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Abstract Phase behaviours of two-dimensional (2D) systems constitute a fundamental topic in condensed matter and statistical physics. Although hard polygons and interactive point-like particles are well studied, the phase behaviours of more realistic molecular systems considering intermolecular interaction and molecular shape remain elusive. Here we investigate by molecular dynamics simulation phase stabilities of 2D ball-stick polygons, serving as simplified models for molecular systems. Below the melting temperature T m, we identify a critical edge number $${n}_{{{{\rm{c}}}}}=4$$ n c = 4 , at which a distorted square lattice emerges; when $$n \, < \, {n}_{{{{\rm{c}}}}}$$ n < n c , the triangular system stabilizes at a spin-ice-like glassy state; when $$n \, > \, {n}_{{{{\rm{c}}}}}$$ n > n c , the polygons stabilize at crystalline states. Moreover, in the crystalline state, T m is higher for polygons with more edges at higher pressures but exhibits a crossover for hexagon and octagon at low pressures. A theoretical framework taking into account the competition between entropy and enthalpy is proposed to provide a comprehensive understanding of our results, which is anticipated to facilitate the design of 2D materials.

Abstract Advanced identification of the potential sliding surface of a slope and accurate early warning are crucial prerequisites for effective management of landslides and timely and prevention of catastrophic accidents. This study analyzes the statistical characteristics of landslide displacement evolution. Based on the normal distribution theory, random variables of displacement velocity and acceleration with random errors are introduced into the analysis of surface displacement information, and random variables of relative displacement with random errors are introduced into the analysis of deep displacement information. When the random variables do not follow the normal distribution, the warning time can be obtained. Therefore, an advanced landslide classification warning method is established. The analysis results showed that analysis results from the April 30 landslide project at an open pit mine indicate that the earliest warning time for landslide initiation is 2020/2/19, while the earliest warnings for acceleration occur on 2020/4/15 and the fast acceleration on 2020/4/25. These three-level warning times align with reality, and the inferred slip surface position corresponds to the actual weak layer range. The primary power source driving landslide originates from behind the sliding body which subsequently pushes rock mass along weak layers near the south wing, north wing, and front in succession. Research findings can enhance landslide warning accuracy, facilitate advance identification of sliding surface, provide scientific basis for open-pit slope engineering design, as well as mitigate casualties and property losses.

We performed a stability analysis of a 2D wave-plate coupling system equipped with memory viscoelastic damping. The study highlights the unique functionality of the damping mechanism, which operates indirectly and exclusively within either the wave or plate subsystem. The opposing subsystem receives dissipative signals indirectly through the coupling component. The primary objective of this study was to determine whether the indirect memory damping is sufficient to ensure the overall stability of the coupled system. To address this question, a frequency domain analysis was employed to establish explicit decay rates of the coupled system. Notably, a polynomial decay rate is observed when the memory damping is applied solely to either the plate or wave subsystem, which provides a conclusive answer to the posed question.

Objectives: Proteus are known as opportunistic human pathogens that can cause a variety of infections. Proteus appendicitidis is a novel Proteus species associated with appendicitis, whereas their genomic characteristics and virulence potential remain understudied. This study aims to compare the genomic features of P. appendicitidis to that of the close Proteus species, and to assess its virulence-factor encoding capacity as an emerging pathogen. Methods: Genomes similar to that of P. appendicitidis HZ0627T were retrieved from the PATRIC-v3.6.10 web-server using the implanted Similar Genome Finder tool. Average nucleotide identity (ANI) between HZ0627T and the retrieved genomes was calculated using FastANI-v1.33. Core-genome sequences were extracted using Roary-v3.13.0, and core-genomic tree was constructed using FastTree-v2.1.11. Virulence-factor encoding capacity was predicted using PathoFact-v1.0. Results: Two previously unclassified Proteus sp. strains were reclassified as P. appendicitidis. Strains phylogenomically close to P. appendicitidis were clustered into five species, three of which were previously categorized under P. vulgaris biogroup 3. Remarkably, Proteus genomosp. 6 was identified as the closest species to P. appendicitidis, exhibiting ANI values ranging from 94.45 % to 94.95 % against HZ0627T. Genome annotation revealed shared genomic features and antimicrobial resistance (AMR) genes between P. appendicitidis and its phylogenetic neighbors. Additionally, P. appendicitidis is hypothesized to share infection mechanisms with Proteus genomosp. 6, as evidenced by the encoding of numerous virulence factors implicated in cell lysis and membrane pore-formation in the genome of both species. Conclusions: This study provides genomic insights of P. appendicitidis sp. nov. and its taxonomic relatives, shedding light on their evolutionary relationships, pathogenic mechanisms, and AMR profiles. The findings are significant for the development of targeted therapeutic interventions against infections caused by this emerging pathogen.

BackgroundThe consumption of sugar-sweetened beverages (SSBs) has become a major public health problem globally. However, no studies have specifically examined the relationship between SSB intake and chronic low back pain (CLBP). Therefore, the present study aimed to investigate the relationship between SSB intake and the risk of CLBP.MethodsThis cross-sectional study enrolled participants aged 20 to 69 from the National Health and Nutrition Examination Survey. CLBP was defined as persistent LBP for a consecutive three-month period. Furthermore, SSB intake was assessed and calculated based on dietary recall interviews. Moreover, survey-weighted logistic regression models were employed to evaluate the association between SSB intake and the risk of CLBP, while the restricted cubic spline (RCS) analysis was used to determine whether there were nonlinear associations between SSB intake and CLBP risk. In addition, subgroup analysis was performed using stratification and interaction analysis for all covariates.ResultsA total of 4,146 participants (mean age: 43.405 years) were enrolled in the final analysis. The results of survey-weighted logistic regression models showed that SSB consumption was significantly associated with an increased risk of CLBP among individuals aged 20 to 69 years. Moreover, the results of subgroup analysis and interaction analysis demonstrated that the association between SSB intake and the risk of CLBP was modified by smoking status and hypertension. Specifically, the SSB intake-associated CLBP risk was more pronounced among current smokers or individuals with hypertension.ConclusionReduction of SSB consumption might contribute to the prevention of CLBP for individuals aged 20 to 69 years. Moreover, current smokers or individuals with hypertension should be more vigilant about the SSB intake-associated CLBP risk. Nevertheless, caution should be exercised when interpreting the results of this study, as further research is necessary to explore the association between SSB consumption and CLBP, given the limitations of the current study.

AlkB homolog 1 (ALKBH1) is a member of the AlkB family of dioxygenases that are dependent on Fe(II) and α-ketoglutarate. Mounting evidence demonstrates that ALKBH1 exhibits enzymatic activity against various substrates, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), N3-methylcytidine (m3C), 5-methylcytosine (m5C), N6-methyladenine (N6-mA, 6mA), and H2A, indicating its dual roles in different biological processes and involvement in human diseases. Up to the present, there is ongoing debate regarding ALKBH1's enzymatic activity. In this review, we present a comprehensive summary of recent research on ALKBH1, including its substrate diversity and pathological roles in a wide range of human disorders, the underlying mechanisms of its functions, and its dysregulation. We also explored the potential of ALKBH1 as a prognostic target.

Abstract Background Topical photodynamic therapy (PDT) has demonstrated encouraging results in the treatment of oral leukoplakia (OLK). However, data on the clinical efficacy of PDT in Chinese patients with OLK are still limited. Methods Fifty patients diagnosed with OLK were enrolled, including patients with various dysplastic tissues. All patients received topical PDT with 5-aminolevulinic acid (5-ALA) as a photosensitizer. Clinical efficacy was evaluated 4 weeks after treatment. Follow-up was performed every 3 months during the first year and every 6 months during the second year. Results The overall response rate was 68% (34/50): 12% (n = 6) complete and 56% (n = 28) partial responses. Aneuploidy was reduced in the patients with dysplastic lesions. Oral pain and local ulcers developed in 52% of the patients (n = 26). Patients with a long history of OLK including hyperplasia and dysplastic lesions, as well as those with non-homogenous lesions, were more likely to develop pain and ulcer. During follow-up, the recurrence rate of hyperplasia and dysplastic lesions was 32% (n = 16) and the malignant transformation rate of dysplastic lesions was 4% (n = 2). Lesions on the buccal mucosa were associated with recurrence (P = 0.044; OR: 0.108, 95% CI: 0.013–0.915). Conclusion Topical 5-ALA-mediated PDT is an effective treatment for OLK, particularly for homogenous leukoplakia, with few side effects. The buccal mucosa may be a protective factor that can reduce recurrence.

The COVID-19 pandemic has changed the world and has presented the scientific community with unprecedented challenges. Infection is associated with overproduction of proinflammatory cytokines secondary to hyperactivation of the innate immune response, inducing a cytokine storm and triggering multiorgan failure and significant morbidity/mortality. No specific treatment is yet available. For thousands of years, Panax notoginseng has been used to treat various infectious diseases. Experimental evidence of P. notoginseng utility in terms of alleviating the cytokine storm, especially the cascade, and improving post-COVID-19 symptoms, suggests that P. notoginseng may serve as a valuable adjunct treatment for COVID-19 infection.

Abstract Background This study aims to explore the impacts of knowledge and attitude on the behavior of antibiotic use during the treatment of the common cold based on the expanding KAP model, and then identify the critical behavioral stage. Methods A cross-sectional study was conducted on 815 public from 21 community health centers (CHCs) in Chongqing, China. Based on the expanding KAP model, a self-administered questionnaire was designed to measure knowledge, attitude, multi-stage behavior, and perceived threat, in which multi-stage behavior was divided into pre-use antibiotic behavior, during-use antibiotic behavior, and post-use antibiotic behavior. A structural equation model was used to examine the model fit and the direct, indirect, mediating effects, and moderating effect of the variables. Results The expanding KAP showed good model fit indices with χ²/df = 0.537, RMSEA = 0.033, CFI = 0.973, GFI = 0.971, NFI = 0.934, TLI = 0.979. Knowledge had a positive effect on attitude (β = 0.503, p

Abstract Purpose Endotoxin-induced acute lung injury (ALI) is a severe disease caused by an imbalanced host response to infection. It is necessary to explore novel mechanisms for the treatment of endotoxin-induced ALI. In endotoxin-induced ALI, tetramethylpyrazine (TMP) provides protection through anti-inflammatory, anti-apoptosis, and anti-pyroptosis effects. However, the mechanism of action of TMP in endotoxin-induced ALI remains unclear. Here, we aimed to determine whether TMP can protect the lungs by inhibiting Golgi stress via the Nrf2/HO-1 pathway. Methods and results Using lipopolysaccharide (LPS)-stimulated C57BL/6J mice and MLE12 alveolar epithelial cells, we observed that TMP pretreatment attenuated endotoxin-induced ALI. LPS + TMP group showed lesser lung pathological damage and a lower rate of apoptotic lung cells than LPS group. Moreover, LPS + TMP group also showed decreased levels of inflammatory factors and oxidative stress damage than LPS group (P

Background: The prediction of fluid responsiveness in critical patients helps clinicians in decision making to avoid either under- or overloading of fluid. This study was designed to determine whether lung recruitment maneuver (LRM) would have an effect on the predictability of fluid responsiveness by the changes of hemodynamic parameters in pediatric patients who were receiving lung-protective ventilation and one-lung ventilation (OLV). Methods: A total of 34 children, aged 1–6 years old, scheduled for heart surgeries via right thoracotomy were enrolled. Patients were anesthetized and OLV with lung-protection ventilation settings was established, and then, positioned on left lateral decubitus. LRM and volume expansion (VE) were performed in sequence. Heart rate (HR), systolic arterial pressure (SAP), mean arterial pressure (MAP) diastolic arterial pressure (DAP), stroke volume (SV), stroke volume variation (SVV), and pulse pressure variation (PPV) were recorded via an A-line based monitor system at the following time points: before and after LRM (T1 and T2) and before and after VE (T3 and T4). An increase in stroke volume (SV) or mean arterial pressure (MAP) of ≥10% following fluid loading identified fluid responders. The predictability of fluid responsiveness by the changes of SV (ΔSVLRM) and MAP (ΔMAPLRM) after LRM and VE were statistically evaluated by receiver operating characteristic curves [area under the curves (AUC)]. Results: SVs in all patients were significantly decreased after LRM (p < 0.01) and then, increased and returned to baseline after VE (p < 0.01). In total, 16 out of 34 patients who were fluid responders had significantly lower SV after LRM compared to that in fluid non-responders. The area under the receiver operating characteristic curves for ΔSVLRM was 0.828 (95% confidence interval [CI], 0.660 to 0.935; p < 0.001) and it indicated that ΔSVLRM was able to predict the fluid responsiveness of pediatric patients. MAPs in all patients were also decreased significantly after LRM, and 12 of them fell into the category of fluid responders after VE. Statistically, ΔMAPLRM did not predict fluid responsiveness when LRM was considered as an influential factor (p = 0.07). Conclusions: ΔSVLRM, but not ΔMAPLRM, showed great reliability in the prediction of the fluid responsiveness following VE in children during one-lung ventilation with lung-protective settings. Trial registration: ChiCTR2300070690.

The use of bistatic polarimetric SAR for rough surface observation has attracted increasing interest in recent years, with its acquisition of additional polarimetric information. In this paper, we investigate the sensitivity of polarimetric variables to soil moisture and surface roughness, with the intention of locating favorable bistatic geometries for soil moisture retrieval. However, in the bistatic setting, the expanded imaging geometry is convolved with the polarimetric scattering response along with the in-scene variations in the soil moisture and surface roughness. The probing polarization states continuously evolve with the bistatic geometry, incurring varying polarization orientation angles. In this investigation, we propose to first compensate the bistatic polarimetric observations for the geometry-induced polarization rotation. Simulations based on a two-scale rough surface scattering model are then used to evaluate the optimal imaging geometry for the best sensitivity to the soil moisture content. We show the different sensing geometries associated with a full list of common polarimetric variables, as we seek favorable bistatic geometries in non-specular directions. The influences of both surface roughness scales are evaluated, with the small-scale roughness parameter imposing the greatest limitation on our results.

Cancer has long been a topic of great interest in society and a major factor affecting human health. Breast, prostate, lung, and colorectal cancers are the top four tumor types with the greatest incidence rates in 2020, according to the most recent data on global cancer incidence. Among these, lung cancer had the highest fatality rate. Extensive research has shown that microRNAs, through different signaling pathways, play crucial roles in cancer development. It is considered that the PI3K/AKT signaling pathway plays a significant role in the development of lung cancer. MicroRNAs can act as a tumor suppressor or an oncogene by altering the expression of important proteins in this pathway, such as PTEN and AKT. In order to improve the clinical translational benefit of microRNAs in lung cancer research, we have generalized and summarized the way of action of microRNAs linked with the PI3/AKT signaling pathway in this review through literature search and data analysis.

BackgroundImproving the rural residents’ accessibility to and affordability of health care is recognized as a common target globally. The Health in All Policies approach, from the Declaration of Helsinki to the United Nations’ Decade Of Healthy Ageing, strengthened the far-reaching effect of large-scale public policies on health care–seeking behavior; however, the effects of national transport policy on health care–seeking behavior is unclear. ObjectiveThis quasi-experimental study aimed to examine the effects of the implementation of transport-driven poverty alleviation (TPA) policy on health care–seeking behavior and medical expenditure among older adults in rural areas and the mechanism underlying these effects. MethodsWe designed a quasi-experiment to estimate the effects of TPA policy implementation on health care–seeking behavior and medical expenditure among older adults in rural areas through a difference-in-differences (DID) analysis based on data from the China Health and Retirement Longitudinal Study in 2011, 2013, 2015, and 2018. The underlying mechanism was analyzed and effect modification patterns were further investigated by poor households, health status, and age. ResultsOur findings validated a positive contribution of TPA policy on health care–seeking behavior among older adults in rural areas. After the implementation of TPA policy, the number of inpatient visits increased by annually 0.35 times per person, outpatient medical expenditure increased by 192% per month, and inpatient medical expenditure increased by 57% annually compared with those of older adults in rural areas without the implementation of TPA policy. Further, there was a significant modification effect, with a positive effect among poor households, healthier older adults, and those aged 60-80 years. Additionally, the policy improved the patients’ capabilities to seek long-distance care (β=23.16, 95% CI –0.99 to 45.31) and high-level hospitals (β=.08, 95% CI –0.02 to 0.13), and increased individual income to acquire more medical services (β=4.57, 95% CI –4.46 to 4.68). ConclusionsThese findings validate the positive contribution of TPA policy on health care–seeking behavior among older adults in rural areas; however, the medical expenditure incurred was also high. Concerted efforts are needed to address health care–seeking dilemmas in rural areas, and attention must be paid to curbing medical expenditure growth for older adults in rural areas during TPA policy implementation.

Lignocellulose recalcitrance hampers its utilization for the production of biofuels and biosourced chemicals. Here, the authors reveal that the amorphous cellulose is the breakpoint of interact microfibrils and propose OsFC16/CESA9 as the engineering target to increase saccharification ability.

Accurate measurement and interpretation of serum levels of troponin (Tn) is a central part of the clinical workup of a patient presenting with chest pain suspicious for acute coronary syndrome (ACS). Knowledge of the molecular characteristics of the troponin complex and test characteristics of troponin measurement assays allows for a deeper understanding of causes of false positive and false negative test results in myocardial injury. In this review, we discuss the molecular structure and functions of the constituent proteins of the troponin complex (TnT, TnC, and TnI); review the different isoforms of Tn and where they are from; survey the evolution of clinical Tn assays, ranging from first-generation to high-sensitivity (hs); provide a primer on statistical interpretation of assay results based on different clinical settings; and discuss potential causes of false results. We also summarize the advances in technologies that may lead to the development of future Tn assays, including the development of point of care assays and wearable Tn sensors for real-time continuous measurement.

Abstract Esophageal squamous cell carcinoma (ESCC) is characterized by high morbidity and mortality. Circular RNAs (circRNAs) play an important role in tumor progression. We discovered an aberrantly expressed circRNA (hsa_circ_0021727) in patients with ESCC. However, the mechanism of action of hsa_circ_0021727 in tumors is unclear. The present study aimed to investigate the biological role of hsa_circ_0021727 and its mechanism in ESCC progression. We screened for the expression of hsa_circ_0021727 in ESCC patients. Patients with ESCC with high expression of hsa_circ_0021727 had shorter survival than those with low expression. Hsa_circ_0021727 promoted the proliferation, invasion, and migration of ESCC cells. However, miR-23b-5p inhibited this ability of hsa_circ_0021727. MiR-23b-5p acts by targeting TAK1-binding protein 1 (TAB1). Upregulation of TAB1 can activate the nuclear factor kappa B (NFκB) pathway. Hsa_circ_0021727 promoted ESCC progression by activating TAB1/NFκB pathway by sponging miR-23b-5p. In addition, in vivo experiments also confirmed that hsa_circ_0021727 could promote the proliferation, invasion, and migration of ESCC cells. In short, hsa_circ_0021727 promotes ESCC progression by targeting miR-23b-5p to activate the TAB1/NFκB pathway. These findings might provide potential targets to treat ESCC.

Abstract Conventional resistive gate driving circuits suffer from significant recovery gate driving losses, especially at MHz ranges. The increasing gate driving losses brought by high switching frequency place a limitation to the high power density converter design. This paper proposes a novel floating resonant gate driver which maintains high efficiency at several megahertz operating frequency. The gate loss reduction is achieved by adopting a resonant process with driving power recycling. Part of the gate driving power can be recycled to a gate driving capacitor in the gate driving loop during charging and discharging. The proposed gate driver merges the merits of fast switching speed and low gate driving losses. A prototype of LLC power converter with the proposed floating resonant gate driver operating at 3.5 MHz is implemented. According to the experimental verification, the proposed gate driver realized a driving loss reduction by 70% and theoretical analysis is in good agreement with experimental results.

Objective To explore the role and value of applied muscle tension (AMT) in preventing vasovagal nerve reaction (VVR) in blood donors. Methods A total of 2 992 people, susceptible to suffer VVR from May 2020 to may 2022, were randomly divided into control group (1406 cases) and observation group (1 586 cases). The control group was not given AMT intervention, while the observation group received AMT intervention at different periods during blood donation. The changes of systolic blood pressure, diastolic blood pressure, heart rate and psychological state of anxiety (self-rating anxiety scale, SAS) of blood donors were monitored in the two groups at each period to compare the occurrence of VVR. Results There were no statistically significant differences in blood pressure and heart rate between the two groups before blood donation (P>0.05). The parameters were relatively stable in observation group during and after donation, but significantly different from that of the controls(P>0.05). SAS score was similar in two groups before blood donation(P>0.05), while decreased in observation group during and after donation in comparison with the controls(P

BackgroundChronic pain, sleep disorders, and depression are major global health concerns. Recent studies have revealed a strong link between sleep disorders and pain, and each of them is bidirectionally correlated with depressive symptoms, suggesting a complex relationship between these conditions. Social participation has been identified as a potential moderator in this complex relationship, with implications for treatment. However, the complex interplay among sleep disorders, pain, depressive symptoms, and social participation in middle- and old-aged Asians remains unclear. ObjectiveThis study aimed to examine the bidirectional relationship between sleep disorders and pain in middle- and old-aged Chinese and measure the role of depression as a mediator and social participation as a moderator in this bidirectional relationship through a dynamic cohort study. MethodsWe used data from the China Health and Retirement Longitudinal Study across 5 years and included a total of 7998 middle- and old-aged people (≥45 years old) with complete data in 2011 (T1), 2015 (T2), and 2018 (T3). The cross-lag model was used to assess the interplay among sleep disorders, pain, depressive symptoms, and social participation. Depressive symptoms were assessed by the 10-item Centre for Epidemiological Studies Depression scale. Sleep disorders were assessed by a single-item sleep quality scale and nighttime sleep duration. The pain score was the sum of all pain locations reported. Social participation was measured using self-reported activity. ResultsOur results showed significant cross-lagged effects of previous sleep disorders on subsequent pain at T2 (β=.141; P

Abstract Most of the current bioadhesives cannot perform well on bleeding tissues while postoperative adhesion is a general but serious clinical issue. Here, a three‐layer biodegradable Janus tissue patch (J‐TP) that is able to simultaneously enable efficient closure of bleeding wounds with significantly promoted clotting ability and suppressed postoperative adhesion of tissues is reported. A dry adhesive hydrogel bottom layer of the J‐TP can form rapid (within 15 s) and strong (tensile strength up to 98 kPa) adhesion to bleeding/wet tissues with high bursting pressure (about 312.5 mmHg on a sealed porcine skin) through hydrogen binding and covalent conjugation between the carboxyl & N‐hydroxy succinimide (NHS) groups of hydrogel and the primary amine groups of tissues, while the phosphonic motifs can significantly reduce blood loss (by 81% on a rat bleeding liver model) of bleeding wounds. A thin polylactic acid (PLA) middle layer can improve the tensile strength (by 132%) of the J‐TP in wet conditions while the grafted zwitterionic polymers can effectively prevent postoperative tissue adhesion and inflammatory reaction. This J‐TP may be a promising tissue patch to assist the clinical treatment of injured bleeding tissues with inhibited postoperative adhesion.

Background and AimsAnesthetics such as propofol, esketamine and nalbuphine are used during the upper gastrointestinal endoscopy to achieve and maintain the desired sedation level. The aim of the study was to evaluate the effectiveness and safety of propofol-nalbuphine and propofol-esketamine in children.MethodsA multi-centered study was performed at three tertiary class-A hospitals. Children between 3 and 12 years old undergoing diagnostic painless upper gastrointestinal endoscopy were included and randomly divided into esketamine or nalbuphine group to estimate the primary outcome of successful endoscope insertion. The patients were given esketamine 0.5 mg/kg and propofol 2 mg/kg intravenously in esketamine group, with nalbuphine 0.2 mg/kg and propofol 2 mg/kg in the nalbuphine group. The primary outcome was success rate for the first attempt of endoscope insertion in each group. Secondary outcomes included the safety of both anesthesia regimens and gastroenterologist's satisfaction. We used the Face, Leg, Activity, Cry and Consolability (FLACC) scale to evaluate the level of pain before and during the procedure and the Pediatric Anesthesia Emergence Delirium (PAED) scale to assess the level of agitation and delirium after awakening from anesthesia.ResultsAmong 246 patients, 200 were randomly included in the final intention-to-treat analysis, with 100 patients in each group. The success rate for the first attempt of endoscope insertion in the esketamine group was higher than the nalbuphine group (97% vs. 66%; P

Lipid droplets (LDs) are intracellular organelles that play important roles in cellular lipid metabolism; they change their sizes and numbers in response to both intracellular and extracellular signals. Changes in LD size reflect lipid synthesis and degradation and affect many cellular activities, including energy supply and membrane synthesis. Here, we focused on the function of the endoplasmic reticulum–plasma membrane tethering protein Ice2 in LD dynamics in the fungal pathogen Candida albicans (C. albicans). Nile red staining and size quantification showed that the LD size increased in the ice2Δ/Δ mutant, indicating the critical role of Ice2 in the regulation of LD dynamics. A lipid content analysis further demonstrated that the mutant had lower phosphatidylcholine levels. As revealed with GFP labeling and fluorescence microscopy, the methyltransferase Cho2, which is involved in phosphatidylcholine synthesis, had poorer localization in the plasma membrane in the mutant than in the wild-type strain. Interestingly, the addition of the phosphatidylcholine precursor choline led to the recovery of normal-sized LDs in the mutant. These results indicated that Ice2 regulates LD size by controlling intracellular phosphatidylcholine levels and that endoplasmic reticulum–plasma membrane tethering proteins play a role in lipid metabolism regulation in C. albicans. This study provides significant findings for further investigation of the lipid metabolism in fungi.

Abstract Background The pathogenesis of neuropathic pain and the reasons for the prolonged unhealing remain unknown. Increasing evidence suggests that sex oestrogen differences play a role in pain sensitivity, but few studies have focused on the oestrogen receptor which may be an important molecular component contributing to peripheral pain transduction. We aimed to investigate the impact of oestrogen receptors on the nociceptive neuronal response in the dorsal root ganglion (DRG) and spinal dorsal horn using a spared nerve injury (SNI) rat model of chronic pain. Methods We intrathecally (i.t.) administered a class of oestrogen receptor antagonists and agonists intrathecal (i.t.) administrated to male rats with SNI or normal rats to identify the main receptor. Moreover, we assessed genes identified through genomic metabolic analysis to determine the key metabolism point and elucidate potential mechanisms mediating continuous neuronal sensitization and neuroinflammatory responses in neuropathic pain. The excitability of DRG neurons was detected using the patch-clamp technique. Primary culture was used to extract microglia and DRG neurons, and siRNA transfection was used to silence receptor protein expression. Immunofluorescence, Western blotting, RT-PCR and behavioural testing were used to assess the expression, cellular distribution, and actions of the main receptor and its related signalling molecules. Results Increasing the expression and function of G protein-coupled oestrogen receptor (GPER), but not oestrogen receptor-α (ERα) and oestrogen receptor-β (ERβ), in the DRG neuron and microglia, but not the dorsal spinal cord, contributed to SNI-induced neuronal sensitization. Inhibiting GPER expression in the DRG alleviated SNI-induced pain behaviours and neuroinflammation by simultaneously downregulating iNOS, IL-1β and IL-6 expression and restoring GABAα2 expression. Additionally, the positive interaction between GPER and β-alanine and subsequent β-alanine accumulation enhances pain sensation and promotes chronic pain development. Conclusion GPER activation in the DRG induces a positive association between β-alanine with iNOS, IL-1β and IL-6 expression and represses GABAα2 involved in post-SNI neuropathic pain development. Blocking GPER and eliminating β-alanine in the DRG neurons and microglia may prevent neuropathic pain development.

Abstract Aims Opioid addiction is a major public health issue, yet its underlying mechanism is still unknown. The aim of this study was to explore the roles of ubiquitin–proteasome system (UPS) and regulator of G protein signaling 4 (RGS4) in morphine‐induced behavioral sensitization, a well‐recognized animal model of opioid addiction. Methods We explored the characteristics of RGS4 protein expression and polyubiquitination in the development of behavioral sensitization induced by a single morphine exposure in rats, and the effect of a selective proteasome inhibitor, lactacystin (LAC), on behavioral sensitization. Results Polyubiquitination expression was increased in time‐dependent and dose‐related fashions during the development of behavioral sensitization, while RGS4 protein expression was not significantly changed during this phase. Stereotaxic administration of LAC into nucleus accumbens (NAc) core inhibited the establishment of behavioral sensitization. Conclusion UPS in NAc core is positively involved in behavioral sensitization induced by a single morphine exposure in rats. Polyubiquitination was observed during the development phase of behavioral sensitization, while RGS4 protein expression was not significantly changed, indicating that other members of RGS family might be substrate proteins in UPS‐mediated behavioral sensitization.

BackgroundConducting geriatric trials is the most feasible way to address the vast underrepresentation of older adults in clinical trials of cancer therapies. This study is a globally comprehensive examination of geriatric trials for solid tumor worldwide over the last decade.MethodsUp-to-date information on cancer drug trials in older adults aged over 59 years from the beginning of 2012 to the end of 2021 was collected from Trialtrove and Pharmaprojects. The number of identified trials was the dependent variable and corresponding analysis was conducted from the perspective of time trend, status quo and comparisons by region and country, sponsor type and cancer type, study status and phase.ResultsA total of 292 geriatric cancer drug trials were identified, of which 287 were single-region studies, 219 were initiated by academic groups, and 55 (18.8%) were terminated. Decreasing trends in the annual number of all trials (−9.2% per year) and the annual number of trials by academic groups (−9.4%) were observed over time. Of the geriatric trials, 183 were conducted in Asia; this number was significantly higher than that in Europe (74), North America (37), Oceania (4), and South America (1). Similar difference was found in participation rate in trials by academic groups ranging from 71.7% in Asia to 0.5% in South America. Of the trials, 19 and 97 were initiated before drug and indication approval, respectively, and the remaining 176 were initiated after indication approval. Phase II trials accounted for the highest proportion of trials (213, 72.9%), while phase I trials accounted for the lowest proportion (14, 4.8%). Trials by academic groups had a higher termination rate (21.5% vs. 11.0%) and fewer were phase IV trials (8.2% vs. 21.9%). Treatment was explored for 16 different cancers, with lung, colorectal and breast cancers being the most common.ConclusionGeriatric trials of solid tumor drugs are scarce and partially prematurely terminated. Moreover, the number of geriatric trials has decreased and differs according to region. Global guidance and regulatory supervision are needed to facilitate the acquisition of adequate evidence on drug risk-benefit profiles in older adults, and thus to achieve high-quality care and safe medication.

Abstract The stability of an inner dump slope was investigated under the effect of coal pillar support considering the development position of dumping. Based on the instability mechanism and load distribution characteristics of the supporting coal pillar, the three-dimensional mechanical effects of the supporting coal pillar are characterized. Using the two-dimensional equivalent principle and the residual thrust method, the stability of the inner dump slope was analyzed under the effect of pillar support at different dump development positions. The quantitative effects of various factors on the inner dump slope stability were revealed, and the coal pillar shape parameters were optimized through numerical simulations. The results indicate that the slope stability coefficient is linearly related to the top width and height of the coal pillar, slope angle, and base inclination angle, and has an exponential relation with the coal pillar strike length and slope height increment. There are quadratic and absolute value relations with the coal pillar outer and the inner bottom angle, respectively. The top width of the coal pillar in the inner dump of Shengli East No.2 open-pit coal mine should be at a level of + 824 m, and the optimal top width and height are 15 and 36.7 m, respectively. The instability mechanism of the supporting and retaining coal pillar obtained by numerical simulations and the stability of the inner dump are in good agreement with the theoretical analysis. Our results provide a theoretical basis for the design, treatment, and safe implementation of similar open-pit mine slope engineering.

Abstract Clarifying the shear creep characteristics of rock and scientifically analyzing its creep deformation law is the key to solving the problem of safe construction and long-term stability analysis of the open-pit coal slope rock mass. Shear creep tests were carried out on mudstone from an open-pit coal mine in Eastern Mongolia to reveal the creep characteristics of mudstone under different normal and shear stresses. Based on the classical Nishihara model, a new composite six-element nonlinear shear creep damage model is established by introducing nonlinear elastomers. Using the least square method, model verification and parameter identification are carried out on the variable test data. At the same time, the influence law of the model parameters on the rock creep deformation is analyzed according to the theoretical curve. The study results showed that the nonlinear shear creeps damage model could better describe the creep characteristics of rock different normal stress and shear stress levels, significantly the non-linear both the strain and time of attenuation creep and accelerated creep. The creep characteristics of the accelerated creep stage described by this model are better than those described by the classical Nishihara model. The model curve is consistent with the changing trend of the experimental data, and the degree of agreement is very high. The correlation coefficients are all above 0.98, which verifies the accuracy and rationality of the model. The influence law of creep parameters is analyzed. The parameters b and c increase nonlinearly with creep. The increase of λ accelerates the process of rock attenuation creep stage; the increase of η 10 slows down the progress of rock decay creep stage; with the increase of α, the deformation and creep rate of rock in accelerated creep stage gradually increase. When η 2 increases, the deformation in the acceleration stage decreases gradually. The research results can provide important theoretical support for the safe construction and long-term stability analysis of open-pit coal slope rock masses.

The IEEE 802.11 standard provides multi-rate support for different versions. As there is no specification on the dynamic strategy to adjust the rate, different rate adaptation algorithms are applied according to different manufacturers. Therefore, it is often hard to interpret the performance discrepancy of various devices. Moreover, the ever-changing channels always challenge the rate adaptation, especially in the scenario with scarce spectrum and low SNR. As a result, it is important to sense the radio environment cognitively and reduce the unnecessary oscillation of the transmission rate. In this paper, we propose an environment-aware robust (EAR) algorithm. This algorithm employs an occasional small packet, designs a rate scheme adaptive to the environment, and enhances the robustness. We verify the throughput of EAR using network simulator NS-3 in terms of station number, motion speed and node distance. We also compare the proposed algorithm with three benchmark methods: AARF, RBAR and CHARM. Simulation results demonstrate that EAR outperforms other algorithms in several wireless environments, greatly improving the system robustness and throughput.

Water transport through membranes is an attractive topic among the research dedicated to dehydration processes, microenvironment regulation, or more simply, recovery of freshwater. Herein, an atomistic computer simulation is proposed to provide new insights about a water vapor transport mechanism through PEBAX membranes filled with ionic liquid (IL) [C12C1im]Cl. Starting from experimental evidence that indicates an effective increase in water permeation as the IL is added to the polymer matrix (e.g., up to 85·10−3 (g·m)/(m2·day) at 318.15 K for PEBAX@2533 membranes loaded with 70% of IL), molecular dynamics simulations are proposed to explore the key role of IL in water transport inside membranes. The polar region composed of anions and cationic head groups of the IL is demonstrated to serve as the pathway for water transport through the membrane. Water molecules always stay near the pathway, which becomes wider and thus has a larger water-accessible area with increasing IL concentration. Hence, the diffusion coefficients of water molecules and ions increase as the IL concentration increases. The simulation provides useful indications about a microscopic mechanism that regulates the transport of water vapor through a kind of PEBAX/IL membrane, resulting in full agreement with the experimental evidence.

Estimation of polarization orientation angle (POA) is of general interest in polarimetric SAR (PolSAR) image processing because it is useful to remove the orientation-induced polarimetric distortion but also to infer physical target parameters. Under the assumption of scatter reflection symmetry, POA can be readily estimated from a circular polarization basis formulation or equivalently from zeroing the Pauli-basis correlation term ${{\boldsymbol{T}}}_{23}$. This solution does not account for a possible presence of helical components; alternatively, we developed a general formulation for POA estimation using Touzi parameterization that explicitly contains a helical angle. When applied to PolSAR imagery of rough terrain surface, those two estimators generally give different results. Based on the POA derived from coregistered digital elevation model data, we find the former estimator can underestimate the POA for rough terrain surface. In this article, we further investigate the underlying cause. Although these two POA estimators differ in whether assuming zero helicity or not, the inherent helicity on the rough surface scattering is negligible; instead, the difference in the estimated POA is mainly attributed to the degree of mixing of a secondary scattering mechanism. This mixing impact can be significant even for rough terrain with only light vegetation cover, suggesting a practical need for inclusion of alternative estimators.

Abstract Oral lichen planus (OLP) is a localized autoimmune disease of the oral mucosa, with an incidence of up to 2%. Although corticosteroids are the first-line treatment, they cause several adverse effects. Quercetin, a naturally occurring compound, has fewer side-effects and provides long-term benefits. Besides, it has powerful anti‑inflammatory activities. Here, we combined network pharmacology with experimental verification to predict and verify the key targets of quercetin against OLP. First, 66 quercetin-OLP common targets were analyzed from various databases. The protein–protein interaction (PPI) network was constructed. Topology analysis and MCODE cluster analysis of common targets were conducted to identify 12 key targets including TP53, IL-6 and IFN-γ and their connections. Gene functions and key signaling pathways, including reactive oxygen species metabolism, IL-17 pathway and AGE-RAGE pathway, were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, in vitro experiments showed that quercetin interfered with Th1/Th2 balance by acting on IL-6 and IFN-γ to modulate the immune system in treating OLP. Quercetin considerably affected the apoptosis and migration of T lymphocytes in OLP patients. Our study reveals the potential therapeutic targets and signaling pathways of quercetin associated with OLP, and establishes the groundwork for future clinical applications.

Proactive project scheduling aims to generate robust baseline schedules that are protected against the potential schedule disruptions during project execution. In this paper, we propose a new problem named the proactive resource-constrained project scheduling problem with activity splitting and resource transfer times, and try to investigate the trade-off between the benefits of activity splitting and the drawbacks of the resulting more resource transfer times. The proposed problem is formulated into an integer programming model with considering the constraints of a maximum allowed number of splitting and a minimum period of continuous execution. Since the problem is NP-hard in the strong sense, a genetic algorithm is then developed for problem solving. From the obtained results of a designed computational experiment, we prove that the developed genetic algorithm is effective in solving the defined problem, and the benefits of activity splitting to schedule robustness improvement can be weaken with the resulting more resource transfer times among the subactivities. Besides, with the increase of the maximum allowed number of activity splitting, the decrease of the minimum continuous execution time, the decrease of resource transfer times, and the extension of project deadlines, schedule robustness increases.

In areas with large differences between day and night temperature, the freeze-thaw cycle and frost heaving force in rock mass generate cracks within the rock, which seriously threatens the stability and safety of geotechnical engineering structures and surrounding buildings. This problem can be solved by developing a reasonable model that accurately represents the rock creep behavior. In this study, we developed a nonlinear viscoelastic-plastic creep damage model by introducing material parameters and a damage factor while connecting an elastomer, a viscosity elastomer, a Kelvin element, and a viscoelastic-plastic element in series. One- and three-dimensional creep equations were derived, and triaxial creep data were used to determine the model parameters and to validate the model. The results showed that the nonlinear viscoelastic-plastic creep damage model can accurately describe rock deformation in three creep stages under freeze-thaw cycles. In addition, the model can describe the time-dependent strain in the third stage. Parameters G1, G2, and η20' decrease exponentially with the increase in the number of freeze-thaw cycles while parameter λ increases exponentially. These results provide a theoretical basis for studying the deformation behavior and long-term stability of geotechnical engineering structures in areas with large diurnal temperature differences.

Background. Transcatheter aortic valve replacement (TAVR) is known to increase the incidence of conduction disturbances compared to surgical aortic valve replacement; however, there are limited data on the impact and duration of these conduction disturbances on longer term outcomes. Objective. To determine the differential impact of persistent versus nonpersistent new-onset conduction disturbances on TAVR-related complications and outcomes. Methods. This is a single-center retrospective analysis of 927 consecutive patients with aortic stenosis who underwent TAVR at Yale New Haven Hospital from July 2012 to August 2019. Patients with new-onset conduction disturbances within 7 days following TAVR were selected for this study. Persistent and nonpersistent disturbances were, respectively, defined as persisting or not persisting on all patient ECGs for up to 1.5 years after TAVR or until death. Results. Within 7 days after TAVR, conduction disturbances occurred in 42.3% (392/927) of the patients. Conduction disturbances persisted in 150 (38%) patients and did not persist in 187 (48%) patients, and 55 (14%) patients were excluded for having mixed (both persistent and nonpersistent) disturbances. Compared with nonpersistent disturbances, patients with persistent disturbances were more likely to receive a PPM within 7 days after the TAVR procedure (46.0% versus 4.3%, p

Abstract The creep characteristics of rock under step loading and unloading conditions were investigated in this study. Based on the generalized Burgers model, the total strain of rock was decomposed into elastic, viscoelastic, varying-parameter viscoelastic, and viscoplastic strains considering the damage. The four strains were connected in series to establish a new varying-parameter creep damage model that can characterize the creep characteristics of rock under step loading and unloading conditions as well as identify and verify the model parameters. The study results showed that the varying-parameter creep damage model could better describe the creep characteristics of rock under step loading and unloading conditions, significantly the non-linear both the strain and time of attenuation creep and accelerated creep. The model fitting curve was highly consistent with the experimental data, and the correlation coefficient R 2 was greater than 0.98, which thoroughly verified the accuracy and rationality of the model. These findings can provide theoretical support for analyzing the deformation and long-term stability of rock and soil.

Abstract Background As a major component of plant cell walls, cellulose provides the most abundant biomass resource convertible for biofuels. Since cellulose crystallinity and polymerization have been characterized as two major features accounting for lignocellulose recalcitrance against biomass enzymatic saccharification, genetic engineering of cellulose biosynthesis is increasingly considered as a promising solution in bioenergy crops. Although several transcription factors have been identified to regulate cellulose biosynthesis and plant cell wall formation, much remains unknown about its potential roles for genetic improvement of lignocellulose recalcitrance. Results In this study, we identified a novel rice mutant (Osfc9/myb103) encoded a R2R3-MYB transcription factor, and meanwhile generated OsMYB103L-RNAi-silenced transgenic lines. We determined significantly reduced cellulose levels with other major wall polymers (hemicellulose, lignin) slightly altered in mature rice straws of the myb103 mutant and RNAi line, compared to their wild type (NPB). Notably, the rice mutant and RNAi line were of significantly reduced cellulose features (crystalline index/CrI, degree of polymerization/DP) and distinct cellulose nanofibers assembly. These alterations consequently improved lignocellulose recalcitrance for significantly enhanced biomass enzymatic saccharification by 10–28% at p

With the rapid development of wearable electronic products and smart devices, there is an urgent need to develop efficient electromagnetic interference (EMI)shielding materials to eliminate the resulting radiation pollution. Herein, hydrophobic and multi-responsive conductive composite film with core-shell structure and sandwich structure are constructed via simple in-situ polymerization and dip coating methods. The thin silicone coating can enhance the bonding fastness of the substrate and the conductive functional layer and endow the composite film excellent waterproof performance. The composite film with a thickness of 45 μm exhibits outstanding electrical conductivity of 62.15 S/cm and EMI shielding effectiveness (EMI SE) of 37.71 dB. Surprisingly, the composite film also exhibits good waterproof performance and excellent electro-optical thermal response, and has good stability in complex environments. This work proves the advantages of constructing multiple conductive interfaces inside the nanofiber film, and provides a new preparation strategy for efficient multifunctional shielding materials, which is expected to be widely used in the next generation of wearable electronic devices and wearable smart clothing.

Purpose: To establish a pharmacist-led olaparib follow-up program for ovarian cancer patients, provide patient education, get information on adverse drug reactions (ADRs), and identify and manage drug-related problems.Methods: Ambulatory adult patients with ovarian cancer receiving olaparib were enrolled. At least one follow-up session was conducted by clinical pharmacists. Pharmacists collected data on the type and grade of ADRs, drug adherence, olaparib dosing, concomitant medications, and pharmacists’ suggestions.Results: 83 patients were enrolled with the median age of 58. The average number of the follow-up sessions provided to each patient was 1.31, and the average duration of each follow-up was 17.78 min. The olaparib starting dose for most patients (97.59%) was 600 mg/d. 36.14% of the patients had missed olaparib doses and 27.71% of the patients had dose adjustments due to ADRs. The most common ADRs (incidence≥10%) were: fatigue (40.96%), anemia (36.14%), leukopenia (36.14%), nausea (28.92%), thrombocytopenia (16.87%), anorexia (16.87%), dyspepsia (15.66%). The tolerability profiles were generally similar between patients treated for “first-line maintenance” and those treated for “recurrence maintenance” (p > .05). There were 42% of the patients who were concomitantly taking medications without exact chemical contents (such as formulated Chinese medicines and Chinese decoctions), and common types of concomitant medications with exact drug names were antihypertensive, anti-hyperglycemic, and anti-hyperlipidemic medications. The pharmacists identified 4 clinically significant drug-drug interactions (DDIs) in two patients. Pharmacists made 196 suggestions mainly related to rational use of the medications and management of ADRs.Conclusion: The study provides the first report about pharmacist-led follow-up service for olaparib. The types of ADRs were similar to those previously observed in clinical trials, and the profiles of ADRs in different types of patients (first-line maintenance vs. recurrence maintenance) were also similar. Pharmacists identified drug-related problems (such as adherence, DDIs and management of ADRs) and offer suggestions for the patients.

Coastal areas are highly influenced by terrestrial runoffs and anthropogenic disturbances, commonly leading to ecological gradients from bay, nearshore, to offshore areas. Although the occurrence and distribution of sediment antibiotic resistome are explored in various coastal environments, little information is available regarding geographic patterns and determinants of coastal sediment antibiotic resistomes across ecological gradients at the regional scale. Here, using high-throughput quantitative PCR, we investigated the geographic patterns of 285 antibiotic resistance genes (ARGs) in coastal sediments across a ~ 200 km scale in the East China Sea. Sediment bacterial communities and physicochemical properties were characterized to identify the determinants of sediments antibiotic resistome. Higher richness and abundance of ARGs were detected in the bay samples compared with those in nearshore and offshore samples, and significant negative correlations between the richness and/or abundance of ARGs and the distance to coastline (DTC) were identified, whereas different types of ARGs showed inconsistency in their relationships with DTC. The composition of antibiotic resistome showed significant correlations with nutrition-related variables (including NH4+-N, NO3−-N, and total phosphorus) and metals/metalloid (including As, Cu, Ni, and Zn), suggesting that terrestrial disturbances largely shape the antibiotic resistome. The Bipartite network showed strong associations between ARGs and mobile genetic elements (MGEs), and Partial Least Squares Path Modeling further revealed that terrestrial disturbance strength (as indicated by DTC) directly affected abiotic environmental conditions and bacterial community composition, and indirectly affected antibiotic resistome via MGEs. These findings provide insights into regional variability of sediment antibiotic resistome and its shaping path across complex ecological gradients, highlighting terrestrial disturbances as determinative forces in shaping coastal sediment antibiotic resistomes.

Abstract SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF) plays dual roles in the initiation and development of human malignancies. However, the biological role of SPDEF in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, the expression level of SPDEF and its correlation with the clinical parameters of patients with HNSCC were determined using TCGA-HNSC, GSE65858, and our own clinical cohorts. CCK8, colony formation, cell cycle analysis, and a xenograft tumor growth model were used to determine the molecular functions of SPDEF in HNSCC. ChIP-qPCR, dual luciferase reporter assay, and rescue experiments were conducted to explore the potential molecular mechanism of SPDEF in HNSCC. Compared with normal epithelial tissues, SPDEF was significantly downregulated in HNSCC tissues. Patients with HNSCC with low SPDEF mRNA levels exhibited poor clinical outcomes. Restoring SPDEF inhibited HNSCC cell viability and colony formation and induced G0/G1 cell cycle arrest, while silencing SPDEF promoted cell proliferation in vitro. The xenograft tumor growth model showed that tumors with SPDEF overexpression had slower growth rates, smaller volumes, and lower weights. SPDEF could directly bind to the promoter region of NR4A1 and promoted its transcription, inducing the suppression of AKT, MAPK, and NF-κB signaling pathways. Moreover, silencing NR4A1 blocked the suppressive effect of SPDEF in HNSCC cells. Here, we demonstrate that SPDEF acts as a tumor suppressor by transcriptionally activating NR4A1 in HNSCC. Our findings provide novel insights into the molecular mechanism of SPDEF in tumorigenesis and a novel potential therapeutic target for HNSCC.

N6‐methyladenosine (m6A) has emerged as the most prevalent post‐transcriptional modification on mRNA that contributes prominently to tumorigenesis. However, the specific function of m6A methyltransferase methyltransferase‐like 3 (METTL3) in colorectal cancer (CRC) remains elusive. Herein, we explored the biological function of METTL3 in CRC progression. Clinically, METTL3 was frequently upregulated in CRC tissues, cell lines, and plasma samples and its high expression predicted poor prognosis of CRC patients. Functionally, knockdown of METTL3 significantly repressed CRC cell proliferation and migration in vitro, while its overexpression accelerated CRC tumor formation and metastasis both in vitro and in vivo. Mechanistically, METTL3 epigenetically repressed YPEL5 in an m6A‐YTHDF2‐dependent manner by targeting the m6A site in the coding sequence region of the YPEL5 transcript. Moreover, overexpression of YPEL5 significantly reduced CCNB1 and PCNA expression. Collectively, we identified the pivotal role of METTL3‐catalyzed m6A modification in CRC tumorigenesis, wherein it facilitates CRC tumor growth and metastasis through suppressing YPEL5 expression in an m6A‐YTHDF2‐dependent manner, suggesting a promising strategy for the diagnosis and therapy of CRC.

BackgroundSuccessful weaning and extubation after cardiac surgery is an important step of postoperative recovery. Delayed extubation is associated with poor prognosis and high mortality, thereby contributing to a substantial economic burden. The aim of this study was to develop and validate a prediction model estimate the risk of delayed extubation after cardiac surgery based on perioperative risk factors.MethodsWe performed a retrospective cohort study of adult patients undergoing cardiac surgery from 2014 to 2019. Eligible participants were randomly assigned into the development and validation cohorts, with a ratio of 7:3. Variables were selected using least absolute shrinkage and selection operator (LASSO) logistic regression model with 10-fold cross-validation. Multivariable logistic regression was applied to develop a predictive model by introducing the predictors selected from the LASSO regression. Receiver operating characteristic (ROC) curve, calibration plot, decision curve analysis (DCA) and clinical impact curve were used to evaluate the performance of the predictive risk score model.ResultsAmong the 3,919 adults included in our study, 533 patients (13.6%) experienced delayed extubation. The median ventilation time was 68 h in the group with delayed extubation and 21 h in the group without delayed extubation. A predictive scoring system was derived based on 10 identified risk factors based on 10 identified risk factors including age, BMI ≥ 28 kg/m2, EF < 50%, history of cardiac surgery, type of operation, emergency surgery, CPB ≥ 120 min, duration of surgery, IABP and eGFR < 60 mL/min/1.73 m2. According to the scoring system, the patients were classified into three risk intervals: low, medium and high risk. The model performed well in the validation set with AUC of 0.782 and a non-significant p-value of 0.901 in the Hosmer-Lemeshow test. The DCA curve and clinical impact curve showed a good clinical utility of this model.ConclusionsWe developed and validated a prediction score model to predict the risk of delayed extubation after cardiac surgery, which may help identify high-risk patients to target with potential preventive measures.

The use of green and sustainable biomass-derived compounds to obtain excellent electrochemical properties is important to address growing environmental and energy issues. In this paper, cheap and abundant watermelon peel was used as a raw material to successfully synthesize nitrogen-phosphorus double-doped bio-based porous carbon by a one-step carbonization method and explore it as a renewable carbon source for low-cost energy storage devices. The supercapacitor electrode exhibited a high specific capacity of 135.2 F/g at a current density of 1 A/g in a three-electrode system. A variety of characterization methods and electrochemical tests indicate that porous carbon prepared by this simple method has great potential as electrode materials for supercapacitors.

Abstract Background Phosphorus (P) is an essential macronutrient for plant growth and development. Upon P shortage, plant responds with massive reprogramming of transcription, the Phosphate Starvation Response (PSR). In parallel, the production of strigolactones (SLs)—a class of plant hormones that regulates plant development and rhizosphere signaling molecules—increases. It is unclear, however, what the functional link is between these two processes. In this study, using tomato as a model, RNAseq was used to evaluate the time-resolved changes in gene expression in the roots upon P starvation and, using a tomato CAROTENOID CLEAVAGE DIOXYGENASES 8 (CCD8) RNAi line, what the role of SLs is in this. Results Gene ontology (GO)-term enrichment and KEGG analysis of the genes regulated by P starvation and P replenishment revealed that metabolism is an important component of the P starvation response that is aimed at P homeostasis, with large changes occurring in glyco-and galactolipid and carbohydrate metabolism, biosynthesis of secondary metabolites, including terpenoids and polyketides, glycan biosynthesis and metabolism, and amino acid metabolism. In the CCD8 RNAi line about 96% of the PSR genes was less affected than in wild-type (WT) tomato. For example, phospholipid biosynthesis was suppressed by P starvation, while the degradation of phospholipids and biosynthesis of substitute lipids such as sulfolipids and galactolipids were induced by P starvation. Around two thirds of the corresponding transcriptional changes depend on the presence of SLs. Other biosynthesis pathways are also reprogrammed under P starvation, such as phenylpropanoid and carotenoid biosynthesis, pantothenate and CoA, lysine and alkaloids, and this also partially depends on SLs. Additionally, some plant hormone biosynthetic pathways were affected by P starvation and also here, SLs are required for many of the changes (more than two thirds for Gibberellins and around one third for Abscisic acid) in the gene expression. Conclusions Our analysis shows that SLs are not just the end product of the PSR in plants (the signals secreted by plants into the rhizosphere), but also play a major role in the regulation of the PSR (as plant hormone).

Abstract Background Identifying lignocellulose recalcitrant factors and exploring their genetic properties are essential for enhanced biomass enzymatic saccharification in bioenergy crops. Despite genetic modification of major wall polymers has been implemented for reduced recalcitrance in engineered crops, it could most cause a penalty of plant growth and biomass yield. Alternatively, it is increasingly considered to improve minor wall components, but an applicable approach is required for efficient assay of large population of biomass samples. Hence, this study collected total of 100 rice straw samples and characterized all minor wall monosaccharides and biomass enzymatic saccharification by integrating NIRS modeling and QTL profiling. Results By performing classic chemical analyses and establishing optimal NIRS equations, this study examined four minor wall monosaccharides and major wall polymers (acid-soluble lignin/ASL, acid-insoluble lignin/AIL, three lignin monomers, crystalline cellulose), which led to largely varied hexoses yields achieved from enzymatic hydrolyses after two alkali pretreatments were conducted with large population of rice straws. Correlation analyses indicated that mannose and galactose can play a contrast role for biomass enzymatic saccharification at P

Abstract Background Infertile women often face stigmatization worldwide. This study aimed to investigate the stigma against infertile women in China and to analyze its influencing factors. Methods Of 270 women who were randomly selected from patients receiving adjuvant fertility treatment in Zhejiang Province, China, 254 successfully completed the general information questionnaire, disease information questionnaire, and Chinese version of the infertility stigma scale (ISS). The ISS contained 27 positively worded items, each of which was graded on a 5-point Likert-type scale. Results The total stigma score of female infertility patients was 66.39 ± 21.96. By dividing the number of items, the average score for each ISS item was 2.13 ± 0.81, indicating the presence of stigma. Among the four ISS factors, the social withdrawal score was the highest (2.64 ± 1.05), whereas the family stigma score was the lowest (1.88 ± 0.88). Multiple stepwise regression analysis further revealed that the duration of infertility and monthly income were important predictors of the stigma of infertile women. Conclusions Infertile women experience moderate to high levels of stigma in Zhejiang, China. Thus, supportive psychological interventions and public education are required to change patients’ cognition and assist patients in coping with negative experiences.

Abstract Crop straws represent enormous biomass resource convertible for biofuels and bioproducts, but lignocellulose recalcitrance restricts its saccharification for commercial utility. Despite genetic modification of lignin biosynthesis being attempted to reduce recalcitrance in bioenergy crops, it remains challenging to optimize lignin deposition without an unacceptable yield penalty. Based on gene expression analysis and phylogenetic tree profiling, a cinnamyl alcohol dehydrogenase gene (OsCAD2) as the target for genetic engineering of lignin biosynthesis in rice was selected in this study. Using CRISPR/Cas9 technology, independent homozygous transgenic lines with precise site mutation of OsCAD2, which showed slightly reduced lignin levels but markedly decreased p‐hydroxyphenyl (H) contents in lignin by 34% and increased guaiacyl (G) contents by 16%, compared to the wild type were generated in this study. Under mild alkali pretreatment (1% NaOH, 50°C), the OsCAD2 site‐modified lines showed effective lignin extraction up to 70% (of total lignin) from mature rice straws, which caused either significantly increased biomass porosity and cellulose accessibility or remarkably reduced cellulase adsorption to lignin in pretreated lignocellulose residues. These consequently led to almost complete biomass enzymatic saccharification with increased hexoses yields by 61%–72% in the modified lines, being much higher than those of the lignin‐altered lines reported in previous studies. Hence, this study has demonstrated a novel genetic engineering strategy to reduce lignocellulose recalcitrance with minimized biomass loss for cost‐effective biomass conversion to bioethanol in rice and bioenergy crops.

The carbon materials derived from discarded masks and lignin are used as adsorbent to remove two types of reactive dyes present in textile wastewater: anionic and cationic. This paper introduces the results of batch experiments where Congo red (CR) and Malachite green (MG) are removed from wastewater onto the carbon material. The relationship between adsorption time, initial concentration, temperature and pH value of reactive dyes was investigated by batch experiments. It is discovered that pH 5.0–7.0 leads to the maximum effectiveness of CR and MG removal. The equilibrium adsorption capacities of CR and MG are found to be 232.02 and 352.11 mg/g, respectively. The adsorption processes of CR and MG are consistent with the Freundlich and Langmuir adsorption models, respectively. The thermodynamic processing of the adsorption data reveals the exothermic properties of the adsorption of both dyes. The results show that the dye uptake processes follow secondary kinetics. The primary adsorption mechanisms of MG and CR dyes on sulfonated discarded masks and alkaline lignin (DMAL) include pore filling, electrostatic attraction, π-π interactions and the synergistic interactions between the sulphate and the dyes. The synthesized DMAL with high adsorption efficiency is promising as an effective recyclable adsorbent for adsorbing dyes, especially MG dyes, from wastewater.

Cellulosic ethanol is regarded as a perfect additive for petrol fuels for global carbon neutralization. As bioethanol conversion requires strong biomass pretreatment and overpriced enzymatic hydrolysis, it is increasingly considered in the exploration of biomass processes with fewer chemicals for cost-effective biofuels and value-added bioproducts. In this study, we performed optimal liquid-hot-water pretreatment (190 °C for 10 min) co-supplied with 4% FeCl3 to achieve the near-complete biomass enzymatic saccharification of desirable corn stalk for high bioethanol production, and all the enzyme-undigestible lignocellulose residues were then examined as active biosorbents for high Cd adsorption. Furthermore, by incubating Trichoderma reesei with the desired corn stalk co-supplied with 0.05% FeCl3 for the secretion of lignocellulose-degradation enzymes in vivo, we examined five secreted enzyme activities elevated by 1.3–3.0-fold in vitro, compared to the control without FeCl3 supplementation. After further supplying 1:2 (w/w) FeCl3 into the T. reesei-undigested lignocellulose residue for the thermal-carbonization process, we generated highly porous carbon with specific electroconductivity raised by 3–12-fold for the supercapacitor. Therefore, this work demonstrates that FeCl3 can act as a universal catalyst for the full-chain enhancement of biological, biochemical, and chemical conversions of lignocellulose substrates, providing a green-like strategy for low-cost biofuels and high-value bioproducts.