The influence of Mg/Al molar ratio on the performance of CuMgAl-x catalysts for CO2 hydrogenation to methanol.

The CuMgAl-x catalysts derived from hydrotalcite precursors with different Mg/Al molar ratios were synthesized and applied to CO2 hydrogenation to methanol reaction. In this study, the effects of Mg/Al molar ratio on the structure and surface properties of CuMgAl-x catalysts were investigated by XRD, N2 adsorption-desorption, SEM, TEM, H2-TPR, CO2-TPD, XPS, and in situ DRIFTS characterization methods. The results showed that an appropriate Mg/Al molar ratio can enhance the Cu-MgO interaction, increasing the basic sites and obtaining suitable acid sites. The dispersion of active Cu on the CuMgAl-x catalysts can be improved by strong Cu-MgO interaction, which enhances the adsorption capacity of CO2 and makes H2 activation easier, accelerates the conversion of intermediate species CO3 * and HCO3 *to HCOO*, and facilitates further conversion to CH3O* and CH3OH. The strong interaction between Cu and MgO was conducive to the formation of Cu+, which can inhibit the desorption of CO in the reverse water gas shift reaction. The CuMgAl-3 catalyst showed the highest CO2 Conversion rate (14.3%), methanol selectivity (94.5%), and STY of methanol (419.3 g⋅kgcat. -1⋅h-1) at 240°C and 2.5 MPa. The results obtained in this paper can provide a new idea for the design of high-performance catalysts for CO2 hydrogenation to methanol.

Advances in application of CRISPR-Cas13a system.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and CRISPR-associated (Cas) proteins serve as an adaptive immune system that safeguards prokaryotes and some of the viruses that infect prokaryotes from foreign nucleic acids (such as viruses and plasmids). The genomes of the majority of archaea and about half of all bacteria contain various CRISPR-Cas systems. CRISPR-Cas systems depend on CRISPR RNAs (crRNAs). They act as a navigation system to specifically cut and destroy foreign nucleic acids by recognizing invading foreign nucleic acids and binding Cas proteins. In this review, we provide a brief overview of the evolution and classification of the CRISPR-Cas system, focusing on the functions and applications of the CRISPR-Cas13a system. We describe the CRISPR-Cas13a system and discuss its RNA-directed ribonuclease function. Meanwhile, we briefly introduce the mechanism of action of the CRISPR-Cas13a system and summarize the applications of the CRISPR-Cas13a system in pathogen detection, eukaryotes, agriculture, biosensors, and human gene therapy. We are right understanding of CRISPR-Cas13a has been broadened, and the CRISPR-Cas13a system will be useful for developing new RNA targeting tools. Therefore, understanding the basic details of the structure, function, and biological characterization of CRISPR-Cas13a effector proteins is critical for optimizing RNA targeting tools.

The deletion of ppr2 interferes iron sensing and leads to oxidative stress response in Schizosaccharomyces pombe.

Pentatricopeptide repeat proteins are involved in mitochondrial both transcriptional and posttranscriptional regulation. Schizosaccharomyces pombe Ppr2 is a general mitochondrial translation factor that plays a critical role in the synthesis of all mitochondrial DNA-encoded oxidative phosphorylation subunits, which are essential for mitochondrial respiration. Our previous analysis showed that ppr2 deletion resulted in increased expression of iron uptake genes and caused ferroptosis-like cell death in S. pombe. In the present work, we showed that deletion of ppr2 reduced viability on glycerol- and galactose-containing media.Php4 is a transcription repressor that regulates iron homeostasis in fission yeast. We found that in the ppr2 deletion strain, Php4 was constitutively active and accumulated in the nucleus in the stationary phase. We also found that deletion of ppr2 decreased the ferroptosis-related protein Gpx1 in the mitochondria. Overexpression of Gpx1 improves the viability of Δppr2 cells. We showed that the deletion of ppr2 increased the production of ROS, downregulated heme synthesis and iron-sulfur cluster proteins, and induced stress proteins. Finally, we observed the nuclear accumulation of Pap1-GFP and Sty1-GFP, suggesting that Sty1 and Pap1 in response to cellular stress in the ppr2 deletion strain. These results suggest thatppr2 deletion may cause mitochondrial dysfunction, which is likely to lead to iron-sensing defect and iron starvation response, resulting in perturbation of iron homeostasis and increased hydroxyl radical production. The increased hydroxyl radical production triggers cellular responses in theppr2 deletion strain.

Validity of the modified versions of SARC-F+EBM for sarcopenia screening and diagnosis in China: the PPLSS study.

BACKGROUND AND OBJECTIVES: It is recommended by Asian Working Group for Sarcopenia to early identify people at risk for sarcopenia using simple screening tools like SARC-F. The modified version SARC-F+EBM showed higher diagnostic performance. However, this cut-off value of body mass index (BMI) remained uncertain to be used in Chinese population. In this study, we used appropriate BMI recommended for Chinese older population and further modified SARC-F+EBM by combining calf circumference. METHODS AND STUDY DESIGN: Diagnostic tests were performed and the receiver operating characteristics analyses were conducted between the SARC-F, SARC-F+EBM (cut-off of BMI: ≤ 21 kg/m2), SARC-F+EBM (CN) (cut-off of BMI: ≤ 22 kg/m2), SARC-CalF and SARC-CalF+EBM (CN) (cut-off of BMI: ≤ 22 kg/m2) in 1660 community-dwelling participants aged ≥ 65 years from China. RESULTS: The participants had an average age of 71.7±5.1 years, of which 56.8% were women. All the modified models could enhance the areas under the receiver operating characteristic curve (AUC) of original SARC-F (all p<0.001). The SARC-F+EBM (CN) also showed a significantly higher sensitivity of 47.4% (p<0.001) and an AUC of 0.809 (p=0.005) than SARC-F+EBM. SARC-CalF+EBM (CN) was validated to be of great diagnostic value of the highest AUC of 0.88 among these sarcopenia screening tools, including SARC-F, SARC-CalF and SARC-F+EBM (CN) (all p<0.001). Using this study population as a reference, the optimal cut-off value of SARC-CalF+EBM (CN) is ≥12 points, with a sensitivity of 79.3% and a specificity of 80.7%. CONCLUSIONS: The SARC-F+EBM (CN) and SARC-CalF+EBM (CN) could enhance the diagnostic performance of SARC-F and SARC-F+EBM and are suitable sarcopenia screening tools for Chinese population.

Transcriptome in Liver of Periparturient Dairy Cows Differs between Supplementation of Rumen-Protected Niacin and Rumen-Protected Nicotinamide.

To investigate the difference between rumen-protected niacin (RPN) and rumen-protected nicotinamide (RPM) in the transcriptome of genes relating to the lipid metabolism of the liver of periparturient dairy cows, 10 healthy Chinese Holstein cows were randomly divided into two groups and fed diets supplemented with 18.4 g/d RPN or 18.7 g/d RPM, respectively. The experiment lasted from 14 days before to 21 days after parturition. Liver biopsies were taken 21 days postpartum for transcriptomic sequencing. In addition, human LO2 cells were cultured in a medium containing 1.6 mmol/L of non-esterified fatty acids and 1 mmol/L niacin (NA) or 2 mmol/L nicotinamide (NAM) to verify the expression of the 10 genes selected from the transcriptomic analysis of the liver biopsies. The expression of a total of 9837 genes was detected in the liver biopsies, among which 1210 differentially expressed genes (DEGs) were identified, with 579 upregulated and 631 downregulated genes. These DEGs were associated mainly with lipid metabolism, oxidative stress, and some inflammatory pathways. Gene ontology (GO) enrichment analysis showed that 355 DEGs were enriched in 38 GO terms. The differences in the expression of these DEGs between RPN and RPM were predominantly related to the processes of steroid catabolism, steroid hydroxylase, monooxygenase activity, oxidoreductase activity, hemoglobin binding, and ferric iron binding, which are involved mainly in lipid anabolism and redox processes. The expressions of FADS2, SLC27A6, ARHGAP24, and THRSP in LO2 cells were significantly higher (p < 0.05) while the expressions of BCO2, MARS1, GARS1, S100A12, AGMO, and OSBPL11 were significantly lower (p < 0.05) on the NA treatment compared to the NAM treatment, indicating that NA played a role in liver metabolism by directly regulating fatty acid anabolism and transport, inflammatory factor expression, and oxidative stress; and NAM functioned more as a precursor of nicotinamide adenine dinucleotide (NAD, coenzyme I) and nicotinamide adenine dinucleotide phosphate (NADP, coenzyme II) to participate indirectly in biological processes such as ether lipid metabolism, cholesterol metabolism, energy metabolism, and other processes.

High-frequency dynamics of CO2 emission flux and its influencing factors in a subtropical karst groundwater-fed reservoir, south China.

Revealing the magnitude, dynamics, and influencing factors of CO2 emissions across the water-air interface in karst water with high frequency is crucial for accurately assessing the carbon budget in a karst environment. Due to the limitations of observation methods, the current research is still very insufficient. To solve the above problems and clarify the main influencing factors of CO2 emission in karst water, this study selected Dalongdong (DLD) Reservoir, located in the typical karst peak and valley area in southwest China, to carry out a multi-parameter high-frequency monitoring study from January to December 2021, and used the thin boundary model method to estimate the CO2 flux across the water-air interface (CF). The average annual flux of DLD reservoir is 84.48 mmol·(m2·h)-1, which represents a CO2 source overall. However, during the stratification period in August, there is a transient carbon sink due to negative CO2 emission. The alteration of thermal stratification in water is crucial in regulating the seasonal variation of CF. Meanwhile, the diurnal variation is significantly influenced by changes in hydrochemical parameters during the thermal stratification stage. Compared to low wind speeds (<3 m/s), high wind speeds (≥3 m/s) have a greater impact on the CO2 flux. Furthermore, high-frequency continuous data revealed that the reservoir triggered a CO2 pulse emission during the turnover process, primarily at night, leading to unusually high CO2 flux values. It is of great significance to monitor and reveal the process, flux, and control factors of CO2 flux in land water at a high-frequency strategy. They will help improve the accuracy of regional or watershed carbon budgets and clarify the role of global land water in the global carbon budget.

Preparation of genetically or chemically engineered exosomes and their therapeutic effects in bone regeneration and anti-inflammation.

The treatment of bone or cartilage damage and inflammation-related diseases has been a long-standing research hotspot. Traditional treatments such as surgery and cell therapy have only displayed limited efficacy because they can't avoid potential deterioration and ensure cell activity. Recently, exosomes have become a favorable tool for various tissue reconstruction due to their abundant content of proteins, lipids, DNA, RNA and other substances, which can promote bone regeneration through osteogenesis, angiogenesis and inflammation modulation. Besides, exosomes are also promising delivery systems because of stability in the bloodstream, immune stealth capacity, intrinsic cell-targeting property and outstanding intracellular communication. Despite having great potential in therapeutic delivery, exosomes still show some limitations in clinical studies, such as inefficient targeting ability, low yield and unsatisfactory therapeutic effects. In order to overcome the shortcomings, increasing studies have prepared genetically or chemically engineered exosomes to improve their properties. This review focuses on different methods of preparing genetically or chemically engineered exosomes and the therapeutic effects of engineering exosomes in bone regeneration and anti-inflammation, thereby providing some references for future applications of engineering exosomes.

Gut microbiota changes associated with low-carbohydrate diet intervention for obesity.

Low-carbohydrate diets (LCDs) are frequently recommended for alleviating obesity, and the gut microbiota plays key roles in energy metabolism and weight loss. However, there is limited in-human research on how LCD changes gut microbiota. In this before-after study, 43 participants were assigned to the LCD intervention for 4 weeks. The main objective was to investigate the specific changes that occur in the participants' microbiome in response to the LCD. Changes in gut microbiota were analyzed using 16s rRNA sequencing. Body composition was measured using InBody 770. Remarkably, 35 participants (79.07%) lost more than 5% of their body weight; levels of BMI, body fat, and total cholesterol were significantly decreased, indicating the effectiveness of the LCD intervention. The richness of microbiota significantly increased after the intervention. By taking the intersection of ANOVA and linear discriminant analysis effect size (LEfSe) analysis results, we identified three phyla, three classes, four orders, five families, and six genera that were differentially enriched between baseline and week-4 time points. Among the three phyla, relative abundances of Firmicutes and Actinobacteriota decreased significantly, while Bacteroidetes increased significantly. At the genus level, Ruminococcus, Agathobacter, Streptococcus, and Bifidobacterium showed a significant reduction in relative abundances, whereas Parabacteroides and Bacteroides increased steadily. Our results demonstrate that LCD can effectively alleviate obesity and modify certain taxa of gut microbiota, providing potential insights for personalized dietary interventions against obesity.

Uncovering the world's largest carbon sink-a profile of ocean carbon sinks research.

As the world's largest carbon sink, the oceans are essential to achieving the 1.5 °C target. Marine ecosystems play a crucial role in the "sink enhancement" process. A deeper comprehension of research trends, hotspots, and the boundaries of ocean carbon sinks is necessary for a more effective response to climate change. To this end, academic literature in the field of ocean carbon sinks was investigated and analyzed using the core database of the Web of Science. The results show that (1) The ocean carbon sink is a global study. The number of literatures in the field of ocean carbon sinks is growing, and the USA and China are the main leaders, with the USA accounting for 31.19% of the global publications and China accounting for 26.57% of the global publications, and the environmental science discipline is the most popular in this field. (2) Keyword burst detection shows that the keywords "sink, sensitivity, land, dynamics, and seagrass" appear earliest and have high burst intensity, which are the hot spots of research in this field; the keyword clustering shows that the global ocean carbon sinks research mainly focuses on three themes: (i) carbon cycle and climate change; (ii) carbon sinks estimation models and techniques; and (iii) carbon sinks capacity and ocean biological carbon sequestration in different seas. Finally, targeted research recommendations are proposed to further match the ocean carbon sink research.

Abnormalities of retinal function in type 2 diabetes mellitus patients without clinical diabetic retinopathy detected by multifocal electroretinogram.

OBJECTIVE: To study the changes of retinal function in type 2 diabetes mellitus(DM) patients without apparently diabetic retinopathy via multifocal electroretinogram. METHODS: Thirty-six type 2 DM patients (72 eyes) without visible diabetic retinopathy were selected as the experimental group, and thirty-five healthy subjects (70 eyes) were selected as the control group. All subjects were underwent multifocal electroretinogram (mf- ERG). RESULTS: Compared with the control group, the implicit time delay of the P1 wave in the first ring, third ring, fourth ring, and fifth ring of the experimental group was significant (t = -3.154, p = 0.004, t = -8.21, p = 0.000, t = -3.067, p = 0.004, t = -4.443, p = 0.000, respectively). The implicit time of the N1 wave in the fourth- and fifth-ring were also significantly delayed compared with the control group (t = -3.549, p = 0.001, t = 2.961, p = 0.005, respectively). Compared with the control group, the implicit time of the P1 wave and N1 wave in the temporal region of the experimental group were delayed (t = -2.148, p = 0.037, t = -2.834, p = 0.007, respectively). There were no significant difference between the experimental group and the control group of the temporal area in the amplitude density of P1 wave, N1 wave. There was no difference in the implicit time and amplitude density of the N1 and P1 waves in the nasal region between the experimental group and the control group. The multifocal electroretinogram complex parameters showed better specificity and sensitivity in the diagnosis of diabetic retinopathy. CONCLUSION: The multifocal electroretinogram can detect abnormal changes in the retina of type 2 DM patients without visible diabetic retinopathy. The multifocal electroretinogram complex parameter is a potential indicator for the early diagnosis of diabetic retinopathy.

Impact of different geopolitical factors on the energy transition: The role of geopolitical threats, geopolitical acts, and geopolitical risks.

In order to better understand the impact of different geopolitical factors on energy transition, the impact of geopolitical threats (war threats, peace threats, military buildups, nuclear threats and terror threats), geopolitical acts (beginning of war, escalation of war and terror acts), and geopolitical risks on energy transition were systematically investigated. Green technologies, natural resource rents and trade openness were incorporated into the analytical framework, and a dynamic panel threshold model was utilized to explore the impact of geopolitical risks on energy transition across different income levels. To this end, data on geopolitical threats, geopolitical acts, geopolitical risks, energy transitions and other key social economic factors for 38 countries from 2000 to 2022 were collected. The heterogeneity simulation results show that there is a negative correlation between geopolitical threats, geopolitical acts, geopolitical risks and energy transition. Moreover, geopolitical threats have more significant hindrance to the energy transition than geopolitical acts. The results of the nonlinear panel simulation show that there is a double threshold effect of geopolitical risks on energy transition. When geopolitical risk crosses the threshold (0.5197), the coefficient decreases to -0.29, which means that the rising geopolitical risk increases the inhibition on energy transition, and the inhibitory effect is slightly weakened after a certain level. Finally, policy implications are offered.

E3 ubiquitin ligase Hul6 modulates iron-dependent metabolism by regulating Php4 stability.

Schizosaccharomyces pombe Php4 is the regulatory subunit of the CCAAT-binding complexes and plays an important role in the regulation of iron homeostasis and iron-dependent metabolism. Here, we show that Php4 undergoes ubiquitin-dependent degradation in the late logarithmic and stationary phases. The degradation and ubiquitination of Php4 could be attenuated by deletion of hul6, a gene encoding a putative HECT-type E3 ubiquitin ligase. The expression levels of Hul6 and Php4 are oppositely regulated during cell growth. Hul6 interacts with the C-terminal region of Php4. Two lysine residues (K217 and K274) located in the C-terminal region of Php4 are required for its polyubiquitination. Increasing the levels of Php4 by deletion of hul6 or overexpression of php4 decreased expression of Php4 target proteins involved in iron-dependent metabolic pathways such as the tricarboxylic cycle and mitochondrial oxidative phosphorylation, thus causing increased sensitivity to high-iron and reductions in succinate dehydrogenase and mitochondrial complex II activities. Hul6 is located primarily in the mitochondrial outer membrane and most likely targets cytosolic Php4 for ubiquitination and degradation. Taken together, our data suggest that Hul6 regulates iron-dependent metabolism through degradation of Php4 under normal growth conditions. Our results also suggest that Hul6 promotes iron-dependent metabolism to help the cell to adapt to a nutrient-starved growth phase.

Cardiometabolic diseases and early cognitive decline: Mitigated by integrated active lifestyle for brain health.

BACKGROUND: Cardiometabolic diseases (CMDs) increases the risk of cognitive decline, but the extent to which this can be offset by adherence to an active integrated lifestyle is unknown. METHODS: This prospective study used the baseline and 2-year follow-up data of 2537 dementia-free elderly ≥60 from PINDEC Project. Lifestyle factors (including physical exercise, social interaction, leisure activities, sleep quality, smoking, and alcohol consumption) were collected and the integrated score was calculated. Participants were divided into three groups based on integrated score tertiles (inactive, ≤3 score; intermediate, 4 score; and active, ≥5). Logistic regression was used in data analysis. RESULTS: 35.2 % participants had 5-6 healthy components, while only 5.4 % had all 6 healthy lifestyles. The multiadjusted odds ratios (ORs, 95 % confidence interval) of early cognitive decline was 1.223 (0.799-1.871) and 1.832 (1.140-2.943) for participants with only one CMD and any two or more CMDs, respectively. An inverse dose-response relationship was found between lifestyle scores and early cognitive decline (Ptrend = 0.017). In participants with active lifestyle, the OR for early cognitive decline comparing the CMDs status of any two or more CMDs vs. CMDs-free was 0.778 (95%CI: 0.302-2.007). Participants with inactive lifestyle and any two or more CMDs had a near 3.4-fold increased risk of early cognitive decline than those without CMDs who had intermediate to active lifestyle (OR = 3.422, 95%CI: 1.764-6.638). LIMITATIONS: Our research lacks information about nutrition. CONCLUSIONS: A dose-response relationship exists between CMDs status and risk of early cognitive decline. However, adherence to an active integrated lifestyle may mitigate this risk.

Cohort profile: Beijing Healthy Aging Cohort Study (BHACS).

The Beijing Healthy Aging Cohort Study (BHACS) was established to supplement the limited data of a large representative cohort of older people based on the general population and was designed to evaluate the prevalence, incidence, and natural history of cognitive decline, functional disability, and conventional vascular risk factors. The aim was to determine the evolution of these conditions by estimating the rates and determinants of progression and regression to adverse outcomes, including dementia, cardiovascular events, cancer, and all-cause death. It can therefore provide evidence to help policy makers develop better policies to promote healthy aging in China. BHACS consisted of three cohorts (BLSA, CCHS-Beijing, and BECHCS) in Beijing with a total population of 11 235 (6281 in urban and 4954 in rural areas) and an age range of 55 years or older (55-101 years) with a mean age of 70.35 ± 7.71 years (70.69 ± 7.62 years in urban and 69.92 ± 7.80 years in rural areas). BHACS-BLSA conducted the baseline survey in 2009 with a multistage stratification-random clustering procedure for people aged 55 years or older; BHACS-CCHS-Beijing conducted the baseline survey in 2013-2015 with a stratified multistage cluster random sampling method for people aged 55 years or older; and BHACS-BECHCS conducted the baseline survey in 2010-2014 with two-stage cluster random sampling method for people aged 60 years or older. Data were collected through questionnaires, physical measurements, and laboratory analyses. Topics covered by BHACS include a wide range of physical and mental health indicators, lifestyles and personal, family, and socio-economic determinants of health. There are no immediate plans to make the cohort data freely available to the public, but specific proposals for further collaboration are welcome. For further information and collaboration, please contact the corresponding author Yao He (e-mail: yhe301@x263.net).

Evodiamine inhibits EPRS expression to regulate glutamate metabolism and proliferation of oral squamous cell carcinoma cells.

The effects of evodiamine (EVO) on oral squamous cell carcinoma (OSCC) are not yet understood. Based on our earlier findings, we hypothesized that evodiamine may affect OSCC cell proliferation and glutamate metabolism by modulating the expression of EPRS (glutamyl-prolyl-tRNA synthetase 1). From GEPIA, we obtained EPRS expression data in patients with OSCC as well as survival prognosis data. An animal model using Cal27 cells in BALB/c nude mice was established. The expression of EPRS was assessed by immunofluorescence, Western blotting, and quantitative PCR. Glutamate measurements were performed to evaluate the impact of evodiamine on glutamate metabolism of Cal27 and SAS tumor cells. transient transfection techniques were used to knock down and modulate EPRS in these cells. EPRS is expressed at higher levels in OSCC than in normal tissues, and it predicts poor prognosis in patients. In a nude mouse xenograft model, evodiamine inhibited tumor growth and the expression of EPRS. Evodiamine impacted cell proliferation, glutamine metabolism, and EPRS expression on Cal27 and SAS cell lines. In EPRS knockdown cell lines, both cell proliferation and glutamine metabolism are suppressed. EPRS's overexpression partially restores evodiamine's inhibitory effects on cell proliferation and glutamine metabolism. This study provides crucial experimental evidence supporting the potential therapeutic application of evodiamine in treating OSCC. Evodiamine exhibits promising anti-tumor effects by targeting EPRS to regulate glutamate metabolism.

Heterozygous variants of NOD2, IL10RA, PLA2G6 and COL7A1 correlate with Crohn's disease.

To identify candidate pathogenic genes of early-stage Crohn's disease (CD) and predict potential roles of genetic factors in CD, we performed whole exome sequencing on a child with early-stage Crohn's disease (CD) and her parents (core family), found that the patient carried heterozygous variants of 4 genes: NOD2 c. 2257 C > T, IL10RA c. 301 C > T, PLA2G6 c. 2029 C > T, COL7A1 c. 3190 G > A. Heterozygous variants of NOD2, IL10RA, PLA2G6 and COL7A1, intestinal inflammatory response is triggered, normal intestinal wall tissue damage, leading to CD phenotype.

Different Acupuncture Therapies for Postherpetic Neuralgia: An Overview of Systematic Reviews and Meta-analysis.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster infection and affects patients' quality of life. Acupuncture therapy is regarded as a competitive method of treatment for analgesia. OBJECTIVE: To summarize evidence from systematic reviews (SRs) and evaluate the effectiveness and safety of different acupuncture therapies for treating PHN. METHODS: Eight electronic databases were searched from their inception to August 5, 2022, including 4 international electronic databases (PubMed, EMBASE, the Cochrane Library, and Web of Science) and 4 Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database). Methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The Risk of Bias in Systematic Review (ROBIS) tool was used to assess the risk of bias in SRs. Evidence level was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Totally, 7 SRs were included, including 128 studies and 9,792 patients. In AMSTAR 2, most of the SRs were of low or critically low levels since they had more than 1 critical deficiency. In ROBIS, 1 SR (14.29%) was rated as high risk, and the other 6 (85.71%) were rated as low risk. In the GRADE system, 9 outcomes (28.13%) were valued as high level, 5 (15.63%) as moderate level, 1 (3.13%) as low, and 17 (53.13%) as very low. In the effectiveness of acupuncture therapy, the group "moxibustion vs. original medical treatment" [mean difference (MD)=-1.44, 95% confidence interval (CI): -1.80 to -1.08, I2=99%, P<0.00001] was of the highest heterogeneity and the group "bloodletting vs. original medical treatment" (MD=-2.80, 95% CI: -3.14 to -2.46, I2=0, P<0.00001) was of the lowest heterogeneity. Six SRs have reported the safety of their studies and no serious events were shown in the treatment and control groups. CONCLUSIONS: Acupuncture therapy seems to be effective in treating PHN. Despite the evidence that suggested the advantages of acupuncture therapy in relieving pain and promoting efficacy and safety, the methodological quality was quite low. Further studies should pay more attention to the quality of original studies and evidence for SRs to confirm these findings. (PROSPERO registration No. CRD42022344790).

Design, synthesis and antitumor activity of 4-arylamine substituted pyrimidine derivatives as noncovalent EGFR inhibitors overcoming C797S mutation.

Clinical researches have shown that epidermal growth factor receptor (EGFR) is a key target for treatment of non-small cell lung cancer (NSCLC). Many EGFR inhibitors were successfully developed as ani-tumor drugs to treat NSCLC patients. Unfortunately, drug resistances were found in clinic. To overcome C797S mutation in EGFR, a novel series of 4-arylamine substituted pyrimidine derivatives were designed and synthesized under the principle of structure-based drug design. Interestingly, compounds 6e and 9i demonstrated the best anti-proliferative activity against A549, NCI-H1975, and HCC827 cells. In particular, the IC50 values against HCC827 cells reached to 24.6 nM and 31.6 nM, which were much lower than human normal cells 2BS and LO2. Furthermore, compounds 6e and 9i showed extraordinary activity against EGFR19del/T790M/C797S (IC50 = 16.06 nM and 37.95 nM) and EGFRL858R/T790M/C797S (IC50 = 11.81 nM and 26.68 nM), which were potent than Osimertinib (IC50 = 52.28 nM and 157.60 nM). Further studies have shown that compounds 6e and 9i could pertain inhibition of HCC827 colony formation, and arrest HCC827 cells at G2/M phase. Moreover, the most promising compound 6e could inhibit the migration of HCC827 cells, induce HCC827 cells apoptosis, and significantly inhibit the phosphorylation of EGFR, AKT and Erk1/2. In vivo xenograft mouse model with HCC827 cells, compound 6e resulted in remarkable tumor regression without obvious toxicity. In addition, molecular docking studies suggested that compound 6e could firmly combine with T790M-mutant, T790 M/C797S-mutant, and L858R/T790 M/C797S-mutant EGFR kinases as ATP-competitive inhibitor.

Fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasis.

INTRODUCTION: Metastasis is an important cause of high mortality and lethality of oral cancer. Fusobacterium nucleatum (Fn) can promote tumour metastasis. Outer membrane vesicles (OMVs) are secreted by Fn. However, the effects of Fn-derived extracellular vesicles on oral cancer metastasis and the underlying mechanisms are unclear. OBJECTIVES: We aimed to determine whether and how Fn OMVs mediate oral cancer metastasis. METHODS: OMVs were isolated from brain heart infusion (BHI) broth supernatant of Fn by ultracentrifugation. Tumour-bearing mice were treated with Fn OMVs to evaluate the effect of OMVs on cancer metastasis. Transwell assays were performed to determine how Fn OMVs affect cancer cell migration and invasion. The differentially expressed genes in Fn OMV-treated/untreated cancer cells were identified by RNA-seq. Transmission electron microscopy, laser confocal microscopy, and lentiviral transduction were used to detect changes in autophagic flux in cancer cells stimulated with Fn OMVs. Western blotting assay was performed to determine changes in EMT-related marker protein levels in cancer cells. Fn OMVs' effects on migration after blocking autophagic flux by autophagy inhibitors were determined by in vitro and in vivo experiments. RESULTS: Fn OMVs were structurally similar to vesicles. In the in vivo experiment, Fn OMVs promoted lung metastasis in tumour-bearing mice, while chloroquine (CHQ, an autophagy inhibitor) treatment reduced the number of pulmonary metastases resulting from the intratumoral Fn OMV injection. Fn OMVs promoted the migration and invasion of cancer cells in vivo, leading to altered expression levels of EMT-related proteins (E-cadherin downregulation; Vimentin/N-cadherin upregulation). RNA-seq showed that Fn OMVs activate intracellular autophagy pathways. Blocking autophagic flux with CHQ reduced in vitro and in vivo migration of cancer cells induced by Fn OMVs as well as reversed changes in EMT-related protein expression. CONCLUSION: Fn OMVs not only induced cancer metastasis but also activated autophagic flux. Blocking autophagic flux weakened Fn OMV-stimulated cancer metastasis.

Does medical waste research during COVID-19 meet the challenge induced by the pandemic to waste management?

The COVID-19 pandemic has resulted in an unprecedented amount of medical waste, presenting significant challenges for the safe disposal of hazardous waste. A systematic review of existing research on COVID-19 and medical waste can help address these challenges by providing insights and recommendations for effective management of the massive medical waste generated during the pandemic. This study utilized bibliometric and text mining methods to survey the scientific outcomes related to COVID-19 and medical waste, drawing on data from the Scopus database. The results show that the spatial distribution of medical waste research is unbalanced. Surprisingly, developing countries rather than developed countries lead research in this area. Especially, China, a major contributor to the field, has the highest number of publications and citations, and is also a centre of international cooperation. The main study authors and research institutions are also mainly from China. And the research on medical waste is a multidisciplinary field. Text mining analysis shows that COVID-19 and medical waste research is mainly organized around four themes: (i) medical waste from personal protective equipment; (ii) research on medical waste in Wuhan, China; (iii) threats of medical waste to the environment and (iv) disposal and management of medical waste. This would serve to better understand the current state of medical waste research and to provide some implications for future research.