Search

Collaborative programming is being increasingly used to overcome the difficulties of the individual programming process. In this study, we investigated the effect of collaborative perception on cognitive engagement and learning outcomes in collaborative programming. We used a quasi-experimental research to determine the differences in cognitive engagement and learning outcomes of three groups with different levels of collaborative perception. The findings highlight several important conclusions. First, there were significant differences in cognitive engagement and learning outcomes across collaborative perception groups. Students with high levels of collaborative perception demonstrate more comprehensive and diverse cognitive engagement, resulting in higher learning outcomes compared to those with lower perception. Second, students in the low collaborative perception group had more Clarification-Elaboration cognitive connections, and students in the high collaborative perception group had stronger Clarification-Positioning and Clarification-Verification cognitive connections. Third, collaborative perception positively moderated the relationship between cognitive engagement and learning outcomes. In particular, three cognitive engagement, Clarification, Elaboration, and Positioning, had a greater impact on performance when moderated by collaborative perceptions. These findings have practical implications for educators and course designers, emphasizing the importance of considering students' collaborative perception when forming groups and promoting effective collaborative programming.

Zn2P2O7, a representative material in the A2P2O7 family, exhibits negative thermal expansion (NTE) and possesses a remarkable negative linear expansion coefficient. Here we employ variable temperature and high-pressure Raman spectroscopy to investigate the phonon anomalies arising from the α- to β-phase transition in Zn2P2O7. Combing with the refinement results of our X-ray diffraction (XRD) experiment, we have identified the specific variations of the bond lengths, bond angles and the polyhedral distortion indexes that result in the phonon anomalies. Some certain phonons, whose energy decreases with increasing pressure, have been demonstrated to give rise to negative Grüneisen parameters that can characterize phonon anharmonicity and lead to lower thermal expansion in the α-phase of Zn2P2O7 compared to the β-phase. These results provide new insight into the relationship between lattice deformation and phonon anomalies during the structural phase transition in the NTE material Zn2P2O7.

Summary: Background: It remains unknown how ambient temperature impact pneumonia of various infectious causes. Methods: Based on the national death registry covering all counties in Chinese mainland, we conducted an individual-level case-crossover study in China from 2013 to 2019. Exposures were assigned at residential addresses for each decedent. Conditional logistic regression model combined with distributed lag non-linear models were used to estimate the exposure-response associations. The attributable fractions due to non-optimum temperature were calculated after accounting for spatial and temporal patterns for the excess risks. Findings: The exposure-response curves were inversely J-shaped with both low and high temperature increasing the risks, and the effect of low temperature was stronger. Extremely low temperature was associated with higher magnitude of influenza-related pneumonia [relative risk (RR): 2.46, 95% confidence interval (CI): 1.62–3.74], than viral pneumonia (RR: 1.89, 95% CI: 1.55–2.30) and bacterial pneumonia (RR: 1.81, 95% CI: 1.56–2.09). The magnitudes of RRs associated with extremely high temperature were similar among the three categories of pneumonia. The mortality attributable fraction for influenza-related pneumonia (29.78%) was the highest. The effects were stronger in people of low education level or residence in the north. Interpretation: This nationwide study presents findings on the varied risk and burden of pneumonia mortality of various infectious causes, and highlights the susceptibility of influenza-related pneumonia to ambient low temperature. Funding: This study is supported by the National Key Research and Development Program (2022YFC3702701), the Shanghai Municipal Science and Technology Commission (21TQ015) and Shanghai International Science and Technology Partnership Project (21230780200).

Background: Future warming is projected to increase the heat-related mortality burden, especially for vulnerable populations. However, most previous studies focused on non-accidental morbidity or mortality, with far less research on heat-related accidental events. Methods: We collected individual accidental death records among all residents in Chinese mainland from June to August during 2013–2019. Accidental deaths were further divided into several subtypes by different causes. We used an individual-level, time-stratified, case-crossover study design to estimate the association between daily mean temperature and accidental deaths, and estimate its variation in seven geo-climatic zones, age (5–64, 65–74, ≥75), and sex (male, female). We then estimated the temperature-related excess accidental deaths under global warming scenarios of 1.5, 2, and 3℃. Findings: A total of 711,929 accidental death records were included in our study. We found that higher temperatures were associated with increased risks of deaths from the total accidental events and four main subtypes, including traffic, falls, drowning, and unintentional injuries. We also found that younger individuals (ages 5–64) and males faced a higher risk of heat-related mortality due to total accidents, traffic incidents, and drowning. For future climate scenarios, even under the 1.5℃ climate change scenario, 6,939 (95% eCI (empirical Confidence Interval): 6,818–7,067) excess accidental deaths per year are attributed to higher summertime daily temperature over mainland China, and the number of accidental deaths would increase by 16.71% and 33.59% under the 2℃ and 3℃ climate change scenarios, respectively. For residents living in southern coastal and northwest inland regions, the projected increase in accidental death is higher. Conclusions: This nationwide study confirms that higher summer temperatures are linked to an increased risk of accidental deaths. Younger age groups and males face a higher risk. This indicates that current estimates of the health effects of climate change might be underestimated, particularly for younger populations.

In this work, a metasurface consisting of disk-ring Si nanostructures on a SiO2 substrate is proposed and numerically simulated. The Si disk-ring structure can excite and manipulate anapole state, and periodic array supports lattice resonance simultaneously, which can improve the near-field enhancement in the gap region. The maximum E-field enhancement can be up to 346 times, and a transmission dip with an ultra-narrow bandwidth of 0.34 nm and a Q-factor of 4460 is shown. When the central disk has an offset, the near-field enhancement can be affected. In the case of y-direction offset, the maximum E-field enhancement can be up to 468 times. The near field energy is concentrated in the gap region, easy to interact with probing molecule in surrounding environment. Meanwhile, the designed metasurface shows a sensing performance of 387 nm/RIU. The strong energy confinement and high Q-factor of the proposed structure give an opportunity to enhance the interaction between light and matter, which may have potential applications in nonlinear optics, optical sensors and surface enhanced Raman scattering.

PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp (RGDRGD) 30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus. The active endostatin fragment of PEP06 directly targets tumor cells and exerts an antitumoral effect. However, little is known about the kinetics and degradation products of PEP06 in vitro or in vivo. In this study, we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species; we further identified the degradation characteristics of its cleavage products. PEP06 underwent rapid enzymatic degradation in multiple types of living cells, and the liver, kidney, and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06. We identified metabolites of PEP06 using full-scan mass spectrometry (MS) and tandem MS (MS2), wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide, formed by successive losses of amino acids. The metabolites were C and N terminal truncated products of PEP06. The structures of 11 metabolites (M6, M7, M16, M17, M21, M25, M33, M34, M39, M40, and M42) were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites. We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06, which can support further drug research.

Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that contains two catalytic domains and a zinc-finger ubiquitin binding domain (ZnF-UBP) domain. The deacetylation function of HDAC6 has been extensively studied with common substrates such as α-tubulin, cortactin, and Hsp90. Apart from its deacetylase activity, HDAC6 ZnF-UBP binds to unanchored ubiquitin of specific sequences and serves as a carrier for transporting aggregated proteins. As a result, aggresomes are formed and protein degradation is facilitated by the autophagy-lysosome pathway. This HDAC6-dependent microtubule transport can be used by cells to assemble and activate inflammasomes, which play a critical role in immune regulation. Even viruses can benefit from the carrier of HDAC6 to assist in uncoating their surfaces during their infection cycle. However, HDAC6 is also capable of blocking virus invasion and replication in a non-enzymatic manner. Given these non-enzymatic functions, HDAC6 is closely associated with various diseases, including neurodegeneration, inflammasome-associated diseases, cancer, and viral infections. Small molecule inhibitors targeting the ubiquitin binding pocket of HDAC6 have been investigated. In this review, we focus on mechanisms in non-enzymatic functions of HDAC6 and discuss the rationality and prospects of therapeutic strategies by intervening the activation of HDAC6 ZnF-UBP in concrete diseases.

N6-Methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA, playing critical role in various bioprocesses. Like other epigenetic modifications, m6A modification can be catalyzed by the methyltransferase complex and erased dynamically to maintain cells homeostasis. Up to now, only two m6A demethylases have been reported, fat mass and obesity-associated protein (FTO) and alkylation protein AlkB homolog 5 (ALKBH5), involving in a wide range of mRNA biological progress, including mRNA shearing, export, metabolism and stability. Furthermore, they participate in many significantly biological signaling pathway, and contribute to the progress and development of cancer along with other diseases. In this review, we focus on the studies about structure, inhibitors development and biological function of FTO and ALKBH5.

Permission delegation has become a new way for data sharing by delegating the authorized permission to other users. A flexible authorization model with strict access control policies is promising for electronic health record (EHR) sharing with security. In this paper, a blockchain-based multi-hop permission delegation scheme with controllable delegation depth for EHR sharing has been presented. We use the interplanetary file system (IPFS) for storing the original EHRs. Smart contracts and proxy re-encryption technology are implemented for permission delegation. In order to ensure data security, we use attribute-based encryption to provide fine-grained access control. Additionally, blockchain is used to achieve traceability and immutability. We deploy smart contracts so that the delegation depth can be set by delegators. Security analysis of the proposed protocol shows that our solution meets the designed goals. Finally, we evaluate the proposed algorithm and implement the scheme on the Ethereum test chain. Our scheme outperforms the competition in terms of performance, according to the results of our experiments.

Summary: Background: The non-causal and causal associations, possible age and sex differences between living alone and all-cause mortality among adults were unclear. We aimed to assess the association and causal relation between living alone and all-cause mortality among community-dwelling adults, addressing the certainty of evidence, possible age and sex differences. Methods: We searched Medline, Embase, and APA PsycINFO for cohort studies examining the association between living alone and all-cause mortality on November 19, 2021. We used the GRADE approach to assess certainty of evidence, and the Instrument for the Credibility of Effect Modification Analyses (ICEMAN) to evaluate credibility of subgroup inferences and conducted a meta-analysis of measures of association between living alone and mortality. The study was registered with PROSPERO, CRD42021290895. Findings: 18 cohort studies with 62,174 adults proved eligible. Living alone was associated with mortality (relative risk (RR) = 1.15, 95% confidence interval (CI) 1.08–1.23). Both age and sex modified the association (high and moderate credibility, separately). Living alone increased the risk of dying only in younger but not older individuals (ratio of RRs = 1.59, interaction P = 0.003; younger RR 1.41, 95% CI 1.17–1.71, high certainty for prognosis, low for causation; older RR = 1.05, 95% CI 0.91–1.22, moderate certainty for prognosis, very low for causation). Living alone increased risk to a greater extent in males than females (ratio of RRs = 1.39, 95% CI 1.14–1.70; interaction P = 0.001, males RR = 1.41, 95% CI 1.17–1.71, high certainty for prognosis, low for causation; females RR = 1.15, 95% CI 0.99–1.33; moderate for prognosis factor, very low for causation). Interpretation: Living alone is associated with increased mortality in individuals under 65 years (high certainty) but not with those over 75 years; the association may be causal (low certainty). Associations, and possibly effects, may be stronger in men than women. Funding: None.

Scoparone (SCO) has a wide range of pharmacological activities, especially antioxidant and lipid-lowering ones. The purpose of this study was to investigate the effect of SCO on alleviating liver injury induced by alcohol and high-fat diet (HFD) in mice. The pathomorphology, biochemical indices, lipid accumulation, alcohol metabolism, oxidative stress and inflammatory response were examined. RNA sequencing analysis was performed on liver tissues to identify differentially expressed genes (DEGs) and signaling pathways, thus elucidating the mechanism of SCO in protecting the liver. Finally, some of the DEGs were validated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. The results showed that SCO had significant hepatoprotective effects, which could inhibit lipid accumulation, improve alcohol metabolism, reduce oxidative stress and inhibit inflammatory response. RNA sequencing results showed that 1208 genes were differentially expressed in liver tissues of mice treated with alcohol and HFD, while 2143 genes were significantly changed after SCO intervention. These DEGs were mainly involved in metabolism of xenobiotics by cytochrome P450, fatty acid (triglyceride) metabolism, and cholesterol synthesis pathways. In addition, the results of qRT-PCR and Western blot were consistent with the RNA sequencing. SCO can alleviate liver injury induced by alcohol and HFD in mice, and its mechanism may be related to regulating alcohol metabolism and lipid metabolism pathways.

Background: Non-optimum ambient temperature has not been widely perceived as an important environmental risk factor for asthma, and the association between ambient temperature and pulmonary function is rarely explored. Our study aimed to investigate the associations between non-optimum ambient temperature and pulmonary function among asthmatic adult patients. Methods: We performed a longitudinal study among 4,992 eligible adult asthmatic patients in 25 cities of China from 2017 to 2020. The patients were required to complete pulmonary function test every day in the morning and evening. Linear mixed-effects models and distributed lag non-linear models were used to evaluate the associations between ambient temperature and pulmonary function. Results: We evaluated 298,396 records of pulmonary function tests. We found inversely J-shaped exposure–response relationship curves for ambient temperature and pulmonary function. The effects of extreme low temperature occurred at lag 0 h and vanished at lag 72 h (almost 3 days). Compared with referent temperature (29.5 °C), extreme low temperature (−9.4 °C) was associated with decreases of 60.4 mL in FEV1, 299.7 mL/s in PEF, and 101.5 mL in FVC. Extreme high temperature (34.2 °C) was associated with decreases of 26.0 mL in FEV1, 35.8 mL/s in PEF, and 23.4 mL in FVC. Patients of male, overweight, and elder ages were vulnerable populations, and cold effects were more prominent in the south and in areas without central heating. Conclusions: Both extreme low and high ambient temperatures were associated with decreased pulmonary function in adult asthmatic patients. The effect could last for almost 3 days and low temperature was more harmful.

Aims: Although previous studies have linked short-term exposure to fine particulate matter (PM2.5) air pollution with various molecular biomarkers of cardiovascular system, limited evidence is available for indicators at clinical or subclinical levels. We examined the associations between short-term PM2.5 exposure and a range of clinical or subclinical indicators of cardiovascular health in general population. Methods and results: A longitudinal repeated-measure study was conducted among 247,640 participants who repeatedly visited health examination centers in 15 typical cities across China from 2013 to 2020. A total of 19 well-established indicators of cardiovascular risk or injury were evaluated and air quality data at nearest fixed-site monitors were collected. Linear mixed-effects models with distributed lag models were used to analyze the potentially lagged effects of PM2.5. The average daily PM2.5 concentration was 48 μg/m3 during the study period. PM2.5 exposure was associated with significant changes of 16 indicators with the effects generally peaked on lag 0 to 3 day. For an interquartile range (IQR) elevation (37 μg/m3) in PM2.5 concentrations over lag 0–7 day, the cumulative percentage changes were 0.50% to 1.27% in heart rates and blood pressure, 0.10% to 5.04% in inflammatory markers, −0.29% to 1.39% in blood viscosity parameters, −0.67% to 3.45% in blood lipids, 0.89% in blood homocysteine, 0.13% to 0.78% in myocardial enzymes, and 3.03% in pulse wave velocity. These associations were not substantially changed after adjusting concomitant exposures to gaseous pollutants. Conclusion: Short-term exposure to PM2.5 may induce early cardiovascular effects in general population, including acute inflammation, myocardial injury, increased blood viscosity, vascular stiffness and hyperlipidemia.

Background: Core outcome sets (COSs) are the minimum outcomes which should be measured and reported by researchers investigating a specific condition. The definition of standards of COSs vary across different health-related areas. This investigated the characteristics of COSs regarding obstetrics and gynecology (OG) and examined the reports and designs of standards of OG COSs. Methods: A comprehensive search was conduced on the COMET database on December 20, 2019 to identify systematic reviews on COSs. Two reviewers independently evaluated whether the reported OG COS met the reporting requirements as stipulated in the Core Outcome Set-STAndards for Reporting (COS-STAR) statement checklist and the minimum design recommendations as outlined in the Core Outcome Set-STAndards for Development (COS-STAD) checklist. Results: Forty-four OG COSs related to 26 topics were identified. None of them met all the 25 standards of COS-STAR statement which representing 18 items considered essential for transparent and complete reporting list for all COS studies (range: 6.0-24.0, median: 14.0). The compliance rates to 16 standards of methods and result sections ranged from 27.3%–68.2%. Total COS-STAR compliance items for OG COSs with the prior protocol was significantly higher than without prior protocol (MD = 3.846, 95% CI: 0.835–6.858, P = 0.012). None of the OG COSs met all the 12 criteria in the COS-STAD minimum standards (range: 3.0-11.0, median: 5.0). The compliance rates for all three standards of stakeholders involved and all four standards of the consensus process were lower than 60%. Conclusions: Methodological and reporting standards of OG COSs should be improved.

The short-term associations of fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) with pulmonary function were inconsistent and rarely evaluated by dynamic measurements. Our study aimed to investigate the associations of PM2.5 and PM2.5–10 with real-time pulmonary function. We conducted a longitudinal study based on dynamic pulmonary function measurements among adult asthmatic patients in 25 cities of 19 provincial regions of China from 2017 to 2020. Linear mixed-effects models combined with polynomial distributed lag models were used for statistical analysis. A total of 298,396 records among 4,992 asthmatic patients were evaluated. We found generally inverse associations of PM2.5 and PM2.5–10 with 16 pulmonary function indicators that were independent of gaseous pollutants. The associations occurred at lag 1 d, became the strongest at lag 4 d, and vanished a week later. PM2.5-10 had stronger associations than PM2.5, especially in southern China. Nationally, an interquartile increase in PM2.5-10 (28.0 μg/m3) was significantly associated with decreases in forced expiratory volume in 1 s (FEV1, 41.6 mL), the ratio of FEV1 in forced vital capacity (1.1%), peak expiratory flow (136.9 mL/s), and forced expiratory flow at 25–75% of forced vital capacity (54.3 mL/s). We observed stronger associations in patients of male, BMI ≥ 25 kg/m2, age ≥ 45 years old, and during warm seasons. In conclusion, this study provided robust evidence for impaired pulmonary function by short-term exposure to PM2.5 and PM2.5-10 in asthmatic patients using the largest dataset of dynamic monitoring. The associations can last for one week and PM2.5-10 may be more hazardous.

Epidemiological evidence from ambulatory blood pressure monitoring is needed to clarify the associations of particulate air pollution with blood pressure and potential lag patterns. We examined the associations of fine and coarse particulate matter (PM2.5, PM2.5–10) with ambulatory blood pressure among 7108 non-hypertensive participants from 7 Chinese cities between April 2016 and November 2020. Hourly concentrations of PM2.5 and PM2.5–10 were obtained from the nearest monitoring stations. We measured four blood pressure indicators, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP). Linear mixed-effect models combined with distributed lag models were applied to analyze the data. Generally, very short-term exposure to PM2.5 was significantly associated with elevated blood pressure. These effects occurred on the same hour of blood pressure measurement, attenuated gradually, and became insignificant approximately at lag 12 h. An interquartile range (IQR, 33 μg/m3) increase of PM2.5 was significantly associated with cumulative increments of 0.58 mmHg for SBP, 0.31 mmHg for DBP, 0.38 mmHg for MAP, and 0.33 mmHg for PP over lag 0 to 12 h. The exposure–response relationship curves were almost linear without thresholds, but tended to be flat at very high concentrations. No significant associations were observed for PM2.5–10. Our study provides independent and robust associations between transient PM2.5 exposure and elevated blood pressure within the first 12 h, and reinforces the evidence for a linear and non-threshold exposure–response relationship, which may have implications for blood pressure management and hypertension prevention in susceptible population.

Objective: To gain a deeper understanding of the hot topics and future prospects of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors treatment of cancer through scientometric analysis of the top-100 most cited clinical trials. Materials and methods: We searched the Web of Science Core Collection database from 1980 to June 2019. Two reviewers independently screened the top-100 most cited clinical trials that defined by the National Institutes of Health starting from the most cited article. Title, year of publication, citations, type of cancer, and focused aspects of outcomes were extracted from included clinical trials. VOSviewer software (version 1.6.9) and Excel 2016 were used to do statistical analysis. The evidence mapping was used to present the relationship between cancers, drugs, citations, and outcomes, etc. Results: The top-100 most cited clinical trials published from 2010 to 2018 in nine journals with high impact factor (IF) (IF2018:6.68–70.67), and Lancet Oncology (USA) published the most clinical trials (n = 29, IF2018 = 35.3856). The total number of citations of the top-100 most cited clinical trials was from 59 to 5606. 920 authors from 34 countries and 458 organizations participated in publishing the top-100 most cited clinical trials. The USA (n = 95) and Memorial Sloan-Kettering Cancer Center (n = 31) contributed the most publications. Based on the evidence mapping, there are 25 different types of cancers (e.g. lung cancer, melanoma, and renal cell cancer) and five focused aspects of outcomes (e.g. safety and efficacy). Conclusion: The USA was the dominant country. Anti-PD-1/PD-L1 drugs were widely used to treat lung cancer, melanoma, renal cell cancer, and Hodgkin lymphoma. More exploration should be done to explore the use of anti-PD-1/PD-L1 drugs to treat more type of cancers in future research.

Heavy metal(loid) contamination represents an immense challenge in sustainable agriculture. Arsenic, in particular, poses a great risk to the quality of agricultural products (e.g., rice grain). The sulfur amendment is recommended as an effective practice to remediate heavy metal(loid)–polluted soil, given its function in enhancing crop production and alleviating heavy metal(loid) accumulation in the plant. This study aims to investigate the roles of sulfur fertilizer on arsenic accumulation in rice and to explore the key mechanisms. In this study, Elemental sulfur (ES) and gypsum sulfur (GS) were chosen as sulfur fertilizers, with different application rates (0, 0.15, and 0.30 g S kg−1 soil). The results showed that ES and GS treatment significantly increased rice grain yield by 46.6–59.7% and significantly reduced the rice grain arsenic content by more than 39.1%. The sulfur treatment decreased soil pe + pH values. ES treatment increased the availability of arsenic in the bulk soil, whereas GS showed little effect. Sulfur application promoted the formation of iron and manganese plaques, which could suppress the migration of arsenic from soil to rice root. In addition, the sulfur treatment decreased the arsenic that migrating from rice roots to grains by 33.3–66.7%. This study indicates that sulfur application could increase arsenic availability in paddy soil; however, it can inhibit arsenic accumulation in rice grains via increasing the root plaques content and inhibiting the translocation of arsenic from roots to grains.

Background: Upper respiratory infections (URIs) are among the most common diseases. However, the related burden has not been comprehensively evaluated. Thus, we designed the present study to describe the global and regional burden of URIs from 1990 to 2019. Methods: A secondary analysis was performed on the incidence, mortality, and disability-adjusted life years (DALYs) of URIs in different sex and age groups, from 21 geographic regions, 204 countries and territories, between 1990 and 2019, using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Countries and territories were categorized according to Socio-demographic Index (SDI) quintiles. Findings: Globally, the incident cases of URIs reached 17·2 (95% uncertainty interval: 15·4 to 19·3) billion in 2019, which accounted for 42·83% (40·01% to 45·77%) cases from all causes in the GBD 2019 study. The age-standardized incidence rate remained stable from 1990 to 2019, while significant decreases were found in the mortality and DALY rate. The highest age-standardized incidence rates from 1990 to 2019 and the highest age-standardized DALY rates after 2011 were observed in high SDI regions. Among all the age groups, children under five years old suffered from the highest incidence and DALY rates, both of which were decreased with increasing age. Fatal consequences of URIs occurred mostly in the elderly and children under five years old. Interpretation: The present study provided comprehensive estimates of URIs burden for the first time. Our findings, highlighting the substantial incidence and considerable DALYs due to URIs, are expected to attract more attention to URIs and provide future explorations in the prevention and treatment with epidemiological evidence. Funding: The study was funded by the National Natural Science Foundation of China (81770057).

Nano-hydroxyapatite (HA-NPs) coating on the surface of titanium is an effective way to improve the osteoinductivity of implants. However, particle agglomeration and uncontrollable structure of HA-NPs results in limited osteogenic capability. In this study, pulse electrochemical deposition method was used to drive PPy in situ, and HA-NPs as well as the osteoinductive drug Dex were introduced to PPy based on its doping characteristics to endow the titanium-based composite coating with long-term osteoinductivity during the osseointegration process. During the oxidative polymerization of PPy, PO43− and Dex− were doped into the main chain of PPy, and HA was formed due to the electrostatic interaction of PO43− and Ca2+, finally realizing the co-deposition of HA-NPs and Dex. Dex drug release experiments showed that the doping effect of PPy has reduced the release rate of Ca2+ from the coating and increased the physiological stability of the coating. The in vitro evaluation of osteoblasts and vascular endothelial cells showed that the number of cells increased steadily with good proliferation conditions, showing promising osteogenic ability and angiogenic property. In summary, a bioactive PPy@HA/Dex nanocomposite coating with sustained osteoinductivity was successfully constructed on the titanium surface using pulse electrochemical method.

Background: Lianhuaqingwen (LH) has been proven effective for influenza. However, the promotion of LH for the treatment of patients with COVID-19 remains controversial. Therefore, our study aimed to assess the efficacy and safety of Lianhuaqingwen (LH) in treating patients with COVID-19 by a systematic review and meta-analysis. Methods: We conducted the literature search using six electronic databases from December 1, 2019, to June 2, 2020. Cochrane Risk of Bias tool was used to assess the quality of randomized controlled trials. Newcastle-Ottawa Scale was used to assess the quality of case control studies. Agency for Healthcare Research and Quality checklist was used to assess the quality of case series. All analyses were conducted by RevMan 5.3. For outcomes that could not be meta-analyzed were performed a descriptive analysis. Results: Eight studies with 924 patients were included. Three studies were RCTs, three were case control studies, and two were case series. The quality of the included studies was poor. Compared with patients treated by conventional treatment, patients treated by LH combined with conventional treatment have a higher overall effective rate (RR = 1.16, 95%CIs: 1.04∼1.30, P = 0.01) and CT recovery rate (RR=1.21, 95%CIs: 1.02∼1.43, P = 0.03). Patients of LH groups have a lower incidence of diarrhea (5.6% vs.13.4%), and have statistically significant (P = 0.026). But the rate of abnormal liver function in the combined medication group is higher than that in the single LH group. Conclusion: LH combined with conventional treatment seems to be more effective for patients with mild or ordinary COVID-19.

Objective: Using the traditional Chinese medicine theory of “Bi-zheng'' caused by kidney deficiency, combined with modern medical science and technology, this study assessed the relationships among organ weight, cytokines, pathological manifestations, and traditional Chinese medicine kidney deficiency syndrome in rats with rheumatoid arthritis. Methods: Sixty Sprague–Dawley rats were randomly divided into normal, collagen-induced arthritis (CIA) model, and kidney deficiency arthralgia model groups. Rats in the kidney deficiency arthritis group underwent removal of the testis or ovary and administration of an inflammatory agent. Rats in the control group solely received an inflammatory agent. Type II collagen-induced arthritis was induced within 1 week of the winter solstice or summer solstice, in order to sample organs and observe the mental state, posture, fur color, activity level, excrement, body weight, and organ weight of the rats. Results: Compared with the normal and CIA model groups, the kidney deficiency arthralgia model group showed fast and acute onset, prominent symptoms, most obvious potential joint swelling, worst general state, and least amount of weight gain. Compared with the normal group, the proportion of thymus, spleen, and adrenal glands of model rats were larger in winter, with varying degrees of hyperplasia and hypertrophy; these differences were statistically significant (P

The purpose of this study is to use Dicliptera chinensis (L.) Juss (Acanthaceae) polysaccharide (DCP) to act on the NF-κB inflammatory pathway and Fas/FasL ligand system, in order to find a new method to improve immune liver injury. Lipopolysaccharide (LPS) was used to establish an injury model in vivo (Kunming mice) and in vitro (LO2 cells). In this experiment, hematoxylin-eosin (H&E) staining and related biochemical indicators were used to observe the pathological changes of liver tissues, oxidative stress and inflammatory reactions. Immunohistochemistry, ELISA, RT-PCR and Western blot were used to detect protein or mRNA expressions associated with inflammation response and apoptosis. The experimental results show that the model group has obvious liver cell damage and inflammatory infiltration. After DCP intervention, it could significantly reduce the levels of ALT, AST, ALP, TBIL and MDA in serum, and increase the content of SOD and GSH-Px. In addition, DCP can reduce the expression level of NF-κB in the liver and reduce the release of downstream inflammatory factors TNF-α, IL-6 and IL-1β, thereby reducing the inflammation. At the same time, DCP can significantly inhibit the expression of Fas/FasL ligand system and apoptosis related-proteins and mRNA, which in turn can reduce cell apoptosis. In conclusion, DCP can alleviate liver injury by inhibiting liver inflammation and apoptosis, which provides a new strategy for clinical treatment of immune liver injury.

Background: It remains unclear which size of particles has the strongest effects on heart rate variability (HRV). Objective: To explore the association between HRV parameters and daily variations of size-fractionated particle number concentrations (PNCs). Methods: We conducted a longitudinal repeated-measure study among 78 participants with a 24-h continuous ambulatory Holter electrocardiographic recorder in Shanghai, China, from January 2015 to June 2019. Linear mixed-effects models were employed to evaluate the changes of HRV parameters associated with PNCs of 7 size ranges from 0.01 to 10 μm after controlling for environmental and individual confounders. Results: On the concurrent day, decreased HRV parameters were associated with increased PNCs of 0.01–0.3 μm, and smaller particles showed greater effects. For an interquartile range increase in ultrafine particles (UFP, those

Background: The coronavirus disease 2019 (COVID-19) has caused a worldwide pandemic, and traditional Chinese medicine (TCM) has played an important role in response. We aimed to analyze the published literature on TCM for COVID-19, and provide reference for later research. Methods: This study searched the CBM, CNKI, PubMed, and EMBASE from its establishment to March 11, 2020. VOSviewer 1.6.11 and gCLUTO 2.0 software were used to visually analyze the included studies. Results: A total of 309 studies were included, including 61 journals, 1441 authors, 277 institutions, and 27 provinces. Research collaborations among regions were among those close in geographical distance. The collaborations of institutions and authors were more likely to be restricted to the same region. Among the authors with frequency greater than two (65 authors), only 19 authors had connection with others. More than 70% (358/491) of keywords were only presented once, and 20 keywords were shown more than 10 times. Five research topics were identified: Data mining method based analysis on the medication law of Chinese medicine in prevention and management of COVID-19; exploration of active compounds of Chinese medicine for COVID-19 treatment based on network pharmacology and molecular docking; expert consensus and interpretation of COVID-19 treatment; research on the etiology and pathogenesis of COVID-19; and clinical research of TCM for COVID-19 treatment. Conclusion: The research hotspots were scattered, and the collaboration between authors and institutions needed to be further strengthened. To improve the quality and efficiency of research output, the integration of scientific research and resources, as well as scientific collaboration are needed.

Background: Clinical responses to EGFR tyrosine kinase inhibitors (TKIs) are restricted to tumors harboring specific activating mutations and even then, not all tyrosine kinase inhibitors provide clinical benefit. All TKIs however, effectively inhibit EGFR phosphorylation regardless of the mutation present. Methods: High-throughput, high-content imaging analysis, western blot, Reversed phase protein arrays, mass spectrometry and RT-qPCR. Findings: We show that the addition of TKIs results in a strong and rapid intracellular accumulation of EGFR. This accumulation mimicked clinical efficacy as it was observed only in the context of the combination of a TKI-sensitive mutation with a clinically effective (type I) TKI. Intracellular accumulation of EGFR was able to predict response to gefitinib in a panel of cell-lines with different EGFR mutations. Our assay also predicted clinical benefit to EGFR TKIs on a cohort of pulmonary adenocarcinoma patients (hazard ratio 0.21, P=0.0004 [Cox proportional hazard model]) and could predict the clinical response in patients harboring rare mutations with unknown TKI-sensitivity. All investigated TKIs, regardless of clinical efficacy, inhibited EGFR phosphorylation and downstream pathway activation, irrespective of the mutation present. Intracellular accumulation of EGFR depended on a continued presence of TKI indicating (type I) TKIs remain associated with the protein even after its dephosphorylation. Accumulation therefore is likely caused by two consecutive conformational changes, induced by both activating mutation and TKI, that combined block EGFR-membrane recycling. Interpretation: We report on an assay that mimics the discrepancy between molecular and clinical activity of EGFR-TKIs, which may allow response prediction in vitro and helps understand the mechanism of effective inhibitors.

Reactive oxygen species (ROS) are key regulators in cell proliferation, survival, tumor initiation and development. However, the role of ROS in tumor metastasis is less clear. Here, we show that oxidative stress inhibited tumor metastasis via activation of Hippo kinase MST1/2, which led to the phosphorylation and nuclear accumulation of FoxO3a, resulting in upregulation of ΔNp63α expression and suppression of cell migration independent of YAP. Strikingly, while loss of MST1 led to and disruption of cell-cell junction exemplified by reduced E-cadherin expression, resulting in scattered cell growth, loss of MST2 led to disruption of cell-matrix adhesion as evidenced by reduced integrin β4, resulting in increased cell migration and tumor metastasis. Furthermore, expression of MST1 and MST2 was down-regulated in human breast carcinoma. Furthermore, oxidative stress inhibited HER2-or PI3K-mediated tumor metastasis via the MST2-FoxO3a-ΔNp63α pathway. Together, these results that this noncanonical Hippo MST2-FoxO3a-ΔNp63α pathway may play a critical role in ROS-mediated regulation of cell migration and tumor metastasis. Keywords: Hippo kinase, Metastasis, ΔNp63α, Cell-cell junction, Cell-matrix adhesion

The rate-limiting enzyme in the mevalonic acid (MVA) pathway which can lead to triterpenoid saponin glycyrrhizic acid (GA) is 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR). In order to reveal the effect of copy number variation in the HMGR gene on the MVA pathway, the HMGR gene from Glycyrrhiza uralensis Fisch. (GuHMGR) was cloned and over-expressed in Pichia pastoris GS115. Six recombinant P. pastoris strains containing different copy numbers of the GuHMGR gene were obtained and the content of ergosterol was analyzed by HPLC. The results showed that all the recombinant P. pastoris strains contained more ergosterol than the negative control and the strains with 8 and 44 copies contained significantly more ergosterol than the other strains. However, as the copy number increased, the content of ergosterol showed an increasing–decreasing–increasing pattern. This study provides a rationale for increasing the content of GA through over-expressing the GuHMGR gene in cultivars of G. uralensis.

Triclosan (TCS), a biocide used in various day-to-day products, has been associated with several toxic effects in aquatic organisms. In the present study, biochemical and hematological alterations were evaluated after 14 d (sublethal) exposure of tap water (control), acetone (solvent control), 5, 10, 20, and 50 μg/L (environmentally relevant concentrations) TCS to the embryos/hatchlings of Cirrhinus mrigala, a major freshwater carp distributed in tropic and sub-tropical areas of Asia. A concentration-dependent increase in the content of urea and protein carbonyl, while a decrease in the total protein, glucose, cholesterol, triglycerides, uric acid, and bilirubin was observed after the exposure. Hematological analysis revealed a decrease in the total erythrocyte count, hemoglobin, and partial pressure of oxygen, while there was an increase in the total leucocyte count, carbon dioxide, and partial pressure of carbon dioxide and serum electrolytes. Comet assay demonstrates a concentration-dependent increase in tail length, tail moment, olive tail moment, and percent tail DNA. An amino acid analyzer showed a TCS-dose-dependent increase in various amino acids. Sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis revealed different proteins ranging from 6.5 to 200 kDa, demonstrating TCS-induced upregulation. Fourier transform infrared spectra analysis exhibited a decline in peak area percents with an increase in the concentration of TCS in water. Curve fitting of amide I (1,700-1600 cm -1 ) showed a decline in α-helix and turns and an increase in β-sheets. Nuclear magnetic resonance study also revealed concentration-dependent alterations in the metabolites after 14 d exposure. TCS caused alterations in the biomolecules and heamatological parameters of fish, raising the possibility that small amounts of TCS may change the species richness in natural aquatic habitats. In addition, consuming TCS-contaminated fish may have detrimental effects on human health. Consequently, there is a need for the proper utilisation and disposal of this hazardous compound in legitimate quantities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gravitational field-flow fractionation (GrFFF) is a useful technique for separation and characterization for micrometer-sized particles. Elution behavior of micrometer-sized particles in GrFFF was researched in this study. Particles in GrFFF channel are subject to hydrodynamic lift forces (HLF), fluid inertial forces and gravity, which drive them to different velocities by carrier flow, resulting in a size-based separation. Effects of ionic strength, flow rate and viscosity as well as methanol were investigated using polystyrene latex beads as model particles. This study is devoted to experimental verification of the effect of every factor and their comprehensive function. All experiments were performed to show isolated influence of every variable factor. The orthogonal design test was used to evaluate various factors comprehensively. Results suggested that retention ratio of particles increases with increasing flow rate or the viscosity of carrier liquid by adjusting external forces acting on particles. In addition, retention ratio increases as ionic strength decreases because of decreased electrostatic repulsion between particles and channel accumulation wall. As far as methanol, there is no general trend due to the change of both density and viscosity. On the basis of orthogonal design test it was found that viscosity of carrier liquid plays a significant role in determining resolution of micrometer-sized particles in GrFFF., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Osteopontin (OPN) is a secreted, arginine-glycine-aspartic acid (RGD)-containing phosphoprotein proteolytically modified by members of the matrix metalloproteinase (MMP) family. We previously defined the MMP-3 and MMP-7 cleavage sites in OPN and found increased adhesive and migratory activity of a pool of MMP-cleaved fragments compared to full-length OPN. In the present study, we performed mutational analysis of recombinant full-length OPN and generated recombinant OPN fragments corresponding to the MMP-cleaved fragments, which have apparent molecular weights of 40, 32, and 25 kD by SDS-PAGE. Single residue mutations in 167L and 211L do not abrogate MMP cleavage although processing of the putative C-terminal fragment appears to be affected by a 167L to 167A mutation. The N-terminal 40-kD fragment was a stronger adhesive substrate compared to full-length OPN despite the observation that full-length OPN displayed greater binding in soluble phase to endothelial cell surfaces. While the 32-kD fragment showed significant binding to endothelial cell surfaces, the C-terminal 25-kD fragment did not interact with cell surface. Our data indicate that the increased adhesive activity of MMP-cleaved OPN was accountable by the N-terminal 40-kD fragment. We further analyzed receptor binding, using competition with peptides representing the alpha4beta1 and alpha9beta1 binding sites in the 40-kD N-terminal fragment. Using Jurkat cells, we found that a peptide corresponding to 131ELVTDFPTDLPATE144 had no effect on cell adhesion, whereas the peptide SVVYGLR competitively inhibited cell adhesion. These results suggest that a shorter motif that is found in MMP-cleaved OPN, 162SVVYG166, is sufficient to mediate cell adhesion of Jurkat cells to receptors, including the beta1 integrins, which have been previously characterized to bind the SVVYGLR sequence.