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Background: This study aims to explore the relationship between magnesium depletion score (MDS) and periodontitis in US adults using data from the National Health and Nutritional Examination Survey (NHANES) 2009-2014., Methods: This cross-sectional study's outcome was periodontitis, defined by the CDC/AAP using clinical periodontal parameters. The exposure of this study was MDS, which was calculated according to four parameters (diuretic use, proton pump inhibitor use, renal function and alcohol consumption). Weighted univariable and multivariable logistic regression analyses were performed to explore the association between MDS intake and periodontitis. Confounding factors included in the adjusted model were age, sex, race, income, smoking status, dietary magnesium, obesity, diabetes, hypertension, education level, recreational activity, and work activity., Results: A total of 8,628 participants over the age 30 were included in our study. Individuals with high level of magnesium deficiency were more likely referred to poorer periodontal health in both crude model (OR = 2.01, 95% CI: 1.54-2.61, p < 0.0001) and fully adjusted model (OR = 1.35, 95% CI: 1.03-1.77, p = 0.03)., Conclusions: MDS is positively associated with moderate/severe periodontitis. Further longitudinal studies are needed to understand the impact of MDS on periodontitis., (© 2024. The Author(s).)

Background: Decidualization is a critical step in establishing pregnancy in mammals. Successful decidualization depends on intricate gland-stromal crosstalk. Clusterin (Clu) is a ubiquitously secreted protein in physiological fluids that is involved in numerous physiological functions. However, the role of Clu in decidualization is not fully understood., Results: In this study, we examined the expression pattern of Clu during early pregnancy in mice and explored its potential function in decidualization. Our results revealed that Clu was expressed in the uterine glands on Days 1-2 of early pregnancy and on Days 5-8 during decidualization after embryo implantation, as well as in glands at the interimplantation site. Additionally, ovariectomized mice exhibited significant upregulation of Clu expression in the uterine glands 3 h after in vivo estrogen injection. Trem2, a receptor for Clu, was detected in the decidual region of mice on Days 5-8 of early pregnancy, where it mediates Clu to regulate the decidual region. Furthermore, we observed that recombinant CLU protein increased the expression of the decidualization marker molecules insulin-like growth factor binding protein 1 (IGFBP1) and prolactin (PRL) in decidual cells. However, this upregulation was not observed when Trem2 expression was inhibited with siRNA., Conclusions: Uterine gland-derived Clu, a new paracrine modulator, may participate in early pregnancy by influencing the decidualization process mediated by Trem2 in mice., (© 2024. The Author(s).)

Objective: This study aimed to evaluate the efficacy of autologous blood preparations, namely Platelet-Rich Plasma (PRP), Platelet-Rich Fibrin (PRF), and Concentrated Growth Factor (CGF), in maxillary sinus floor elevation surgery. The focus was on their impact on new bone formation, maxillary sinus floor height, and soft tissue healing., Methods: A systematic search was conducted across PubMed/MEDLINE, Web of Science, Embase, and Scopus databases up to April 2024. This systematic review included both randomized clinical trials (RCTs) and controlled clinical trials (CCTs) that evaluated the efficacy of autologous blood preparations in maxillary sinus floor elevation surgery. The primary outcomes measured were the percentage of new bone formation, maxillary sinus floor height, and he percentage of soft tissue area. Data from the selected studies were extracted and analyzed to determine the impact of autologous blood preparations on these outcomes. The risk of bias was assessed using Cochrane's risk of bias tool and ROBINS-I, and meta-analyses were performed using Review Manager 5.4 software to calculate effect sizes and integrate results from multiple studies., Results: Among the 507 screened articles, 30 studies met the inclusion criteria. The results indicated that the application of PRP significantly increased new bone formation during maxillary sinus floor elevation surgery (primary outcome, MD = 4.40, CI = 0.37 to 8.44, P = 0.03), as well as improving maxillary sinus floor height elevation (secondary outcome, MD = 1.00, CI = 0.78 to 1.23, P < 0.00001). The absence of PRP during surgery had a statistically significant effect on the percentage of soft tissue area (secondary outcome, MD= -5.25, CI= -7.29 to 3.20, P < 0.00001). However, based on the research findings, PRF did not show significant effects on enhancing new bone formation, maxillary sinus floor height elevation, and promoting soft tissue regeneration., Conclusions: PRP demonstrates efficacy in maxillary sinus floor elevation surgery by enhancing new bone formation and increasing sinus height. Further studies are needed to validate the outcomes of PRF and CGF., (© 2024. The Author(s).)

Background: Chronic alcohol users often exhibit an increased minimum alveolar concentration (MAC) of sevoflurane, yet the specific mechanism remains unclear. It has been reported that ethanol exposure can upregulate the protein expression and enzyme activity of cytochrome P450 2E1 (CYP2E1). CYP2E1 is a key enzyme that converts 2-5% of sevoflurane into equimolar amounts of hexafluoroisopropanol (HFIP) and F - . This study aims to explore whether ethanol exposure could alter sevoflurane metabolism through CYP2E1 modulation, potentially explaining the increased MAC observed in alcohol users., Methods: Eighty adult male Sprague-Dawley (SD) rats were randomly divided into two groups and received either 50% ethanol (dose: 3 g/kg) or 0.9% saline twice daily by gavage. After 1, 2, 3, and 4 weeks of gavage, ten rats were randomly selected from each group to undergo 1-hour anesthesia with 2.3% sevoflurane. Blood samples were collected after anesthesia to measure the concentration of free HFIP using gas chromatography. Additionally, the left lobe tissue of the liver was collected for the analysis of CYP2E1 protein expression by Western blot and CYP2E1 enzyme activity by colorimetric assay. Correlations between these parameters were analyzed using Pearson's correlation., Results: In the ethanol group, CYP2E1 expression, activity, and the concentration of free HFIP were significantly higher at all time points compared to the control group (P < 0.05), except for protein expression in the first week (P > 0.05). Within-group comparisons indicated no significant changes in any of the parameters for the control group (P > 0.05). In the ethanol group, there was no difference in free HFIP concentration between the first and second weeks (P > 0.05), but a significant increase was observed in the third and fourth weeks (P < 0.01); protein expression and enzyme activity significantly varied over time, especially showing a notable increase from the first to the third and fourth weeks (P < 0.05). Correlation analysis revealed strong positive correlations between free HFIP concentration and CYP2E1 activity (r = 0.7898), free HFIP concentration and CYP2E1 expression (r = 0.8418), and CYP2E1 activity and expression (r = 0.8740), all with P < 0.001., Conclusions: Ethanol exposure increased both the expression and enzymatic activity of CYP2E1, consequently enhancing the metabolism of sevoflurane., (© 2024. The Author(s).)

Background: Postpartum depression (PPD) has received widespread attention. Shenzhen has been running a large-scale program for PPD since 2013. The program requires mothers to self-assess when applying information technology to PPD screening beginning in 2021. The purpose of this study was to conduct a longitudinal analysis of the impact of mHealth apps on the health-seeking behaviors of PPD patients., Methods: Longitudinal data from districts in the Shenzhen Maternal and Child Health Management Information System (MCHMIS) for ten years was used in this study. Referral success rate (RSR, successful referrals to designated hospitals as a percentage of needed referrals) was used to assess health-seeking behavior. Trend χ2 tests were used to assess the overall trend of change after the implementation of mHealth in ten districts in Shenzhen. Interrupted Time Series Analysis (ITSA) was employed to assess the role of the mHealth app in changing patient health-seeking behaviors., Results: For the results of the trend χ2 tests, the ten districts of Shenzhen showed an upward trend. For the ITSA results, different results were shown between districts. Nanshan district, Longhua district, and Longgang district all demonstrated an upward trend in the first-year application of the mHealth app. Nanshan district and Longgang district both exhibited an upward trend in terms of sustained effects., Conclusions: There is a difference in the performance of the mHealth app across the ten districts. The results show that the three districts with better health resource allocation, Nanshan, Longgang, and Longhua districts, demonstrated more significant mHealth app improvements. The mHealth app's functions, management systems, and health resource allocation may be potential factors in the results. This suggests that when leveraging mHealth applications, the first step is to focus on macro-level area resource allocation measures. Secondly, there should be effective process design and strict regulatory measures. Finally, there should also be appropriate means of publicity., (© 2024. The Author(s).)

Objective: The fragility index (FI), which is the minimum number of changes in status from "event" to "non-event" resulting in a loss of statistical significance, serves as a significant supplementary indicator for clinical physicians in interpreting clinical trial results and aids in understanding the outcomes of randomized controlled trials (RCTs). In this systematic literature survey, we evaluated the FI for RCTs evaluating Chinese herbal medicine (CHM) for irritable bowel syndrome (IBS), and explored potential associations between study characteristics and the robustness of RCTs., Methods: A comprehensive search was conducted in four databases in Chinese and four databases in English from their inception to January 1, 2023. RCTs encompassed 1:1 ratio into two parallel arms and reported at least one binary outcome that demonstrated statistical significance were included. FI was calculated by the iterative reduction of a target outcome event in the treatment group and concomitant subtraction of a non-target event from that group, until positive significance (defined as P < 0.05 by Fisher's exact test) is lost. The lower the FI (minimum 1) of a trial outcome, the more fragile the positive result of the outcome was. Linear regression models were adopted to explore influence factors of the value of FI., Results: A total of 30 trials from 2 4118 potentially relevant citations were finally included. The median FI of total trials included was 1.5 (interquartile range [IQR], 1-5), and half of the trials (n = 15) had a FI equal to 1. In 12 trials (40%), the total number of participants lost to follow-up surpassed the respective FI. The study also identified that increased FI was significantly associated with no TCM syndrome differentiation for inclusion criteria of the patients, larger total sample size, low risk of bias, and larger numbers of events., Conclusions: The majority of CHM IBS RCTs with positive results were found to be fragile. Ensuring adequate sample size, scientifically rigorous study design, proper control of confounding factors, and a quality control calibration for consistency of TCM diagnostic results among clinicians should be addressed to increase the robustness of the RCTs. We recommend reporting the FI as one of the components of sensitivity analysis in future RCTs to facilitate the assessment of the fragility of trials., (© 2024. The Author(s).)

Background: Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases. Oleanolic acid (OA) is a pentacyclic triterpene that is ubiquitous in plants. Our previous work demonstrated the protective effect of OA on intestinal health, but the underlying molecular mechanisms remain unclear. This study investigated whether dietary supplementation with OA can prevent diarrhea and intestinal immune dysregulation caused by enterotoxigenic Escherichia coli (ETEC) in piglets. The key molecular role of bile acid receptor signaling in this process has also been explored., Results: Our results demonstrated that OA supplementation alleviated the disturbance of bile acid metabolism in ETEC-infected piglets (P < 0.05). OA supplementation stabilized the composition of the bile acid pool in piglets by regulating the enterohepatic circulation of bile acids and significantly increased the contents of UDCA and CDCA in the ileum and cecum (P < 0.05). This may also explain why OA can maintain the stability of the intestinal microbiota structure in ETEC-challenged piglets. In addition, as a natural ligand of bile acid receptors, OA can reduce the severity of intestinal inflammation and enhance the strength of intestinal epithelial cell antimicrobial programs through the bile acid receptors TGR5 and FXR (P < 0.05). Specifically, OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream cAMP-PKA-CREB signaling pathway (P < 0.05). Furthermore, OA enhanced CDCA-mediated MEK-ERK signaling in intestinal epithelial cells by upregulating the expression of FXR (P < 0.05), thereby upregulating the expression of endogenous defense molecules in intestinal epithelial cells., Conclusions: In conclusion, our findings suggest that OA-mediated regulation of bile acid metabolism plays an important role in the innate immune response, which provides a new diet-based intervention for intestinal diseases caused by pathogenic bacterial infections in piglets., (© 2024. The Author(s).)

Background: Macrophages are key inflammatory immune cells that orchestrate the initiation and progression of autoimmune diseases. The characters of macrophage in diseases are determined by its phenotype in response to the local microenvironment. Ficolins have been confirmed as crucial contributors to autoimmune diseases, with Ficolin-2 being particularly elevated in patients with autoimmune diseases. However, whether Ficolin-A stimulates macrophage polarization is still poorly understood., Methods: We investigated the transcriptomic expression profile of murine bone marrow-derived macrophages (BMDMs) stimulated with Ficolin-A using RNA-sequencing. To further confirm a distinct phenotype activated by Ficolin-A, quantitative RT-PCR and Luminex assay were performed in this study. Additionally, we assessed the activation of underlying cell signaling pathways triggered by Ficolin-A. Finally, the impact of Ficolin-A on macrophages were investigated in vivo through building Collagen-induced arthritis (CIA) and Dextran Sulfate Sodium Salt (DSS)-induced colitis mouse models with Fcna-/- mice., Results: Ficolin-A activated macrophages into a pro-inflammatory phenotype distinct to LPS-, IFN-γ- and IFN-γ + LPS-induced phenotypes. The transcriptomic profile induced by Ficolin-A was primarily characterized by upregulation of interleukins, chemokines, iNOS, and Arginase 1, along with downregulation of CD86 and CD206, setting it apart from the M1 and M2 phenotypes. The activation effect of Ficolin-A on macrophages deteriorated the symptoms of CIA and DSS mouse models, and the deletion of Fcna significantly alleviated the severity of diseases in mice., Conclusion: Our work used transcriptomic analysis by RNA-Seq to investigate the impact of Ficolin-A on macrophage polarization. Our findings demonstrate that Ficolin-A induces a novel pro-inflammatory phenotype distinct to the phenotypes activated by LPS, IFN-γ and IFN-γ + LPS on macrophages., (© 2024. The Author(s).)

Severe acute pancreatitis (SAP) begins with premature activation of enzymes, promoted by the immune system, triggering a potential systemic inflammatory response that leads to organ failure with increased mortality and a bleak prognosis. Interleukin-22 (IL-22) is a cytokine that may have a significant role in SAP. IL-22, a member of the IL-10 cytokine family, has garnered growing interest owing to its potential tissue-protective properties. Recently, emerging research has revealed its specific effects on pancreatic diseases, particularly SAP. This paper provides a review of the latest knowledge on the role of IL-22 and its viability as a therapeutic target in SAP., (© 2024. The Author(s).)

Objective: To assess stress distribution in peri-implant bone and attachments of mandibular overdentures retained by small diameter implants, and to explore the impact of implant distribution on denture stability., Methods: Through three-dimensional Finite Element Analysis (3D FEA), four models were established: three models of a two mandibular implants retained overdenture (IOD) and one model of a conventional complete denture (CD). The three IOD models consisted of one with two implants in the bilateral canine area, another with implants in the bilateral lateral incisor area, and the third with one implant in the canine area, and another in the lateral incisor area. Three types of loads were applied on the overdenture for each model: a 100 N vertical load and a inclined load on the left first molar, and a100N vertical load on the lower incisors. The stress distribution in the peri-implant bone, attachments, and the biomechanical behaviors of the overdentures were analyzed., Results: Despite different distribution of implants, the maximum stress values in peri-implant bone remained within the physiological threshold for all models across three loading conditions. The dispersed implant distribution design (implant in the canine area) exhibited the highest maximum stress in peri-implant bone (822.8 µe) and the attachments (275 MPa) among the three IOD models. The CD model demonstrated highest peak pressure on mucosa under three loading conditions (0.8188 Mpa). The contact area between the denture and mucosa of the CD model was smaller than that in the IOD models under molar loading, yet it was larger in the CD model compared to the IOD model under anterior loading. However, the contact area between the denture and mucosa under anterior loading in all models was significantly smaller than those under molar loading. The IOD in all three models exhibited significantly less rotational movement than the complete denture. Different implant positions had minimal impact on the rotational movement of the IOD., Conclusion: IOD with implants in canine area exhibited the highest maximum stress in the peri-implant bone and attachments, and demonstrated increased rotational movement. The maximum principal stress was concentrated around the neck of the small diameter one-piece implant, rather than in the abutment. An overdenture retained by two implants showed better stability than a complete denture., (© 2024. The Author(s).)

Objective: To develop and evaluate a deep learning model based on chest CT that achieves favorable performance on opportunistic osteoporosis screening using the lumbar 1 + lumbar 2 vertebral bodies fusion feature images, and explore the feasibility and effectiveness of the model based on the lumbar 1 vertebral body alone., Materials and Methods: The chest CT images of 1048 health check subjects from January 2021 to June were retrospectively collected as the internal dataset (the segmentation model: 548 for training, 100 for tuning and 400 for test. The classification model: 530 for training, 100 for validation and 418 for test set). The subjects were divided into three categories according to the quantitative CT measurements, namely, normal, osteopenia and osteoporosis. First, a deep learning-based segmentation model was constructed, and the dice similarity coefficient(DSC) was used to compare the consistency between the model and manual labelling. Then, two classification models were established, namely, (i) model 1 (fusion feature construction of lumbar vertebral bodies 1 and 2) and (ii) model 2 (feature construction of lumbar 1 alone). Receiver operating characteristic curves were used to evaluate the diagnostic efficacy of the models, and the Delong test was used to compare the areas under the curve., Results: When the number of images in the training set was 300, the DSC value was 0.951 ± 0.030 in the test set. The results showed that the model 1 diagnosing normal, osteopenia and osteoporosis achieved an AUC of 0.990, 0.952 and 0.980; the model 2 diagnosing normal, osteopenia and osteoporosis achieved an AUC of 0.983, 0.940 and 0.978. The Delong test showed that there was no significant difference in area under the curve (AUC) values between the osteopenia group and osteoporosis group (P = 0.210, 0.546), while the AUC value of normal model 2 was higher than that of model 1 (0.990 vs. 0.983, P = 0.033)., Conclusion: This study proposed a chest CT deep learning model that achieves favorable performance on opportunistic osteoporosis screening using the lumbar 1 + lumbar 2 vertebral bodies fusion feature images. We further constructed the comparable model based on the lumbar 1 vertebra alone which can shorten the scan length, reduce the radiation dose received by patients, and reduce the training cost of technologists., (© 2024. The Author(s).)

Background: Immune checkpoint inhibitors (ICIs) are commonly used in conjunction with chemotherapy to improve treatment outcomes for patients with gastric cancer. Since AFP could influence immunity by both inhibiting natural killer (NK) cells and regulating negatively the function of dendritic cells, we evaluated the influence of baseline serum alpha-fetoprotein (AFP) levels on the curative effect of ICIs in advanced gastric cancer (AGC) patients., Methods: A retrospective analysis was conducted on 158 AGC patients who underwent ICI treatment. The patients were divided into high and low groups based on the AFP threshold of 20 ng/ml. The efficacy of ICI treatment was assessed using objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS)., Results: The higher levels of baseline AFP were found to be associated with a decrease in the effectiveness of ICIs, as evidenced by a DCR of 50.0% in the group with high AFP levels compared to 87.7% in the group with low AFP levels (P < 0.001). Further analysis using Kaplan-Meier survival techniques indicated that a high AFP level was linked to shorter progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) in AGC individuals receiving ICIs. After propensity score matching, a log rank test revealed that the high AFP group had a decrease in median PFS (P = 0.011) and median OS (P = 0.036) compared to the low AFP group. The high AFP levels also showed its association with shorter PFS and OS in the subgroup analysis of ICI plus chemotherapy patients., Conclusions: Baseline AFP levels may predict immune checkpoint inhibitor treatment efficacy in AGC patients., (© 2024. The Author(s).)

Background: Exposure to ethylene oxide (EO) induces inflammation and oxidative stress, which are the main mechanisms of periodontitis. However, the effect of EO on periodontal health is not unclear. In this study, we aimed to explore the relationship between EO exposure and the risk of periodontitis in general US adults., Methods: Data used in our study from the National Health and Nutritional Examination Survey (NHANES) 2013-2014. The EO biomarker, hemoglobin adduct of EO (HbEO), was measured in blood samples utilizing high-performance liquid chromatography-tandem mass spectrometry. Periodontitis category was defined by the CDC/AAP according to clinical periodontal parameters. Natural cubic spline, weight multivariable logistic regression analyses and subgroup analysis were used to explore the association between EO exposure and the risk of periodontitis., Results: A total of 1497 participants over the age of 30 were included in our study. A non-linear positive association with periodontitis was identified for HbEO levels. Participants in the highest tertile of HbEO levels were more likely to have poorer periodontal health compared to the lowest tertile (OR tertile3vs1 = 2.80, 95% CI: 1.85-4.24). Similar results were also found in different subgroups., Conclusions: HbEO levels are positively associated with poor periodontal health in US adults. Additional longitudinal studies are necessary to further enhance our comprehension of the impact of exposure to EO on periodontal status., (© 2024. The Author(s).)

Background: The overall comprehensive consideration of the factors influencing the recommendations in the traditional Chinese medicine (TCM) guidelines remains poorly studied. This study systematically evaluate the factors influencing recommendations formation in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) clinical practice guidelines (CPGs) and TCM CPGs., Methods: This was a methodological review in which we searched six databases and multiple related websites. The GRADE CPGs were identified as the guidelines developed by the GRADE Working Group or the two Co-Chairs. For the TCM CPGs, we randomly selected guidelines that were published by the TCM or integrative medicine academic societies from China mainland (published by the TCM or integrative medicine academic societies of China mainland). Two reviewers independently screened and extracted data. We included CPGs published in 2018-2022. We extracted information on the influencing factors of evidence to recommendation and conducted the analyses using descriptive statistics and calculated the proportion of relevant items by IBM SPSS Statistics and Microsoft Excel to compare the differences between the GRADE CPGs and the TCM CPGs., Results: Forty-five GRADE CPGs (including 912 recommendations) and 88 TCM CPGs (including 2452 recommendations) were included. TCM recommendations mainly considered the four key determinants of desirable anticipated effects, undesirable anticipated effects, balance between desirable and undesirable effects, certainty of evidence, with less than 20% of other dimensions. And TCM CPGs presented more strong recommendations (for or against) and inappropriate discordant recommendations than GRADE CPGs. GRADE CPGs were more comprehensive considered about the factors affecting the recommendations, and considered more than 70% of all factors in the evidence to recommendation., Conclusions: The TCM CPGs lack a comprehensive consideration of multiple influencing determinants from evidence to recommendations. In the future, the correct application of the GRADE approaches should be emphasized., (© 2023. The Author(s).)

Background: Active hydrothermal vents create extreme conditions characterized by high temperatures, low pH levels, and elevated concentrations of heavy metals and other trace elements. These conditions support unique ecosystems where chemolithoautotrophs serve as primary producers. The steep temperature and pH gradients from the vent mouth to its periphery provide a wide range of microhabitats for these specialized microorganisms. However, their metabolic functions, adaptations in response to these gradients, and coping mechanisms under extreme conditions remain areas of limited knowledge. In this study, we conducted temperature gradient incubations of hydrothermal fluids from moderate (pH = 5.6) and extremely (pH = 2.2) acidic vents. Combining the DNA-stable isotope probing technique and subsequent metagenomics, we identified active chemolithoautotrophs under different temperature and pH conditions and analyzed their specific metabolic mechanisms., Results: We found that the carbon fixation activities of Nautiliales in vent fluids were significantly increased from 45 to 65 °C under moderately acidic condition, while their heat tolerance was reduced under extremely acidic conditions. In contrast, Campylobacterales actively fixed carbon under both moderately and extremely acidic conditions under 30 - 45 °C. Compared to Campylobacterales, Nautiliales were found to lack the Sox sulfur oxidation system and instead use NAD(H)-linked glutamate dehydrogenase to boost the reverse tricarboxylic acid (rTCA) cycle. Additionally, they exhibit a high genetic potential for high activity of cytochrome bd ubiquinol oxidase in oxygen respiration and hydrogen oxidation at high temperatures. In terms of high-temperature adaption, the rgy gene plays a critical role in Nautiliales by maintaining DNA stability at high temperature. Genes encoding proteins involved in proton export, including the membrane arm subunits of proton-pumping NADH: ubiquinone oxidoreductase, K + accumulation, selective transport of charged molecules, permease regulation, and formation of the permeability barrier of bacterial outer membranes, play essential roles in enabling Campylobacterales to adapt to extremely acidic conditions., Conclusions: Our study provides in-depth insights into how high temperature and low pH impact the metabolic processes of energy and main elements in chemolithoautotrophs living in hydrothermal ecosystems, as well as the mechanisms they use to adapt to the extreme hydrothermal conditions. Video Abstract., (© 2023. The Author(s).)

Background: Although exercise has been proposed as an effective intervention for various lifestyle-related diseases and pathological scenarios, few researches assessed the impact of taking exercise on the prevalence of periodontitis., Purpose: This study aimed to perform a comprehensive literature review and meta-analysis from both observational and intervention studies to explore the relationship between exercise and periodontitis and to provide references for future intervention programs aimed at preventing periodontitis., Method: A systematic literature search was conducted in PubMed/MEDLINE, Web of Science, Cochrane Library, and Scopus for peer-reviewed studies published in English From January 1993 to January 2023 according to the PRISMA guidelines. Articles were selected if subjects were human and studies evaluating the association between exercise and periodontitis., Results: 4098 references were retrieved. After screening the results, 30 studies were selected. Of these, 20 studies indicated an inverse association between exercise and periodontitis, while the remaining 10 did not reach conclusive findings. The meta-analysis demonstrated a risk ratio of 0.84 (95%CI: 0.77, 0.91) between the active group and the inactive group (P < 0.01), which indicated an inverse relationship between exercise and periodontitis., Conclusion: Overall, the increase in exercise presents an inverse association with the presence and severity of periodontitis. Accordingly, taking exercise might be a potential approach that contributes to improvements in periodontitis., (© 2023. The Author(s).)

Background: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes and the main cause of non-traumatic amputation, with no ideal treatment. Multiple cell-derived exosomes have been reported to improve the progression of DPN. Blood therapy is thought to have a powerful repairing effect. However, whether it could also improve DPN remains unclear., Results: In this study, we found that microRNA (miRNA) expression in plasma-derived exosomes of healthy rats (hplasma-exos) was significantly different from that of age-matched DPN rats. By injection of hplasma-exos into DPN rats, the mechanical sensitivity of DPN rats was decreased, the thermal sensitivity and motor ability were increased, and the nerve conduction speed was accelerated. Histological analysis showed myelin regeneration of the sciatic nerve, increased intraepidermal nerve fibers, distal local blood perfusion, and enhanced neuromuscular junction and muscle spindle innervation after hplasma-exos administration. Compared with plasma exosomes in DPN, miR-20b-3p was specifically enriched in exosomes of healthy plasma and was found to be re-upregulated in the sciatic nerve of DPN rats after hplasma-exos treatment. Moreover, miR-20b-3p agomir improved DPN symptoms to a level similar to hplasma-exos, both of which also alleviated autophagy impairment induced by high glucose in Schwann cells. Mechanistic studies found that miR-20b-3p targeted Stat3 and consequently reduced the amount of p-Stat3, which then negatively regulated autophagy processes and contributed to DPN improvement., Conclusions: This study demonstrated that miRNA of plasma exosomes was different between DPN and age-matched healthy rats. MiR-20b-3p was enriched in hplasma-exos, and both of them could alleviated DPN symptoms. MiR-20b-3p regulated autophagy of Schwann cells in pathological states by targeting Stat3 and thereby inhibited the progression of DPN., (© 2023. The Author(s).)

Luteolin is a flavonoid found in high concentrations in celery and green pepper, and acts as a neuroprotectant. PSMC5 (proteasome 26S subunit, ATPase 5) protein levels were reduced after luteolin stimulation in activated microglia. We aimed to determine whether regulating PSMC5 expression could inhibit neuroinflammation, and investigate the underlying mechanisms.BV2 microglia were transfected with siRNA PSMC5 before the addition of LPS (lipopolysaccharide, 1.0 µg/ml) for 24 h in serum free DMEM. A mouse model of LPS-induced cognitive and motor impairment was established to evaluate the neuroprotective effects of shRNA PSMC5. Intracerebroventricular administration of shRNA PSMC5 was commenced 7 days prior to i.p. injection of LPS (750 μg/kg). Treatments and behavioral experiments were performed once daily for 7 consecutive days. Behavioral tests and pathological/biochemical assays were performed to evaluate LPS-induced hippocampal damage. Molecular dynamics simulation was used to confirm the interaction between PSMC5 and TLR4 (Toll-like receptor 4) in LPS-stimulated BV2 microglia. SiRNA PSMC5 inhibited BV2 microglial activation, and suppressed the release of inflammatory factors (IL-1β, COX-2, PGE 2 , TNF-α, and iNOS) upon after LPS stimulation in BV2 microglia. LPS increased IκB-α and p65 phosphorylation, which was attenuated by siRNA PSMC5. Behavioral tests and pathological/biochemical assays showed that shRNA PSMC5 attenuated LPS-induced cognitive and motor impairments, and restored synaptic ultrastructure and protein levels in mice. ShRNA PSMC5 reduced pro-inflammatory cytokine (TNF-α, IL-1β, PGE 2 , and NO) levels in the serum and brain, and relevant protein factors (iNOS and COX-2) in the brain. Furthermore, shRNA PSMC5 upregulated the anti-inflammatory mediators interleukin IL-4 and IL-10 in the serum and brain, and promoted a pro-inflammation-to-anti-inflammation phenotype shift in microglial polarization. Mechanistically, shRNA PSMC5 significantly alleviated LPS-induced TLR4 expression. The polarization of LPS-induced microglial pro-inflammation phenotype was abolished by TLR4 inhibitor and in the TLR-4 -/- mouse, as in shRNA PSMC5 treatment. PSMC5 interacted with TLR4 via the amino sites Glu284, Met139, Leu127, and Phe283. PSMC5 site mutations attenuated neuroinflammation and reduced pro-inflammatory factors by reducing TLR4-related effects, thereby reducing TLR4-mediated MyD88 (myeloid differentiation factor 88)-dependent activation of NF-κB. PSMC5 could be an important therapeutic target for treatment of neurodegenerative diseases involving neuroinflammation-associated cognitive deficits and motor impairments induced by microglial activation., (© 2023. The Author(s).)

Background: Emerging evidence has shown that extracellular vesicles (EVs) derived from gut bacteria play a crucial role in microbiota-host interactions. Here, we aimed to evaluate the attenuating effect of EVs derived from a reduced commensal bacterium, F. prausnitzii (Fp-EVs), in inflammatory bowel disease (IBD) on dextran sulfate sodium (DSS)-induced colitis in mice., Results: Fp-EVs isolated by ultracentrifugation and typically exhibited a double concave disc shape with an average diameter of 172 nm. Fp-EVs treatment reduced DSS-induced weight loss, disease activity index (DAI) score, colon length shortening, histological damage, neutrophil infiltration and increased intestinal epithelial apoptotic cells in DSS-induced colitis mice. Fp-EVs upregulated the protein expression of zona occludens (ZO)-1 and Occludin and increased the ratio of Tregs in the colon tissue of colitis mice. Furthermore, Fp-EVs downregulated the expression of the proinflammatory cytokines interleukin-1β (IL-1β), IL-2, IL-6, IL-12a, IL-17a, Interferon-γ (IFN-γ), tumor necrosis factor - α (TNF-α), granulocyte-macrophage colony stimulating factor (GM-CSF) and upregulated the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor β (TGF-β) in DSS-treated mice. Moreover, Fp-EV treatment markedly reduced the phosphorylation of these proteins Nuclear factor-κB (NF-κB) and Mitogen activated protein kinase (MAPK), and regulated the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1)., Conclusion: Our findings revealed that Fp-EVs attenuated DSS-induced colitis by modulating the intestinal mucosal barrier function and immunological profile. Our findings reveal that Fp-EVs attenuate DSS-induced colitis by modulating intestinal mucosal barrier function and the immunological profile., (© 2023. The Author(s).)

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by ovarian cysts, high androgen levels, and irregular menstruation. The causality between PCOS and breast cancer (BC) has been widely discussed as they share a significant intersection in clinical manifestations. Previous epidemiological studies have not provided consistent conclusions in association between PCOS and BC, while mendelian randomization (MR) analyses have confirmed the causality between PCOS and estrogen receptor-positive breast cancer (ER + BC), but among a series of clinical manifestations resulting from PCOS, which related traits mediate the causal effect remains unknown. In this study, we conducted multivariable mendelian randomization (MVMR) analysis to explore the potential mediator variables in the mechanism linking PCOS to distinct subtypes of BC, and calculated the mediating effects proportion. We analyzed 13 PCOS-related traits and found that age at menopause may mediate PCOS-induced ER + BC (with -4.82% proportion) with a weak protective effect through the repair of DNA double-strand breaks by homologous recombination. This study helps to better comprehend the shared mechanisms contributing to the development of both PCOS and BC, and to screen high-risk populations for BC and take appropriate preventive measures., (© 2023. The Author(s).)

Background: Maintaining the repair phenotype of denervated Schwann cells in the injured distal nerve is crucial for promoting peripheral nerve regeneration. However, when chronically denervated, the capacity of Schwann cells to support repair and regeneration deteriorates, leading to peripheral nerve regeneration and poor functional recovery. Herein, we investigated whether neurotrophin-3 (NT-3) could sustain the reparative phenotype of Schwann cells and promote peripheral nerve regeneration after chronic denervation and aimed to uncover its potential molecular mechanisms., Methods: Western blot was employed to investigate the relationship between the expression of c-Jun and the reparative phenotype of Schwann cells. The inducible expression of c-Jun by NT-3 was examined both in vitro and in vivo with western blot and immunofluorescence staining. A chronic denervation model was established to study the role of NT-3 in peripheral nerve regeneration. The number of regenerated distal axons, myelination of regenerated axons, reinnervation of neuromuscular junctions, and muscle fiber diameters of target muscles were used to evaluate peripheral nerve regeneration by immunofluorescence staining, transmission electron microscopy (TEM), and hematoxylin and eosin (H&E) staining. Adeno-associated virus (AAV) 2/9 carrying shRNA, small molecule inhibitors, and siRNA were employed to investigate whether NT-3 could signal through the TrkC/ERK pathway to maintain c-Jun expression and promote peripheral nerve regeneration after chronic denervation., Results: After peripheral nerve injury, c-Jun expression progressively increased until week 5 and then began to decrease in the distal nerve following denervation. NT-3 upregulated the expression of c-Jun in denervated Schwann cells, both in vitro and in vivo. NT-3 promoted peripheral nerve regeneration after chronic denervation, mainly by upregulating or maintaining a high level of c-Jun rather than NT-3 itself. The TrkC receptor was consistently presented on denervated Schwann cells and served as NT-3 receptors following chronic denervation. NT-3 mainly upregulated c-Jun through the TrkC/ERK pathway., Conclusion: NT-3 promotes peripheral nerve regeneration by maintaining the repair phenotype of Schwann cells after chronic denervation via the TrkC/ERK/c-Jun pathway. It provides a potential target for the clinical treatment of peripheral nerve injury after chronic denervation., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Physical activity and eating behavior are associated with hypertension in children and adolescents. Revealing the associations between physical activity patterns, eating behavior patterns and high blood pressure (HBP) could help improve the problem of hypertension from the actual children's physical activities and eating behaviors., Methods: A total of 687 students aged 8-15 years were selected from two nine-year primary and secondary schools using stratified cluster random sampling method. The students' body height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured, and their physical activity time and eating behaviors were surveyed by using CLASS questionnaire and self-made eating behavior questionnaire, respectively. Exploratory factor analysis (EFA) was used to extract moderate to vigorous physical activity factor (MVPAF), sedentary activity factor (SAF), healthy eating behavior factor (HEBF), unhealthy eating behavior factor (UHEBF). MVPAF ≥ SAF was defined as moderate to vigorous physical activity pattern (MVPAP), MVPAF < SAF was defined as sedentary activity pattern (SAP). HEBF ≥ UHEBF was defined as healthy eating behavior pattern (HEBP), while the opposite was defined as unhealthy eating behavior pattern (UHEBP). Lifestyles includes physical activity patterns and eating behavior patterns., Results: The overall prevalence of hypertension was 5.8% (40/687), and was 5.69% (21/369) in boys and 5.97% (19/318) in girls, respectively. The MVPAF and UHEBF in boys were significantly higher than those in girls (P < 0.01), while the SAF in girls was significantly higher than that in boys (P < 0.05). The SAF was positively correlated with SBP in girls (β(SE) = 0.14 (0.50), P = 0.016), and was positively correlated with SBP (β(SE) = 0.21 (1.22), P = 0.000 and DBP (β(SE) = 0.14 (0.49), P = 0.006) in boys. The MVPAF was negatively correlated with DBP (β(SE)=-0.11 (0.40), P = 0.022) in boys. In boys, the SAP increased the risks of HBP (OR (95% CI):3.34 (1.30-8.63)) and high DBP (OR (95% CI):3.08 (1.02-9.34)) compared with MVPAP., Conclusion: Compared with the boys with MVPAP, boys with SAP may increase the risks of HBP and high DBP. The SAF may be positively associated with SBP in boys and girls, while the MVPAF may be negatively associated with DBP in boys., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: To investigate the impact of the coronavirus disease 2019 (COVID-19) outbreak on the prevalence of respiratory viruses among pediatric patients with acute respiratory infections in Xuzhou from 2015-2021., Methods: Severe acute respiratory infection (SARI) cases in hospitalized children were collected from 2015-2021 in Xuzhou, China. Influenza virus(IFV), respiratory syncytial virus (RSV), human parainfluenza virus type 3(hPIV-3), human rhinovirus (hRV), human adenovirus(hAdV), human coronavirus(hCoV) were detected by real-time fluorescence polymerase chain reaction(RT-qPCR), and the results were statistically analyzed by SPSS 23.0 software., Results: A total of 1663 samples with SARI were collected from 2015-2021, with a male-to-female ratio of 1.67:1 and a total virus detection rate of 38.5% (641/1663). The total detection rate of respiratory viruses decreased from 46.2% (2015-2019) to 36% (2020-2021) under the control measures for COVID-19 (P < 0.01). The three viruses with the highest detection rates changed from hRV, RSV, and hPIV-3 to hRV, RSV, and hCoV. The epidemic trend of hPIV-3 and hAdV was upside down before and after control measures(P < 0.01); however, the epidemic trend of RV and RSV had not changed from 2015 to 2021(P > 0.05). After the control measures, the detection rate of hPIV-3 decreased in all age groups, and the detection rate of hCoV increased in all except the 1 ~ 3 years old group., Conclusions: Implementing control measures for COVID-19 outbreak curbed the spread of respiratory viruses among children as a whole. However, the epidemic of RV and RSV was not affected by the COVID-19 control policy., (© 2023. The Author(s).)

Background: Within 3 years of the COVID-19 pandemic, increasing interest has been given to its potential influence on health status due to lockdowns caused by the pandemic. However, the impact is inadequately understood, especially for college students. This study aimed to investigate the potential association between psychological stress, anxiety and oral health of college students during the Omicron wave of the COVID-19 pandemic., Methods: An online survey with measurements of psychological stress, anxiety and oral health was completed by 1770 Chinese college students. The Perceived Stress Scale-14 (PSS-14) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure psychological stress and anxiety, respectively. Oral health status was self-reported including toothache, gingival bleeding, and oral ulcer. Multivariable logistic regressions were performed to determine underlying associations for outcome variables. Structural equation modeling (SEM) was performed to confirm the relationship between mental and oral health status., Results: Of the 1770 subjects, 39.2% presented high psychological stress and only 41.2% expressed no anxiety. A significant association was found between psychological stress, anxiety and oral health status. Anxiety has significant impacts on toothache (OR = 0.36; 95%CI: 0.23-0.55; p < 0.01), gingival bleeding (OR = 0.43; 95%CI: 0.29-0.65; p < 0.01), and oral ulcer (OR = 0.54; 95%CI: 0.36-0.80; p < 0.01). Anxiety significantly mediated the association between psychological stress and self-reported oral symptoms., Conclusions: Anxiety may be a significant risk indicator for mental health among college students and demonstrates a significant relationship with the occurrence of self-reported oral symptoms. Concerns about academic and life changes caused by the pandemic were the two most significant sources of stress., (© 2023. The Author(s).)

Objective: The purpose of the present study was to determine the learning curve for a novel seven-axis robot-assisted (RA) total knee arthroplasty (TKA) system and to explore whether it could provide superior short-term clinical and radiological outcomes compared with conventional surgery., Methods: In the present retrospective study, 90 patients who underwent RA-TKA were included in robot-assisted system (RAS) group and 90 patients who underwent conventional TKA were included in the conventional group. The duration of surgery and robot-related complications were recorded to evaluate the learning curve through cumulative sum and risk-adjusted cumulative sum methods. The demographic data, preoperative clinical data, preoperative imaging data, duration of surgery, alignment of the prosthesis, lower limb force line alignment, Knee Society score, 10-cm visual analog scale pain score and range of motion were compared between the RAS and conventional groups. In addition, the proficiency group was compared with the conventional group using propensity score matching., Results: RA-TKA was associated with a learning curve of 20 cases for the duration of surgery. There was no significant difference in indicators representing the accuracy of the prosthetic installation between the learning and proficiency phases in RA-TKA group patients. A total of 49 patients in the proficiency group were matched with 49 patients from the conventional group. The number of postoperative hip-knee-ankle (HKA) angle, component femoral coronal angle (CFCA), component tibial coronal angle (CTCA), and sagittal tibial component angle (STCA) outliers in the proficiency phase was lower than that in the conventional group, while deviations of the HKA angle, CFCA, CTCA, and STCA in the proficiency phase were significantly lower than those in the conventional group (P < 0.05)., Conclusion: In summary, from the learning curve data, 20 cases are required for a surgeon using a novel seven-axis RA-TKA system to enter the proficiency phase. In the proficiency group, compared with the conventional group using propensity score matching, the RAS was found to be superior to the conventional group in prosthesis and lower limb alignment., (© 2023. The Author(s).)

Objective: The aim of this study was to search for key genes in ankylosing spondylitis (AS) through comprehensive bioinformatics analysis, thus providing some theoretical support for future diagnosis and treatment of AS and further research., Methods: Gene expression profiles were collected from Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/ ) by searching for the term "ankylosing spondylitis". Ultimately, two microarray datasets (GSE73754 and GSE11886) were downloaded from the GEO database. A bioinformatic approach was used to screen differentially expressed genes and perform functional enrichment analysis to obtain biological functions and signalling pathways associated with the disease. Weighted correlation network analysis (WGCNA) was used to further obtain key genes. Immune infiltration analysis was performed using the CIBERSORT algorithm to conduct a correlation analysis of key genes with immune cells. The GWAS data of AS were analysed to identify the pathogenic regions of key genes in AS. Finally, potential therapeutic agents for AS were predicted using these key genes., Results: A total of 7 potential biomarkers were identified: DYSF, BASP1, PYGL, SPI1, C5AR1, ANPEP and SORL1. ROC curves showed good prediction for each gene. T cell, CD4 naïve cell, and neutrophil levels were significantly higher in the disease group than in the paired normal group, and key gene expression was strongly correlated with immune cells. CMap results showed that the expression profiles of ibuprofen, forskolin, bongkrek-acid, and cimaterol showed the most significant negative correlation with the expression profiles of disease perturbations, suggesting that these drugs may play a role in AS treatment., Conclusion: The potential biomarkers of AS screened in this study are closely related to the level of immune cell infiltration and play an important role in the immune microenvironment. This may provide help in the clinical diagnosis and treatment of AS and provide new ideas for further research., (© 2023. The Author(s).)

Background: To compare the accuracy of dental implant placement using a novel dental implant robotic system (THETA) and a dynamic navigation system (Yizhimei) by a vitro model experiment., Methods: 10 partially edentulous jaws models were included in this study, and 20 sites were randomly assigned into two groups: the dental implant robotic system (THETA) group and a dynamic navigation system (Yizhimei) group. 20 implants were placed in the defects according to each manufacturer's protocol respectively. The implant platform, apex and angle deviations were measured by fusion of the preoperative design and the actual postoperative cone-beam computed tomography (CBCT) using 3D Slicer software. Data were analyzed by t - test and Mann-Whitney U test, p < 0.05 was considered statistically significant., Results: A total of 20 implants were placed in 10 phantoms. The comparison deviation of implant platform, apex and angulation in THETA group were 0.58 ± 0.31 mm, 0.69 ± 0.28 mm, and 1.08 ± 0.66 ° respectively, while in Yizhimei group, the comparison deviation of implant platform, apex and angulation were 0.73 ± 0.20 mm, 0.86 ± 0.33 mm, and 2.32 ± 0.71 ° respectively. The angulation deviation in THETA group was significantly smaller than the Yizhimei group, and there was no significant difference in the deviation of the platform and apex of the implants placed using THETA and Yizhimei, respectively., Conclusion: The implant positioning accuracy of the robotic system, especially the angular deviation was superior to that of the dynamic navigation system, suggesting that the THETA robotic system could be a promising tool in dental implant surgery in the future. Further clinical studies are needed to evaluate the current results., (© 2023. The Author(s).)

Background: Inflammation and oxidative stress are two hallmarks of periodontitis. Retinol is an antioxidant and suppresses expression of pro-inflammatory factors. However, the evidence for an association between retinol intake and periodontitis is limited. Thus, the aim of this study is to assess the association between retinol intake and periodontal health., Methods: Data used in this cross-sectional study from the National Health and Nutrition Examination Survey (NHANES) 2009-2014 (n = 9081). Dietary intake of retinol was measured based on two 24-h dietary recall interviews. The category of periodontitis was defined by the CDC/AAP according to clinical periodontal parameters. Univariate and multivariate logistic regression analyses were applied to investigate the relationship between retinol intake and the risk of periodontitis., Results: Compared with the lowest tertile, individuals in the highest tertile of retinol intake were less likely to be periodontitis (OR tertile3vs1  = 0.79, 95% CI: 0.65-0.96). The association was still significant in populations who were less than 60 years old (OR tertile3vs1  = 0.80, 95% CI: 0.65-0.97), non-Hispanic black (OR tertile3vs1  = 0.62, 95% CI: 0.42-0.94), PI ≤ 1.3 (OR tertile3vs1  = 0.72, 95% CI: 0.55-0.93), 1.3 < PI ≤ 3.5 (OR tertile3vs1  = 0.70, 95% CI: 0.55-0.89), non-smoker (OR tertile3vs1  = 0.63, 95% CI: 0.48-0.81), obesity (OR tertile3vs1  = 0.68, 95% CI: 0.49-0.94) and who had not diabetes mellitus (OR tertile3vs1  = 0.79, 95% CI: 0.65-0.95) or had hypertension (OR tertile3vs1  = 0.63, 95% CI: 0.47-0.84)., Conclusion: Retinol intake is inversely associated with poor periodontal health in US adults., (© 2023. The Author(s).)

Background: Quadratus lumborum block was recently proposed as an alternative technique for post-cesarean delivery analgesia. However, there is not a definite optimum concentration of local anesthetics. A biased coin design up-and-down method was used to explore the minimum effective concentration of ropivacaine in quadratus lumborum block for satisfactory analgesia after cesarean delivery., Methods: Fifty-six patients weighing 60-80 kg after cesarean section and with ages between 18 and 40 years were recruited. For the posterior quadratus lumborum block, a volume of 25 ml of the assigned concentration of ropivacaine was injected bilaterally. The concentration administered to each patient depended on the response to the previous dose. The first patient received 0.25%. If a successful block was observed, the next patient was randomized to receive the same ropivacaine concentration (with a probability of 0.89) or 0.025% less (with a probability of 0.11). After any block failure, the concentration was always increased by 0.025% for the next. The study ended when 45 successful blocks were obtained. We defined effective quadratus lumborum block as a resting visual analog score ≤ 3 and the absence of a need for rescue anesthetics., Results: The 90% minimum effective concentration of ropivacaine was 0.335% (95% CI 0.306 to 0.375%), and the 99% minimum effective concentration was 0.371% (95% CI 0.355 to 0.375%). The sufentanil consumption was 11 (11,13) and 24 (22,27) μg at 12 and 24 hours after quadratus lumborum block, respectively., Conclusions: The optimum dosage of ropivacaine is a 25 ml volume of 0.335% for quadratus lumborum block after cesarean delivery., Trial Registration: The study was registered in the Chinese Clinical Trial Registry (No. ChiCTR2000040415 )., (© 2022. The Author(s).)

Background: To comprehensively analyze the stemness characteristics related to prognosis and the immune microenvironment in lung adenocarcinoma (LUAD)., Methods: The OCLR machine learning method was used to calculate the stemness index (mRNAsi) of the LUAD samples. DEGs common between the low mRNAsi, normal, and high mRNAsi groups were screened and the immune-stemness genes were obtained. Then the PPI network was created and enrichment analyses were performed. Moreover, different subtypes based on immune-stemness genes associated with prognosis were identified, and the relationships between LUAD stemness and TIME variables were systematically analyzed, followed by TMB analysis., Results: Patients in the high mRNAsi groups with poor prognosis were screened along with 144 immune-stemness genes. IL-6, FPR2, and RLN3 showed a higher degree in the PPI network. A total of 26 immune-stemness genes associated with prognosis were screened. Two clusters were obtained (cluster 1 and cluster 2). Survival analysis revealed that patients in cluster 2 had a poor prognosis. A total of 12 immune cell subpopulations exhibited significant differences between cluster 1 and cluster 2 (P < 0.05). A total of 10 immune checkpoint genes exhibited significantly higher expression in cluster 1 (P < 0.05) than in cluster 2. Further, the TMB value in cluster 2 was higher than that in cluster 1 (P < 0.05)., Conclusion: Immune-stemness genes, including L-6, FPR2, and RLN3, might play significant roles in LUAD development via cytokine-cytokine receptor interaction, neuroactive ligand‒receptor interaction, and the JAK‒STAT pathway. Immune-stemness genes were related to tumor-infiltrating immune cells, TMB, and expression of immune checkpoint gene., (© 2022. The Author(s).)

Background: Norovirus is highly diverse and constant surveillance is essential for the prevention and control of norovirus gastroenteritis., Methods: From 2015 to 2019, fecal samples were collected from sporadic cases and outbreaks of acute gastroenteritis reported to Sichuan center for disease control and prevention. Sewage samples were collected from a wastewater treatment plant in Sichuan. All samples were tested for norovirus by real-time reverse transcription polymerase chain reaction. Norovirus-positive clinical samples were sequenced by Sanger sequencing. Sewage samples were sequenced by amplicon and virome sequencing., Results: A total of 1462 fecal samples were collected and 11 different norovirus genotypes were detected. GII.4 Sydney 2012[P31] and GII.3[P12] were the dominant genotypes in sporadic cases whereas GII.2[P16] and GII.17[P17] were the dominant genotypes in outbreaks. GII.3 was predominant in children 0-6 months of age during spring and summer, while GII.4 was predominant in children older than 6 months and in the autumn. The detection rate of GII.17[P17] increased with age. In sewage, 16 genotypes were detected. GII.3, GII.4, GI.1, and GI.2 were the dominant genotypes., Conclusion: This study demonstrated that multiple norovirus genotypes co-circulate in Sichuan. It is vital to continuously trace the genetic diversity of norovirus to give a future perspective on surveillance needs and guide vaccine design and policy decisions., (© 2022. The Author(s).)

Background: Exosome mediated mRNA delivery is a promising strategy for the treatment of multiple diseases. However, the low yield of exosomes is a bottleneck for clinical translation. In this study, we boosted exosome production via simultaneously reducing the expression of genes inhibiting exosome biogenesis and supplementing the culture medium with red cell membrane components., Results: Among the candidate genes, knocking down of Rab4 was identified to have the highest efficacy in promoting exosome biogenesis while without any obvious cytotoxicity. Additionally, supplementing red cell membrane particles (RCMPs) in the culture medium further promoted exosome production. Combination of Rab4 knockdown and RCMP supplement increased exosome yield up to 14-fold. As a proof-of-concept study, low-density lipoprotein receptor (Ldlr) mRNA was forced expressed in the exosome donor cells and passively encapsulated into the exosomes during biogenesis with this strategy. Though exosome production per cell increased, the booster strategy didn't alter the loading efficiency of therapeutic Ldlr mRNA per exosome. Consistently, the therapeutic exosomes derived by the strategy alleviated liver steatosis and atherosclerosis in Ldlr -/- mice, similar as the exosomes produced by routine methods., Conclusions: Together, the proposed exosome booster strategy conquers the low yield bottleneck to some extent and would certainly facilitate the clinical translation of exosomes., (© 2022. The Author(s).)

Background: Salt stress is one of the most destructive environmental factors limiting crop growth and development. MicroRNAs (miRNAs) are a class of conserved endogenous small non-coding RNAs, playing the crucial role in regulating salt response and tolerance in plants. However, the miRNAs in wild emmer wheat, especially the key and specific salt-responsive miRNAs are not well studied., Results: Here, we performed small RNA, transcriptome, and degradome sequencing of both of salt-tolerance (ST) and salt-sensitive (SS) wild emmer genotypes to identify the miRNA-mRNA modules associating with salt tolerance. Totally, 775 miRNAs, including 361 conserved known miRNAs and 414 novel miRNAs were detected. Differential expression analysis identified 93 salt-responsive miRNAs under salt stress. Combined with RNA-seq and degradome sequencing analysis, 224 miRNA-mRNA modules displayed the complete opposite expression trends between ST and SS genotypes, most of which functionally enriched into ROS homeostasis maintaining, osmotic pressure modulating, and root growth and development. Finally, the qRT-PCR and a large-scale yeast functional screening were also performed to initially validate the expression pattern and function of candidate genes., Conclusions: This study reported the key and specific miRNA-mRNA modules associated with salt tolerance in wild emmer, which lay the foundation for improving the salt tolerance in cultivated emmer and bread wheat through miRNA engineering approach., (© 2022. The Author(s).)

Background: During cataract phacoemulsification surgery, an Intrepid® balanced (IB) tip can achieve a larger amplitude, which may lead to higher energy efficiency than a Kelman (K) tip when paired with a torsional phaco platform. In this retrospective cohort study, we compared their energy efficiency and damage to the cornea under a new energy setting., Methods: The medical records of 104 eyes of 79 patients were reviewed, with 47 eyes belonging to the IB group and 57 eyes belonging to the K group. All surgeries were performed on an Alcon Centurion® platform with gravity infiltration. Surgical parameters, visual outcome, central corneal thickness (CCT) changes, and endothelial cell density (ECD) loss rate were recorded and calculated., Results: No significant differences in postoperative best corrected visual acuity (BCVA), intraocular pressure (IOP), total ultrasound time, estimated fluid aspirated, CCT changes, or ECD loss rate were observed between the two groups. We divided the included eyes into soft nucleus and hard nucleus subgroups and found lower cumulative dissipated energy (CDE, 8.15 ± 8.02 vs 14.82 ± 14.16, P = 0.023), cumulative torsional energy (CTE, 8.06 ± 7.87 vs 14.13 ± 13.02, P = 0.027), and cumulative longitudinal energy (CLE, 0.09 ± 0.17 vs 0.69 ± 1.37, P = 0.017) in the IB group than in the K group, implying less energy used and higher energy efficiency of the IB tip., Conclusion: Lower CLE in the IB group indicates fewer phaco tip obstructions and a significantly higher capability to conquer hard nuclei with IB tips with statistical significance. With an ultra-perfusion cannula, the balanced tip does not cause more corneal damage., (© 2022. The Author(s).)

Background: A precise evaluation of liver reserve function in patients with hepatic alveolar echinococcosis (HAE) prior to hepatectomy could substantially increase the success rate of the operation and reduce the incidence of postoperative complications. The present study aimed to investigate the significance of the indocyanine green retention test at 15 min (ICG-R15) and the Albumin-Indocyanine Green Evaluation (ALICE) grading system in predicting severe posthepatectomy liver failure (PHLF) and postoperative mortality in HAE patients undergoing liver resection., Methods: A total of 105 HAE patients undergoing hepatectomy were enrolled in this study. The value of each variable in predicting severe PHLF was evaluated by univariate and multivariate logistic regression analyses. The area under the receiver operating characteristic (ROC) curves (AUC) were calculated to evaluate the predictive ability of the Child-Pugh grade, ICG-R15, and ALICE grading system. Also, patients were classified using the optimal cutoff value for ICG-R15 and different ALICE grades, and the incidence of severe PHLF and postoperative mortality were compared with the predicted values., Results: Out of the 105 HAE patients enrolled in this study, 34 patients (32.4%) developed severe PHLF. The ALICE grade and operative time were identified as independent predictors of severe PHLF. According to ROC analysis, the AUCs of the Child-Pugh grade, ICG-R15, and ALICE grade for predicting severe PHLF were 0.733 (95% confidence interval (CI), 0.637-0.814), 0.823 (95% CI, 0.737-0.891), 0.834 (95% CI, 0.749-0.900). The incidence of severe PHLF and postoperative 90-day mortality in patients with ICG-R15 > 7.2% were significantly higher than those with ICG-R15 ≤ 7.2% (P < 0.001; P = 0.008). Likewise, the incidence of severe PHLF and postoperative 90-day mortality in patients with ALICE grade 2 were higher than those with ALICE grade 1 within the Child-Pugh grade A (P < 0.001; P = 0.083)., Conclusion: ICG-R15 and ALICE grading system are powerful predictors of severe PHLF and postoperative mortality among HAE patients undergoing hepatectomy. Furthermore, a combination of the preoperative Child-Pugh grade and ALICE grading system may provide an even more precise and objective guidance and facilitate surgical decision-making for HAE patients., (© 2022. The Author(s).)

Background: The severity of metabolic dysfunction-associated fatty liver disease (MAFLD) reportedly plays a part in the etiology of colorectal tumors. However, there is no consensus., Methods: Studies relevant with the impact of MAFLD severity on the risk of colorectal neoplasms published before 24th April 2022 were screened. The pooled odds ratio (OR) with corresponding 95% confidence intervals (95% CI) was obtained using standard and cumulative meta-analyses. Subgroup, meta-regression, and sensitivity analyses were carried out to identify heterogeneity., Results: Fourteen studies with data from 37,824 MAFLD patients were included. The prevalence of colorectal neoplasms escalated with the progression of MAFLD compared to simple steatosis (OR = 1.93; 95% CI = 1.42-2.62). The magnitude and direction of the effect on these outcomes remained largely constant over time. Even after limiting the meta-analysis to 8 studies with available adjusted OR (aOR), the findings still suggested that MAFLD severity was positively related to colorectal neoplasms (aOR = 3.03; 95% CI = 2.02-4.53). Severe MAFLD was more likely to cause left colon tumors (OR = 3.86, 95% CI = 2.16-6.91) than right colon neoplasms (OR = 1.94, 95% CI = 1.15-3.28)., Conclusion: The severity of MAFLD was independently related to colorectal neoplasms and severe MAFLD was more likely to cause left colon tumors., (© 2022. The Author(s).)

Background: Vascular dementia (VAD) is the second most common type of dementia lacking effective treatments. Pentoxifylline (PTX), a nonselective phosphodiesterase inhibitor, displays protective effects in multiple cerebral diseases. In this study, we aimed to investigate the therapeutic effects and potential mechanisms of PTX in VAD., Methods: Bilateral common carotid artery stenosis (BCAS) mouse model was established to mimic VAD. Mouse behavior was tested by open field test, novel object recognition test, Y-maze and Morris water maze (MWM) tests. Histological staining, magnetic resonance imaging (MRI) and electron microscopy were used to define white matter integrity. The impact of PTX on microglia phagocytosis, peroxisome proliferator-activated receptors-γ (PPAR-γ) activation and Mer receptor tyrosine kinase (Mertk) expression was assessed by immunofluorescence, western blotting and flow cytometry with the application of microglia-specific Mertk knockout mice, Mertk inhibitor and PPAR-γ inhibitor., Results: Here, we found that PTX treatment alleviated cognitive impairment in novel object recognition test, Y-maze and Morris water maze tests. Furthermore, PTX alleviated white matter injury in corpus callosum (CC) and internal capsule (IC) areas as shown by histological staining and MRI analysis. PTX-treatment group presented thicker myelin sheath than vehicle group by electron microscopy. Mechanistically, PTX facilitated microglial phagocytosis of myelin debris by up-regulating the expression of Mertk in BCAS model and primary cultured microglia. Importantly, microglia-specific Mertk knockout blocked the therapeutic effects of PTX in BCAS model. Moreover, Mertk expression was regulated by the nuclear translocation of PPAR-γ. Through modulating PPAR-γ, PTX enhanced Mertk expression., Conclusions: Collectively, our results demonstrated that PTX showed therapeutic potentials in VAD and alleviated ischemic white matter injury via modulating Mertk-mediated myelin clearance in microglia., (© 2022. The Author(s).)

Background: Osteoporosis is a disease threatening the health of millions of individuals. Melatonin is found to be a potential anti-osteoporosis drug. However, whether melatonin plays a role against osteoporosis at different stages of the menopause and the underlying mechanisms are unknown., Methods: Ovariectomy was utilized as a model of perimenopausal and postmenopausal osteoporosis. A total of 100 mg/kg melatonin, or solvent alone, was added to the drinking water of the rats over 8 weeks. Perimenopausal rats immediately received intervention following ovariectomy while postmenopausal rats received intervention 8 weeks after ovariectomy. All rats underwent overdose anesthesia following intervention after which blood samples and femurs were collected for further analysis. Rat femurs were scanned using micro-CT and examined histologically. The serum levels of melatonin and osteogenic biochemical markers were measured and the expression of osteogenesis-associated genes (Runx2, Sp7) were quantified by real-time quantitative PCR. Alkaline phosphatase (ALP) activity and the gene expression (Col1a1, Runx2, Alpl, and Bglap) were measured after bone marrow mesenchymal stem cells (BMSCs) were osteogenically induced, both with and without melatonin in vitro. ALP staining and Alizarin Red S staining were used to identify osteogenesis., Results: Analysis by micro-CT and histological staining demonstrated that bone mass decreased and bone microarchitecture deteriorated over time after ovariectomy. Intervention with melatonin increased bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats. Serum levels of ALP continuously increased after ovariectomy while osteocalcin levels initially rose, then decreased. Melatonin increased the serum levels of ALP and osteocalcin and mRNA expression levels of Runx2 and Sp7 in normal and postmenopausal rats, the opposite of the markers in perimenopausal rats. In vitro study demonstrated that 100 μmol/L melatonin increased the mRNA expression of Col1a1, Runx2, and Alpl three and/or seven days after intervention, and Alpl and Bglap 14 d after intervention. Melatonin increased ALP activity and the extent of ALP and matrix mineralization in the late stage of osteogenesis., Conclusions: Bone mass continuously decreased after ovariectomy, while melatonin increased bone mass and ameliorated bone metabolism in normal, perimenopausal, and postmenopausal osteoporotic rats due to the induction of osteogenic differentiation in BMSCs., (© 2022. The Author(s).)

Background: Free circular RNAs(circRNAs) escaping from primary lesion of cancer to brain are strictly regulated by blood-brain barrier and therefore cerebrospinal fluid (CSF) circRNAs have potential advantage in exploring biomarkers and mechanism of brain metastasis in lung cancer., Methods: We collected paired cerebrospinal fluid, plasma and tumor tissues from 21 lung adenocarcinoma (ADC) patients with brain metastases (BM) and performed RNA sequencing., Results: Compared to tumor tissue and plasma, circRNAs in CSF were characterized by lower number of spieces but higher abundance. Notably, CSF-circRNAs displayed high heterogeneity among different BM lung ADC patients. A total of 60 CSF-circRNAs was identified and associated with shorten overall survival. The circRNA-miRNA-mRNA network analysis revealed that the 60 CSF-circRNAs involved in cancer-associated pathways, and five of them showed strong association with WNT signaling pathway. Validation by RT-PCR of CSF and in vitro experiments of the five candidate circRNAs support their potential roles in cell proliferation and invasion., Conclusions: In summary, our results depicted the heterogenous CSF-circRNAs profiles among BM lung ADC and implied that CSF-circRNAs may be promising prognosis-related biomarkers., (© 2022. The Author(s).)

Background: Long noncoding RNAs (lncRNAs) play a critical role in innate and adaptive immune responses. Thus, we aimed to identify ideal subtypes for head and neck squamous cell carcinoma (HNSCC) based on immune-related lncRNAs., Methods: TCGA HNSCC cohort was divided into two datasets (training and validation dataset), and 960 previously characterized immune-related lncRNAs were extracted for non-negative matrix factorization analysis. We characterized our HNSCC subtypes based on biological behaviors, immune landscape and response to immunotherapy in both training and validation cohort. A lncRNA-signature was generated to predict our HNSCC subtypes, and essential lncRNAs involved in tumor microenvironment (TME) were identified., Results: We developed and validated two HNSCC subtypes (C1 and C2) based on the 70 lncRNAs in the training and validation cohort. C2 subtype displayed good prognosis, high immune cell infiltration, immune-related genes expression and sensitivity to PD-1 blockade. C1 subtype was associated with high activity of mTORC1 signaling and glycolysis as well as high fraction of inactive immune cells. Finally, we generated a 31-lncRNA signature that could predict our above subtypes with high accurate. Additionally, TRG-AS1 was identified as the essential lncRNA involving TME formation. Knockdown of TRG-AS1 inhibited the expression of HLA-A, HLA-B, HLA-C, CXCL9, CXCL10 and CXCL11. High expression of TRG-AS1 indicated a favorable prognosis in HNSCC and anti-PD-L1 cohort (IMvigor210)., Conclusions: Our study establishes a novel HNSCC classification on the basis of 31-lncRNA, helping to identify beneficiaries for anti-PD-1 treatment. In addition, a critical lncRNA TRG-AS1 is identified as a new potential prognosis biomarker as well as therapeutic target., (© 2022. The Author(s).)

Neural tube defects (NTDs) remain one of the most life-threatening birth defects affecting infants. Most patients with NTDs eventually develop lifelong disability, which cause significant morbidity and mortality and seriously reduce the quality of life. Our previous study has found that ethionine inhibits cell viability by disrupting the balance between proliferation and apoptosis, and preventing neural stem cells from differentiating into neurons and astrocytes. However, how ethionine participates in the pathogenesis of neural tube development through N6-methyladenosine (m6A) modification remains unknown. This study aims to investigate METTL3- and ALKBH5-mediated m6A modification function and mechanism in NTDs. Herein, our results demonstrate that SAM play not only a compensatory role, it also leads to changes of m6A modification in neural tube development and regulation. Additionally, these data implicate that METTL3 is enriched in HT-22 cells, and METTL3 knockdown reduces cell proliferation and increases apoptosis through suppressing Wnt/β-catenin signaling pathway. Significantly, overexpression of ALKBH5 can only inhibit cell proliferation, but cannot promote cell apoptosis. This research reveals an important role of SAM in development of NTDs, providing a good theoretical basis for further research on NTDs. This finding represents a novel epigenetic mechanism underlying that the m6A modification has profound and lasting implications for neural tube development., (© 2021. The Author(s).)

Background: Fusobacterium nucleatum (F. n) is an important opportunistic pathogen causing oral and gastrointestinal disease. Faecalibacterium prausnitzii (F. p) is a next-generation probiotic and could serve as a biomarker of gut eubiosis/dysbiosis to some extent. Alterations in the human oral and gut microbiomes are associated with viral respiratory infection. The aim of this study was to characterise the oral and fecal bacterial biomarker (i.e., F. n and F. p) in COVID-19 patients by qPCR and investigate the pharyngeal microbiome of COVID-19 patients through metagenomic next-generation sequencing (mNGS)., Results: Pharyngeal F. n was significantly increased in COVID-19 patients, and it was higher in male than female patients. Increased abundance of pharyngeal F. n was associated with a higher risk of a positive SARS-CoV-2 test (adjusted OR = 1.32, 95% CI = 1.06 ~ 1.65, P < 0.05). A classifier to distinguish COVID-19 patients from the healthy controls based on the pharyngeal F. n was constructed and achieved an area under the curve (AUC) of 0.843 (95% CI = 0.688 ~ 0.940, P < 0.001). However, the level of fecal F. n and fecal F. p remained unaltered between groups. Besides, mNGS showed that the pharyngeal swabs of COVID-19 patients were dominated by opportunistic pathogens., Conclusions: Pharyngeal but not fecal F. n was significantly increased in COVID-19 patients, clinicians should pay careful attention to potential coinfection. Pharyngeal F. n may serve as a promising candidate indicator for COVID-19., (© 2021. The Author(s).)

Background: The current study investigated the performance of intravoxel incoherent motion diffusion (IVIM) technology in monitoring early renal injury in streptozotocin rats., Methods: Forty-eight Sprague-Dawley (SD) rats were divided into a control group and a diabetic mellitus (DM) group. Six rats in each group were randomly selected for MR scans at four different time points (0, 4, 8, and 12 weeks). The IVIM-derived parameters (D, D*, f and ADC values) of the renal cortex (CO), outer and inner stripe of the outer medulla (OS, IS), and internal medulla (IM) were acquired. Changes in each IVIM-derived parameter over time were analyzed, and differences between the two groups at each point were assessed. The associations between the IVIM parameters and IV collagen expression, urine volume (UV), blood urea nitrogen (BUN), and serum creatinine (Scr) were investigated., Results: The D and D* values of CO and the ADC values of CO, OS, IS and IM displayed significantly different trends between the two groups over time (P<0.05). In addition, significant correlations were discovered between the D* value of CO and UV and BUN (r=0.527, P=0.033; r=0.617, P=0.005), between the ADC value of IM and BUN (r=0.557, P=0.019) and between the f value of IM and BUN (r=0.527, P=0.033). No correlation was found between IVIM parameters and IV collagen expression and Scr., Conclusions: IVIM is a potential sensitive and noninvasive technology for the simultaneous assessment of early renal cortical and medullary injuries induced by diabetes., (© 2021. The Author(s).)

Objective: Although the significance of increased plasma D-dimer levels in activating coagulation and fibrinolysis has been reported, it is still controversial whether it can be used to predict the prognosis of lung cancer patients. This meta-analysis was performed to explore the beneficial role of plasma D-dimer as a prognostic factor in lung cancer patients according to a larger sample capacity., Materials and Methods: MEDLINE, EMBASE, and Cochrane Central databases were searched from inception to January 2021. The data are mainly hazard ratio(HR) with 95% confidence interval (CI) and Kaplan-Meier survival curves. The publication bias was examined by Egger's test., Results: Finally, a total of 28 studies, enrolling 8452 patients were included in the current meta-analysis. Our results showed that the OS (HR = 1.742, 95%CI:1.542-1.969, P < 0.001) and PFS (HR = 1.385, 95%CI:1.169-1.641, P = 0.003) in the high D-dimer group were significantly lower than those in the low D-dimer group. Subgroup analysis suggested that localization, detection methods and disease stage had an important effect on the prognosis., Conclusion: This meta-analysis revealed that the high plasma D-dimer level leads to lower survival than in the low D-dimer level, which might provide an important clue for high plasma D-dimer level as an independent factor of poor prognosis in patients with lung cancer., (© 2021. The Author(s).)

Background: Lung cancer is the most prevalent cancer, and the leading cause of cancer-related deaths in China. The aim of this study was to estimate the direct medical expenditure incurred for lung cancer care and analyze the trend therein for the period 2002-2011 using nationally representative data in China METHODS: This study was based on 10-year, multicenter retrospective expenditure data collected from hospital records, covering 15,437 lung cancer patients from 13 provinces diagnosed during the period 2002-2011. All expenditure data were adjusted to 2011 to eliminate the effects of inflation using China's annual consumer price index., Results: The direct medical expenditure for lung cancer care (in 2011) was 39,015 CNY (US$6,041) per case, with an annual growth rate of 7.55% from 2002 to 2011. Drug costs were the highest proportionally in the total medical expenditure (54.27%), followed by treatment expenditure (14.32%) and surgical expenditure (8.10%). Medical expenditures for the disease varied based on region, hospital level, type, and stage., Conclusion: The medical expenditure for lung cancer care is substantial in China. Drug costs and laboratory test are the main factors increasing medical costs., (© 2021. The Author(s).)

Background: The aim of our study was to identify the factors associated with unplanned reoperations among neonates who had undergone primary repair of gastrointestinal disorders., Methods: A retrospective chart review was conducted for neonates who underwent primary gastrointestinal surgery between July 2018 and September 2020. The neonates were divided into two cohort, depending on whether they had an unplanned reoperation. The primary outcome was the occurrence of unplanned reoperation. The risk factors that associated the occurrence of unplanned reoperation were examined., Main Results: Two hundred ninety-six neonates fulfilled the eligibility criteria. The incidence of unplanned reoperation was 9.8%. Analyses of all patients with respect of developing unplanned reoperation showed that the length of operative time was an independent risk factor [Odds Ratio 1.02; 95% confidence interval 1.00, 1.04; p = 0.03]. Patients with unplanned reoperation had a longer postoperative hospital length-of-stay [19.9 ± 14.7 vs. 44.1 ± 32.1 days; p<0.01]., Conclusion: The current study is the first analysis of risk factors associated with an unplanned reoperation in neonates undergoing primary repair of gastrointestinal disorders. The length of operative time is the only risk factor for an unplanned reoperation, and the unplanned reoperation can directly prolong the postoperative hospital length-of-stay., Trial Registration: This study was registered at http://www.chictr.org.cn/index.aspx with No. ChiCTR2000040260 .

Background: Xylo-oligosaccharide is the spotlight of functional sugar that improves the economic benefits of lignocellulose biorefinery. Acetic acid acidolysis technology provides a promising application for xylo-oligosaccharide commercial production, but it is restricted by the aliphatic (wax-like) compounds, which cover the outer and inner surfaces of plants., Results: We removed aliphatic compounds by extraction with two organic solvents. The benzene-ethanol extraction increased the yield of acidolyzed xylo-oligosaccharides of corncob, sugarcane bagasse, wheat straw, and poplar sawdust by 14.79, 21.05, 16.68, and 7.26% while ethanol extraction increased it by 11.88, 17.43, 1.26, and 13.64%, respectively., Conclusion: The single ethanol extraction was safer, more environmentally friendly, and more cost-effective than benzene-ethanol solvent. In short, organic solvent extraction provided a promising auxiliary method for the selective acidolysis of herbaceous xylan to xylo-oligosaccharides, while it had minimal impact on woody poplar.

Background: In the era of immunotherapy, it is still unclear which is the best first-line therapy for patients with oncogenic driver negative advanced non-squamous non-small cell lung cancer (NS-NSCLC) who cannot tolerate immunotherapy, or subsequent therapy for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy. To assess the optimal choice of first-line and maintenance treatment regimens, we performed a meta-analysis of prospective randomized controlled clinical trials (RCTs) of patients with NS-NSCLC on bevacizumab combined with chemotherapy., Methods: All eligible RCTs comparing pemetrexed-platinum with or without bevacizumab (PP ± B) and paclitaxel-carboplatin with bevacizumab (PC + B) as a first-line therapy, or comparing bevacizumab plus pemetrexed (Pem + B) and bevacizumab alone (B) as a maintenance treatment for advanced NS-NSCLC, were included after systematically searching web databases and meeting abstracts. The main research endpoints were comparisons of overall survival (OS) and progression-free survival (PFS). The other endpoints were objective response rate (ORR), 1-year PFS rate (PFSR1y) and major grade 3/4 treatment-related adverse events., Results: Data of 3139 patients from six RCTs were incorporated into analyses. Three RCTs were included in an analysis that compared PP ± B and PC + B as a first-line therapy for advanced NS-NSCLC. Patients treated with first-line PP ± B showed similar OS and ORR, but significantly improved PFS (hazard ratio [HR], 0.88) and PFSR1y (risk ratio [RR], 0.83), as compared to patients treated with PC + B (all P < 0.05). PP ± B resulted in higher rates of grade 3/4 anemia and thrombocytopenia, but lower rates of neutropenia, febrile neutropenia, and sensory neuropathy than PC + B (all P < 0.001). The other three RCTs were included in an analysis that compared Pem + B and B as a maintenance treatment. Compared with B, Pem + B maintenance treatment resulted in significant improvements in OS (HR, 0.88), PFS (HR, 0.64), and PFSR1y (RR, 0.70), but higher rates of anemia, thrombocytopenia, and neutropenia (all P < 0.001)., Conclusion: Although the first-line PP + B regimen had longer PFS and PFSR1y than the PC + B regimen, no OS difference was observed. Addition of pemetrexed to bevacizumab as maintenance therapy significantly improved OS compared with bevacizumab maintenance alone, but led to more toxicity.

Background: Wood basic density (WBD) is one of the most crucial wood property in tree and mainly determined the end use of wood for industry. However, the measurement WBD is time- and cost-consuming, which an alternatively fast and no-destructive measurement is needed. In this study, capability of NIR spectroscopy combined with partial least squares regression (PLSR) to quantify the WBD were examined in multiple wood species. To obtain more accurate and robust prediction models, the grain angle (0° (transverse surface), 45°, 90° (radial surface)) influence on the collection of solid wood spectra and a comparison of found variable selection methods for NIR spectral variables optimization were conducted, including significant Multivariate Correlation (sMC), Regularized elimination procedure (Rep), Iterative predictor weighting (Ipw) and Genetic algorithm (Ga). Models made by random calibration data selection were conducted 200 times performance evaluation., Results: These results indicate that 90° angle models display relatively highest efficiency than other angle models, mixed angle model yield a satisfied WBD prediction results as well and could reduce the influence of grain angle. Rep method shows a higher efficiency than other methods which could eliminate the uninformative variables and enhance the predictive performance of 90° angle and mix angle models., Conclusions: This study is potentially shown that the WBD (g/cm 3 ) on solid wood across grain angles and varies wood species could be measured in a rapid and efficient way using NIR technology. Combined with the PLSR model, our methodology could serve as a tool for wood properties breeding and silviculture study.