorders, 18(2.5%) had only mental disorders and 253 (35.8%) had somatic-mental disorders. According to the logistic regression analysis, residence, age, marriage, BMI, and self-related health were significantly associated with multiple geriatric syndromes among older adults. This study highlights that multiple geriatric syndromes are prevalent among community-dwelling older adults in China, and underscores the significance of certain demographic factors in their occurrence. Future longitudinal studies are needed to establish the temporal relationship between multiple geriatric syndromes and these demographic factors, as well as to explore causal relationships and effective prevention strategies for geriatric syndrome.

Unraveling crop enzymatic browning through integrated omics.

Enzymatic browning reactions, triggered by oxidative stress, significantly compromise the quality of harvested crops during postharvest handling. This has profound implications for the agricultural industry. Recent advances have employed a systematic, multi-omics approach to developing anti-browning treatments, thereby enhancing our understanding of the resistance mechanisms in harvested crops. This review illuminates the current multi-omics strategies, including transcriptomic, proteomic, and metabolomic methods, to elucidate the molecular mechanisms underlying browning. These strategies are pivotal for identifying potential metabolic markers or pathways that could mitigate browning in postharvest systems.

A Novel Air-Cooled Nd:YAG Laser for the Treatment of the Venous Lakes of the Lips.

Objective: To evaluate the therapeutic effect of a novel air-cooled Nd:YAG laser in the venous lakes of the lips (VLL). Background: The thermal injury is one of the most important issues during laser therapy for venous lakes. Methods: Six pieces of fresh pork livers were used to provide 30 regions with a diameter of 6 mm for experiment in vitro, among which 15 regions were treated by Nd:YAG laser with air cooling until the tissue turned gray-white, whereas the rest were treated without air cooling as control. The operation time of laser irradiation, the degree of temperature increase, and the depth of coagulation tissue were compared between two groups. Then, 60 VLL patients were selected for Nd:YAG laser treatment with or without air cooling. The operation time of laser irradiation, the degree of temperature increase, the postoperative pain visual analog scale (VAS) score, and the percentage of lesions removed within 1 month were compared. Results: In tissue studies, the treated group showed a longer operation time of laser irradiation (p < 0.01), a lower degree of temperature increase (p < 0.01), and there was no significant statistical difference in the depth of coagulation tissue (p = 0.624). In clinical studies, the treated group showed a longer operation time of laser irradiation (p < 0.01), a lower degree of temperature increase (p < 0.01), and a lower VAS score on the 1st and 2nd day, compared with the control group (p < 0.01). Conclusions: Air cooling during Nd:YAG laser for the treatment of VLL can prolong the surgical time, but lowered tissue temperature and reduced patient pain within 2 days under the premise of ensuring the treatment effect.

Spatial epidemiological analysis of the burden of liver cancer in China.

Background: Liver cancer is one of the most common cancers in the world, with unique regional variations in disability-adjusted life years (DALY) rate, nearly 50% of liver cancer cases occur in China. Therefore, understanding the epidemiological characteristics of liver cancer is of utmost importance. In this study, to analyze the spatial distribution characteristics and clustering of the DALY rate of liver cancer in 1990 and 2017 in China based on provincial administrative divisions, and to explore its possible influencing factor. Methods: The DALY rate data of liver cancer at the provincial level in China were collected, the global autocorrelation of the DALY rate was analyzed by Moran's I, the local autocorrelation of the DALY rate was analyzed by Getis-Ord-Gi*, and the influencing factors related to the DALY rate were analyzed by the least squares regression model. Results: The DALY rate of liver cancer in China generally showed an increasing trend. The DALY rate increased in 22 provinces and decreased in nine provinces. In 2017, the distribution of DALY rate in all provinces showed heterogeneity, with the highest DALY rate in Guangxi (1,363.37/100,000) and the lowest in Beijing (315.78/100,000). In 2017, the low and low clustering were mainly concentrated in Inner Mongolia, Ningxia, Shanxi, Hebei, and Tianjin. The low and high clustering in Yunnan, Guizhou, and Guangdong, were surrounded by the high clustering in neighboring provinces, high and high concentration is mainly concentrated in Hunan and neighboring provinces. The results of the least square regression model showed that the per capita years of education, hepatitis B incidence and the proportion of population over 65 years old had an impact on the DALY rate of liver cancer (P<0.05). Conclusions: The DALY rate of liver cancer in China showed an overall increasing trend. In 2017, the DALY rate of liver cancer in China had a spatial aggregation in the whole country, and the per capita years of education, the incidence of hepatitis B and the proportion of population over 65 years old had an impact on the DALY rate of liver cancer in space.

Tulip transcription factor TgWRKY75 activates salicylic acid and abscisic acid biosynthesis to synergistically promote petal senescence.

WRKY transcription factors play a central role in controlling plant organ senescence; however, it is unclear whether and how they regulate petal senescence in the widely grown ornamental plant tulip (Tulipa gesneriana). In this study, we report that TgWRKY75 promotes petal senescence by enhancing the synthesis of both abscisic acid (ABA) and salicylic acid (SA) in tulip and in transgenic Arabidopsis. The expression level of TgWRKY75 was up-regulated in senescent petals, and exogenous ABA or SA treatment induced its expression. The endogenous contents of ABA and SA significantly increased during petal senescence and in response to TgWRKY75 overexpression. Two SA synthesis-related genes, TgICS1 and TgPAL1, were identified as direct targets of TgWRKY75, which binds to their promoters. In parallel, TgWRKY75 activated the expression of the ABA biosynthesis-related gene TgNCED3 via directly binding to its promoter region. Site mutation of the W-box core motif located in the promoters of TgICS1, TgPAL1, and TgNCED3 eliminated their interactions with TgWRKY75. In summary, our study demonstrates a dual regulation of ABA and SA biosynthesis by TgWRKY75, revealing a synergistic process of tulip petal senescence through feedback regulation between TgWRKY75 and the accumulation of ABA and SA.