Gentiopicrin-Loaded Chitosan Nanoparticles as a Topical Agent for the Treatment of Psoriasis.

Psoriasis, a chronic inflammatory skin disease induced by various factors, including genetic factors, immune factors, environmental factors, and psychological factors, is characterized by thickening of the epidermis, excessive proliferation of keratinocytes, abnormal differentiation, and an excessive inflammatory response. Traditional treatments for psoriasis still face challenges because of limited curative effects, notable side effects, and a tendency for recurrence. In contrast, topical therapy provides a favorable option for psoriasis treatment because of its noninvasive and self-administered method. In this study, gentiopicrin (Gen) is encapsulated in the liposomes to form a nanodrug, and then chitosan is covered on the nanodrug to assemble the nanodrug delivery system (CS@Gen), which is used as a topical agent for treating psoriasis. Then M5 (a mixture of five pro-inflammatory cytokines, i.e., IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α)-induced HacaT cells and imiquimod-induced psoriasis mouse models are established, whose results show that CS@Gen induces apoptosis and inhibits the proliferation and cell migration of psoriasis keratinocytes. Additionally, the application of CS@Gen cream can significantly reduce epidermal thickness, diminish skin scaling, and improve other related mechanisms in mice affected by psoriasis. Meanwhile, the prepared CS@Gen can significantly reduce the expression levels of IL-17a, Cxcl2, S100a, Mki67, and other related inflammatory factors, resulting in indirectly inhibiting the inflammation of keratinocytes. In summary, the present study provides an ideal loading for an anti-inflammatory and immunomodulatory drug delivery system for the treatment of psoriasis.

[Source and Cause Analysis of High Concentration of Inorganic Aerosol During Two Typical Pollution Processes in Winter over Tianjin].

Inorganic aerosol is the main component of haze days in winter over Tianjin. In this study, two typical high concentrations of secondary inorganic aerosol (SIA) processes, defined as CASE1 and CASE2, were selected during polluted days in January 2020 over Tianjin, and the effects of meteorological factors, regional transport, and chemical processes were comprehensively investigated combined with observations and numerical models (WRF-NAQPMS). The average SIA concentrations in CASE1 and CASE2 were 76.8 µg·m-3 and 66.0 µg·m-3, respectively, and the nitrate concentration was higher than that of sulfate and ammonium, which were typical nitrate-dominated pollution processes. Meteorological conditions played a role in inorganic aerosol formation. The temperature of approximately -6-0℃ and 2-4℃ and the relative humidity of 50%-60% and 80%-100% would be suitable conditions for the high SIA concentration (>80 µg·m-3) in CASE1, whereas the temperature of approximately 2-4℃ and the relative humidity of 60%-70% would be suitable in CASE2. The average contribution rates of external sources to SIA in the CASE1 and CASE2 processes were 62.3% and 22.1%, which were regional transport-dominant processes and local emission-dominant processes, respectively. The contribution of the local emission of CASE1 to nitrate and sulfate was 16.2 µg·m-3 and 8.2 µg·m-3, respectively, higher than that of external sources (31.7 µg·m-3 and 8.8 µg·m-3). the local contribution of CASE2 to nitrate and sulfate was 29.3 µg·m-3 and 25.1 µg·m-3, respectively, whereas the contribution from external sources was 8.1 µg·m-3 and 9.4 µg·m-3, respectively. The quantitative result indicated that local formation and regional transport resulted in higher nitrate concentration than sulfate in CASE1, in contrast to only local sources in CASE2. The gas phase reaction was the main source of inorganic aerosol formation, contributing 48.9% and 57.8% in CASE1 and CASE2, respectively, whereas the heterogeneous reactions were also important processes, with contribution rates of 48.1% and 42.2% to SIA. The effect of aqueous phase reaction was negligible.

Effects of warming on rice production and metabolism process associated with greenhouse gas emissions.

Evaluating the impact of global warming on rice production and greenhouse gas (GHG) emissions is critical for ensuring food security and mitigating the consequences of climate change. Nonetheless, the impacts of warming on crop production, GHG emissions, and microbial mechanisms in the single-cropping rice systems remain unclear. Here, a two-year field experiment was conducted to explore the effects of warming (increased by 2.7-3.0 °C on average) in the rice growing season on crop production and functional microorganisms associated with GHG emissions. Results showed that warming resulted in significant reduction (p < 0.01) in the aboveground biomass and grain yield as well as in grain weight, the number of spikelets per panicle, and the seed-setting rate. However, it caused a significant increase (p < 0.01) in the number of panicles by 15.6 % and 34.9 %, respectively. Furthermore, warming significantly increased (p < 0.01) seasonal methane (CH4) emissions but reduced nitrous oxide (N2O) emissions, particularly in 2022.The relative abundance of genes associated with CH4 metabolism and nitrogen metabolism was increased by 40.7 % and 32.7 %, respectively, in response to warming. Moreover, warming had a positive impact on the abundance of genes related to CH4 production and oxidation processes but did not affect the denitrification processes associated with N2O production. These results showed that warming decreased rice yield and biomass in the single cropping rice system but increased CH4 emissions and global warming potential. Taken together, to address the increasing food demand of a growing population and mitigate the impacts of global warming, it is imperative to duce GHG emissions and enhance crop yields.

Association between hyperuricemia and ultrasound-detected hand synovitis.

OBJECTIVE: Although hand synovitis is prevalent in the older population, the aetiology remains unclear. Hyperuricemia, a modifiable metabolic disorder, may serve as an underlying mechanism of hand synovitis, but little is known about their relationship. We assessed the association between hyperuricemia and hand synovitis in a large population-based sample. METHODS: We performed a cross-sectional study in Longshan County, Hunan Province, China. Hyperuricemia was defined as a serum urate >420 µmol/L in men and >360 µmol/L in women. Ultrasound examinations were performed on both hands of 4,080 participants, and both grey-scale synovitis and Power Doppler signal (PDS) were assessed using semiquantitative scores (grades 0-3). We evaluated the association of hyperuricemia with hand grey-scale synovitis (grade ≥2) and PDS (grade ≥1), respectively, adjusting for age, sex and body mass index. RESULTS: All required assessments for analysis were available on 3,286 participants. The prevalence of hand grey-scale synovitis was higher among participants with hyperuricemia (30.0%) than those with normouricemia (23.3%), with an adjusted odds ratio (aOR) of 1.28 (95% confidence interval [CI]:1.00-1.62). Participants with hyperuricemia also had higher prevalence of PDS (aOR=2.36, 95% CI:1.15-4.81). Furthermore, hyperuricemia positively associated, both at the hand and joint levels, with presence of grey-scale synovitis (aOR=1.27, 95% CI:1.00-1.60, and adjusted prevalence ratio [aPR]=1.26, 95% CI:1.10-1.44, respectively), and PDS (aOR=2.35, 95% CI:1.15-4.79, and aPR=2.34, 95% CI:1.28-4.30, respectively). CONCLUSION: This population-based study provides more evidences for a positive association between hyperuricemia and prevalent hand synovitis.

Comparison of three concentrations of ropivacaine in posterior quadratus lumborum block: A randomized clinical trial.

Background: A conclusive evidence regarding the optimal concentration and volume of local anesthetic for quadratus lumborum block is lacking. Methods: In this single-center, prospective, randomized, controlled study, 60 patients scheduled for laparoscopic colorectal surgery were randomly assigned to 3 different combinations of volume and concentration of ropivacaine (3 mg/kg) - Group 0.25%, Group 0.375% and Group 0.5%. All subjects received ultrasound-guided posterior quadratus lumborum block prior to the induction. The primary outcome was the complete sensory block rate of surgical site measured at 30 min after quadratus lumborum block, after extubation, at 12, 24, and 48 h after operation. Secondary outcomes were the changes in hemodynamic parameters before and after incision (ΔSBP, ΔDBP and ΔHR), postoperative pain score, the sufentanil consumption after surgery, length of stay and adverse reactions. Results: The sensory block rate of surgical site at 5 time points differed significantly among the three groups (P < 0.001). Both Group 0.375% (P < 0.001) and Group 0.5% (P < 0.001) had a higher sensory block rate than Group 0.25%, but no significant difference was observed between the former two. Group 0.375% and Group 0.5% had lower postoperative pain scores, lower sufentanil consumption after surgery and shorter length of stay. No statistical difference was observed in ΔSBP, ΔDBP, ΔHR and the incidence of adverse reactions. Conclusions: 0.375% and 0.5% ropivacaine in posterior quadratus lumborum block provide better sensory block of surgical site when compared to 0.25% in laparoscopic colorectal surgery. Trial registration number: Chinese Clinical Trials Registry (ChiCTR2100043949).

Corrigendum: A metagenomic analysis of mosquito virome collected from different animal farms at Yunnan-Myanmar border of China.

[This corrects the article DOI: 10.3389/fmicb.2020.591478.].

In situ calibration of shear ratio for quadriwave lateral shearing interferometry using double-slit interference.

A new method, to the best of our knowledge, based on double-slit (DS) interference is proposed to accurately estimate the shear ratio of the system, with plane wave or spherical wave incidence. Existing shear ratio calibration methods, designed primarily for lateral shearing interferometry (LSI) with plane wave incidence, are not applicable to LSIs directly testing divergent or convergent spherical waves. Equations for calculating the shear ratio using the fringe spacing of the DS interferogram and the NA of the incident spherical wave are derived in this paper. The simulation result shows that the relative error of the shear ratio value is about 0.3%, when the shear ratio is 0.1. In the experiment, the quadriwave LSI is designed with a plug-in feature. The shear ratio at integer multiples of 1/6 Talbot distance from the modified Hartmann mask was calibrated using a DS, and the results were in good agreement with theoretical values, confirming the accuracy of the method. Subsequently, with the assistance of an inductance micrometer, the shear ratio was calibrated at intervals of 0.5 mm, and the results closely matched the theoretical variation of the shear ratio caused by displacement, confirming the high precision of the method.

Vaporization phosphorization-mediated synthesis of phosphorus-doped TiO2 nanocomposites for combined photodynamic and photothermal therapy of renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a disease with high incidence and poor prognosis. The conventional treatment involves radiotherapy and chemotherapy, but chemotherapeutic agents are often associated with side effects, i.e., cytotoxicity to nontumor cells. Therefore, there is an urgent need for the development of novel therapeutic strategies for ccRCC. We synthesized spherical P/TiO2 nanoparticles (P/TiO2 NPs) by vaporization phosphorization (VP). X-ray photoelectron spectroscopy (XPS) and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS) analyses confirmed that the anatase TiO2 surface was successfully doped with phosphorus and produced a large number of oxygen vacancies (OV). Serving as a photosensitizer, P/TiO2 NPs not only extended the photoresponse range to the near-infrared II region (NIR II) but also introduced a donor energy level lower than the TiO2 conduction band, narrowing the band gap, which could facilitate the migration of photogenerated charges and trigger the synergistic treatment of photodynamic therapy (PDT) and photothermal therapy (PTT). During NIR irradiation in vitro, the P/TiO2 NPs generated local heat and various oxygen radicals, including 1O2, ˙O2-, H2O2, and ˙OH, which damaged the ccRCC cells. In vivo, administration of the P/TiO2 NPs + NIR reduced the tumor volume by 80%, and had the potential to inhibit tumor metastasis by suppressing intratumor neoangiogenesis. The P/TiO2 NPs showed superior safety and efficacy relative to the conventional chemotherapeutic agent used in ccRCC treatment. This study introduced an innovative paradigm for renal cancer treatment, highlighting the potential of P/TiO2 NPs as safe and effective nanomaterials and presenting a compelling new option for clinical applications in anticancer therapy.

Exogenous application of ascorbic acid improves physiological and productive traits of Nigella sativa.

For thousands of years, plants have been utilized for medicinal purposes. For its naturally existing antibacterial properties, Nigella sativa is one of the most researched herbs. A study was conducted during rabi 2020-21 at The University of Haripur in order to evaluate the potential of ascorbic acid as plant growth enhancer. Two concentrations of ascorbic acid i-e 350 µm and 400 µm were sprayed along with control and water only spray on Nigella sativa crop. The study was arranged in RCBD two factor factorial arrangement. Factor A: ascorbic acid concentrations along with control and water spray, factor B: Growth stages (Stage1 = 40 days after sowing, Stage 2 = 80 DAS, Stage 3 = 120 DAS, Stage 4 = 40 + 80 DAS, Stage 5 = 40 + 120 DAS, Stage 6 = 80 + 120 DAS, Stage 7 = 40 + 80 + 120 DAS). Crop was sown in first week of November. Results reviled that chlorophyll b content, fixed oil content, 1000 seed weight, grain yield, Photosynthetic rate (µ mole m-2s-1), Transpiration rate (mmole m-2s-1), photosynthetic water use efficiency, Internal CO2 concentration (Ci) of leaf tissue and Stomatal conductance (mmole m-2s-1) were significantly affected by ascorbic acid concentrations and stage of application. Crop growth rate increased by 19.88% and 17.29%, chlorophyll b by 12.3% and 11.2%, fixed oil by 11.7% and 9%, grain yield by 10.29% and 9.8%, harvest index by 4% and 5.7% photosynthetic rate by 33%, 20% and stomatal conductance by 24.24% and 24.25 with application of ascorbic acid @ 350 µm, over control and water spray respectively. On the basis of these results it is concluded that application of ascorbic acid at the rate of 350 µm, followed by ascorbic acid at the rate of 400 µm significantly improves black cumin (Nigella sativa) yield and production. Hence it is recommended to apply ascorbic acid at the rate of 350 µm at 40 + 80+120 days after sowing of Nigella sativa crop for obtaining maximum results.

Efficacy and safety of perioperative therapy for locally resectable gastric cancer: A network meta-analysis of randomized clinical trials.

BACKGROUND: Gastric cancer (GC) is the fifth most commonly diagnosed malignancy worldwide, with over 1 million new cases per year, and the third leading cause of cancer-related death. AIM: To determine the optimal perioperative treatment regimen for patients with locally resectable GC. METHODS: A comprehensive literature search was conducted, focusing on phase II/III randomized controlled trials (RCTs) assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC. The R0 resection rate, overall survival (OS), disease-free survival (DFS), and incidence of grade 3 or higher nonsurgical severe adverse events (SAEs) associated with various perioperative regimens were analyzed. A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy. RESULTS: Thirty RCTs involving 8346 patients were included in this study. Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone, and the former had the highest probability of being the most effective option in this context. Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS. Owing to limited data, no definitive ranking could be determined for DFS. Considering nonsurgical SAEs, FLO has emerged as the safest treatment regimen. CONCLUSION: This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC. Further studies are required to validate these findings.

Knotted Artificial Muscles for Bio-mimetic Actuation under Deepwater.

Muscles featuring high frequency and high stroke linear actuation are essential for animals to achieve superior maneuverability, agility, and environmental adaptability. Artificial muscles are yet to match their biological counterparts, due to inferior actuation speed, magnitude, mode, or adaptability. Inspired by the hierarchical structure of natural muscles, we create artificial muscles that are powerful, responsive, robust, and adaptable. The artificial muscles consist of knots braided from 3D printed liquid crystal elastomer fibers and thin heating threads. The unique hierarchical, braided knot structure offers amplified linear stroke, force rate and damage-tolerance, verified by both numerical simulations and experiments. In particular, the square knotted artificial muscle shows reliable cycles of actuation at 1Hz in 3000m depth underwater. Potential application is demonstrated by propelling a model boat. Looking ahead, our knotted artificial muscles could empower novel biomedical devices and soft robots to explore various environments, from inside human body to the mysterious deep sea. This article is protected by copyright. All rights reserved.

Society for Immunotherapy of Cancer (SITC) recommendations on intratumoral immunotherapy clinical trials (IICT): from premalignant to metastatic disease.

BACKGROUND: Intratumorally delivered immunotherapies have the potential to favorably alter the local tumor microenvironment and may stimulate systemic host immunity, offering an alternative or adjunct to other local and systemic treatments. Despite their potential, these therapies have had limited success in late-phase trials for advanced cancer resulting in few formal approvals. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to determine how to design clinical trials with the greatest chance of demonstrating the benefits of intratumoral immunotherapy for patients with cancers across all stages of pathogenesis. METHODS: An Intratumoral Immunotherapy Clinical Trials Expert Panel composed of international key stakeholders from academia and industry was assembled. A multiple choice/free response survey was distributed to the panel, and the results of this survey were discussed during a half-day consensus meeting. Key discussion points are summarized in the following manuscript. RESULTS: The panel determined unique clinical trial designs tailored to different stages of cancer development-from premalignant to unresectable/metastatic-that can maximize the chance of capturing the effect of intratumoral immunotherapies. Design elements discussed included study type, patient stratification and exclusion criteria, indications of randomization, study arm determination, endpoints, biological sample collection, and response assessment with biomarkers and imaging. Populations to prioritize for the study of intratumoral immunotherapy, including stage, type of cancer and line of treatment, were also discussed along with common barriers to the development of these local treatments. CONCLUSIONS: The SITC Intratumoral Immunotherapy Clinical Trials Expert Panel has identified key considerations for the design and implementation of studies that have the greatest potential to capture the effect of intratumorally delivered immunotherapies. With more effective and standardized trial designs, the potential of intratumoral immunotherapy can be realized and lead to regulatory approvals that will extend the benefit of these local treatments to the patients who need them the most.

Frailty and psychiatric disorders: A bidirectional Mendelian randomization study.

BACKGROUND: The association between frailty and psychiatric disorders has been reported in observational studies. However, it is unclear whether frailty facilitates the appearance of psychiatric disorders or vice versa. Therefore, we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causality. METHODS: Independent genetic variants associated with frailty index (FI) and psychiatric disorders were obtained from large genome-wide association studies (GWAS). The inverse variance weighted method was utilized as the primary method to estimate causal effects, followed by various sensitivity analyses. Multivariable analyses were performed to further adjust for potential confounders. RESULTS: The present MR study revealed that genetically predicted FI was significantly and positively associated with the risk of major depressive disorder (MDD) (odds ratio [OR] 1.79, 95 % confidence interval [CI] 1.48-2.15, P = 1.06 × 10-9), anxiety disorder (OR 1.61, 95 % CI 1.19-2.18, P = 0.002) and neuroticism (OR 1.38, 95 % CI 1.18-1.61, P = 3.73 × 10-5). In the reverse MR test, genetic liability to MDD (beta 0.232, 95 % CI 0.189-0.274, P = 1.00 × 10-26) and neuroticism (beta 0.128, 95 % CI 0.081-0.175, P = 8.61 × 10-8) were significantly associated with higher FI. Multivariable analyses results supported the causal association between FI and MDD and neuroticism. LIMITATIONS: Restriction to European populations, and sample selection bias. CONCLUSIONS: Our study suggested a bidirectional causal association between frailty and MDD neuroticism, and a positive correlation of genetically predicted frailty on the risk of anxiety disorder. Developing a deeper understanding of these associations is essential to effectively manage frailty and optimize mental health in older adults.

Heat shock protein 71 restricts mutation of porcine reproductive and respiratory syndrome virus nsp2 in vitro.

porcine reproductive and respiratory syndrome (PRRS), caused by porcine reproductive and respiratory syndrome virus (PRRSV) infection, is an important swine infectious disease that causes substantial losses worldwide each year. PRRSV is a positive-sense single-stranded RNA virus that is highly susceptible to mutation and recombination, making vaccine and drug research for the disease extremely difficult. In this study, the binding of PRRSV nsp2 to HSP71 protein was detected by using the IP/MS technique. And the inhibitory effect of HSP71 on nsp2 antagonistic activity was validated by measuring NF-kB luciferase reporter. According to stress from inhibitory effects, the amino acid variation profile of PRRSV nsp2 under HSP71 stress was further analyzed using second-generation sequencing. Surprisingly, the results indicated that HSP71 pressure limits the random mutations of PRRSV nsp2 and maintains the dominant PRRSV strain within the population. Mutant strain showed weaker antagonistic activity and replication capability in cell. These results imply the binding of HSP71 with PRRSV nsp2 may lead to maintain the stability of highly virulent strains of PRRSV.

VSSI-GGD: A Variation Sparse EEG Source Imaging Approach Based on Generalized Gaussian Distribution.

Electroencephalographic (EEG) source imaging (ESI) is a powerful method for studying brain functions and surgical resection of epileptic foci. However, accurately estimating the location and extent of brain sources remains challenging due to noise and background interference in EEG signals. To reconstruct extended brain sources, we propose a new ESI method called Variation Sparse Source Imaging based on Generalized Gaussian Distribution (VSSI-GGD). VSSI-GGD uses the generalized Gaussian prior as a sparse constraint on the spatial variation domain and embeds it into the Bayesian framework for source estimation. Using a variational technique, we approximate the intractable true posterior with a Gaussian density. Through convex analysis, the Bayesian inference problem is transformed entirely into a series of regularized L2p -norm ( ) optimization problems, which are efficiently solved with the ADMM algorithm. Imaging results of numerical simulations and human experimental dataset analysis reveal the superior performance of VSSI-GGD, which provides higher spatial resolution with clear boundaries compared to benchmark algorithms. VSSI-GGD can potentially serve as an effective and robust spatiotemporal EEG source imaging method. The source code of VSSI-GGD is available at https://github.com/Mashirops/VSSI-GGD.git.

Paired electrocatalysis unlocks cross-dehydrogenative coupling of C(sp3)-H bonds using a pentacoordinated cobalt-salen catalyst.

Cross-dehydrogenative coupling of C(sp3)-H bonds is an ideal approach for C(sp3)-C(sp3) bond construction. However, conventional approaches mainly rely on a single activation mode by either stoichiometric oxidants or electrochemical oxidation, which would lead to inferior selectivity in the reaction between similar C(sp3)-H bonds. Herein we describe our development of a paired electrocatalysis strategy to access an unconventional selectivity in the cross-dehydrogenative coupling of alcoholic α C(sp3)-H with allylic (or benzylic) C-H bonds, which combines hydrogen evolution reaction catalysis with hydride transfer catalysis. To maximize the synergistic effect of the catalyst combinations, a HER catalyst pentacoordinated Co-salen is disclosed. The catalyst displays a large redox-potential gap (1.98 V) and suitable redox potential. With the optimized catalyst combination, an electrochemical cross-dehydrogenative coupling protocol features unconventional chemoselectivity (C-C vs. C-O coupling), excellent functional group tolerance (84 examples), valuable byproduct (hydrogen), and high regio- and site-selectivity. A plausible reaction mechanism is also proposed to rationalize the experimental observations.

An Efficient Probe-Based Quantitative PCR Assay Targeting Human-Specific DNA in ST6GALNAC3 for the Quantification of Human Cells in Preclinical Animal Models.

Precise quantification of human cells in preclinical animal models by a sensitive and specific approach is warranted. The probe-based quantitative PCR (qPCR) assay as a sensitive and swift approach is suitable for the quantification of human cells by targeting human-specific DNA sequences. In this study, we developed an efficient qPCR assay targeting human-specific DNA in ST6GALNAC3 (termed ST6GAL-qPCR) for the quantification of human cells in preclinical animal models. ST6GAL-qPCR probe was synthesized with FAM and non-fluorescent quencher-minor groove binder conjugated to the 5' and 3' end of the probe, respectively. Genomic DNA from human, rhesus monkeys, cynomolgus monkeys, New Zealand White rabbits, SD rats, C57BL/6, and BALB/c mice were utilized for analyzing the specificity and sensitivity of the ST6GAL-qPCR assay. The ST6GAL-qPCR assay targeted human-specific DNA was cloned to pUCM-T vector and released by EcoR I/Hind III digestion for generating a calibration curve. Cell mixing experiment was performed to validate the ST6GAL-qPCR assay by analysis of 0.1%, 0.01%, and 0.001% of human leukocytes mixed with murine thymocytes. The ST6GAL-qPCR assay detected human DNA rather than DNA from the tested animal species. The amplification efficiency of the ST6GAL-qPCR assay was 93% and the linearity of calibration curve was R2 = 0.999. The ST6GAL-qPCR assay detected as low as 5 copies of human-specific DNA and is efficient to specially amplify as low as 30-pg human DNA in the presence of 1 µg of DNA from the tested species, respectively. The ST6GAL-qPCR assay was able to quantify as low as 0.01% of human leukocytes within murine thymocytes. This ST6GAL-qPCR assay can be used as an efficient approach for the quantification of human cells in preclinical animal models.

CRISPR/Cas9-mediated enhancement of semi-dwarf glutinous traits in elite Xiangdaowan rice (Oryza sativa L.): targeting SD1 and Wx genes for yield and quality improvement.

In rice cultivation, the traits of semi-dwarfism and glutinous texture are pivotal for optimizing yield potential and grain quality, respectively. Xiangdaowan (XDW) rice, renowned for its exceptional aromatic properties, has faced challenges due to its tall stature and high amylose content, resulting in poor lodging resistance and suboptimal culinary attributes. To address these issues, we employed CRISPR/Cas9 technology to precisely edit the SD1 and Wx genes in XDW rice, leading to the development of stable genetically homozygous lines with desired semi-dwarf and glutinous characteristics. The sd1-wx mutant lines exhibited reduced gibberellin content, plant height, and amylose content, while maintaining hardly changed germination rate and other key agronomic traits. Importantly, our study demonstrated that exogenous GA3 application effectively promoted growth by compensating for the deficiency of endogenous gibberellin. Based on this, a semi-dwarf glutinous elite rice (Oryza sativa L.) Lines was developed without too much effect on most agronomic traits. Furthermore, a comparative transcriptome analysis unveiled that differentially expressed genes (DEGs) were primarily associated with the anchored component of the membrane, hydrogen peroxide catabolic process, peroxidase activity, terpene synthase activity, and apoplast. Additionally, terpene synthase genes involved in catalyzing the biosynthesis of diterpenoids to gibberellins were enriched and significantly down-regulated. This comprehensive study provides an efficient method for simultaneously enhancing rice plant height and quality, paving the way for the development of lodging-resistant and high-quality rice varieties.

Intermittent fasting and health outcomes: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials.

Background: Benefits of Intermittent fasting (IF) on health-related outcomes have been found in a range of randomised controlled trials (RCTs). Our umbrella review aimed to systematically analyze and synthesize the available causal evidence on IF and its impact on specific health-related outcomes while evaluating its evidence quality. Methods: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane databases (from inception up to 8 January 2024) to identify related systematic reviews and meta-analyses of RCTs investigating the association between IF and human health outcomes. We recalculated the effect sizes for each meta-analysis as mean difference (MD) or standardized mean difference (SMD) with corresponding 95% confidence intervals (CIs). Subgroup analyses were performed for populations based on three specific status: diabetes, overweight or obesity, and metabolic syndrome. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. This study is registered with PROSPERO (CRD42023382004). Findings: A total of 351 associations from 23 meta-analyses with 34 health outcomes were included in the study. A wide range of outcomes were investigated, including anthropometric measures (n = 155), lipid profiles (n = 83), glycemic profiles (n = 57), circulatory system index (n = 41), appetite (n = 9), and others (n = 6). Twenty-one (91%) meta-analyses with 346 associations were rated as high confidence according to the AMSTAR criteria. The summary effects estimates were significant at p < 0.05 in 103 associations, of which 10 (10%) were supported by high certainty of evidence according to GRADE. Specifically, compared with non-intervention diet in adults with overweight or obesity, IF reduced waist circumference (WC) (MD = -1.02 cm; 95% CI: -1.99 to -0.06; p = 0.038), fat mass (MD = -0.72 kg; 95% CI: -1.32 to -0.12; p = 0.019), fasting insulin (SMD = -0.21; 95% CI: -0.40 to -0.02; p = 0.030), low-density lipoprotein cholesterol (LDL-C) (SMD = -0.20; 95% CI: -0.38 to -0.02; p = 0.027), total cholesterol (TC) (SMD = -0.29; 95% CI: -0.48 to -0.10; p = 0.003), and triacylglycerols (TG) (SMD = -0.23; 95% CI: -0.39 to -0.06; p = 0.007), but increased fat free mass (FFM) (MD = 0.98 kg; 95% CI: 0.18-1.78; p = 0.016). Of note, compared with the non-intervention diet, modified alternate-day fasting (MADF) reduced fat mass (MD = -0.70 kg; 95% CI: -1.38 to -0.02; p = 0.044). In people with overweight or obesity, and type 2 diabetes, IF increases high-density lipoprotein cholesterol (HDL-C) levels compared to continuous energy restriction (CER) (MD = 0.03 mmol/L; 95% CI: 0.01-0.05; p = 0.010). However, IF was less effective at reducing systolic blood pressure (SBP) than a CER diet in adults with overweight or obesity (SMD = 0.21; 95% CI: 0.05-0.36; p = 0.008). Interpretation: Our findings suggest that IF may have beneficial effects on a range of health outcomes for adults with overweight or obesity, compared to CER or non-intervention diet. Specifically, IF may decreased WC, fat mass, LDL-C, TG, TC, fasting insulin, and SBP, while increasing HDL-C and FFM. Notably, it is worth noting that the SBP lowering effect of IF appears to be weaker than that of CER. Funding: This work was supported by the National Key Research and Development Program of China (Q-JW), the Natural Science Foundation of China (Q-JW and T-TG), Outstanding Scientific Fund of Shengjing Hospital of China Medical University (Q-JW), and 345 Talent Project of Shengjing Hospital of China Medical University (T-TG).

Exploration of the molecular biological mechanisms and review of postoperative radiotherapy cases in tenosynovial giant cell tumors.

Tendon Sheath Giant Cell Tumor (TGCT) is a benign tumor that primarily grows within joints and bursae. However, it has a high postoperative recurrence rate, ranging from 15% to 45%. Although radiotherapy may reduce this recurrence rate, its applicability as a standard treatment is still controversial. Furthermore, the pathogenic mechanisms of TGCT are not clear, which limits the development of effective treatment methods. The unpredictable growth and high recurrence rate of TGCT adds to the challenges of disease management. Currently, our understanding of TGCT mainly depends on pathological slice analysis due to a lack of stable cell models. In this study, we first reviewed the medical records of two female TGCT patients who had undergone radiotherapy. Then, by combining bioinformatics and machine learning, we interpreted the pathogenesis of TGCT and its associations with other diseases from multiple perspectives. Based on a deep analysis of the case data, we provided empirical support for postoperative radiotherapy in TGCT patients. Additionally, our further analysis revealed the signaling pathways of differentially expressed genes in TGCT, as well as its potential associations with osteoarthritis and synovial sarcomas.