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Abstract To compare the economic burden of disease and quality of life in patients with premature ejaculation (PE) and erectile dysfunction (ED). A convenience sampling method was used, and self-designed general information questionnaire, disease economic burden questionnaire, and SF-12 quality of life questionnaire were used to investigate 494 patients with ED and 285 patients with PE who attended a tertiary hospital in Taiyuan City from October 2021 to May 2023, and the relevant data were analysed using SPSS26.0 statistical software. The direct, indirect, intangible, and total economic burdens of the two groups were compared, and the differences were statistically significant (P

Abstract Hypoxic-ischemic encephalopathy (HIE) is a diffuse brain tissue injury caused by acute ischemia and hypoxia, and it is most commonly found in newborn infants but can also occur in adults. Mesenchymal stem cell (MSC) therapies have showed improved outcomes for treating HIE-induced neuronal defects. However, many key issues associated with poor cell viability and tolerance of grafted MSCs after HIE remain to be resolved. Genetic engineering could endow MSCs with more robust regenerative capacities. Our research, along with that of other scientists, has found that the expression of intracellular erythropoietin (EPO) in human umbilical cord MSCs (hUC-MSCs) increases proportionally with the duration of hypoxia exposure. Furthermore, we observed that EPO, when introduced into the EPO gene-modified hUC-MSCs, can be secreted into the extracellular space. However, the underlying mechanisms that support the neuroprotective effects of EPO-MSCs remain unclear. EPO-MSCs, hUC-MSCs, and NC-MSCs were identified by flow cytometry, osteogenic, and adipogenic differentiation assays. The oxygen-glucose deprivation (OGD)-induced SH-SY5Y cell-line was established, and five groups were set up: control, 24-h ischemia-hypoxia, co-cultured with hUC-MSCs, NC-MSCs, and EPO-MSCs after hypoxia. LEGENDplex™ multi-factor flow cytometry was used to detect the secretion of inflammatory factors in cell supernatants and cerebrospinal fluid. Chromosome-targeted excision and tagging (CUT&Tag) sequencing was applied to detect genomic H3K4me2 modifications, and conjoint analysis with transcriptome sequencing (RNA-seq) was performed. Lentiviral vector infection was used to construct SH-SY5Y cells with stable knockdown of RE1-silencing transcription factor (REST), and flow cytometry was used to detect alterations in apoptosis. Finally, the molecular mechanism underlying the neuroprotective and anti-apoptotic effects of EPO-MSCs was investigated using RNA sequencing, qRT-PCR, and western blot assays. Our results suggest that EPO-MSCs are genetically engineered to secrete significantly more EPO. EPO-MSCs treatment has anti-apoptotic properties and offers neuronal protection during ischemic-hypoxic injury. Furthermore, RNA-seq results suggest that multiple inflammation-related genes were down-regulated after EPO-MSCs treatment. Application of RNA-seq and CUT&Tag combined analysis found that the expressions of REST were significantly up-regulated. Lentiviral vector infection to construct REST knockdown SH-SY5Y failed to rescue apoptosis after hypoxia and co-culture with EPO-MSCs, and SETD2-mediated H3K36me3 protein level expression was reduced. EPO-MSCs may promote neuronal survival by affecting H3K4me2 and thus activating the expression of REST and TET3. EPO-MSCs also upregulated the modification level of SETD2-mediated H3K36me3 and regulated the expression of inflammation-related genes such as PLCG2, as well as apoptosis genes BCL2A1. To investigate the neuroprotective effects of EPO-modified hUC-MSCs and the underlying epigenetic regulatory mechanisms, this study aims to provide a theoretical foundation for the potential application of EPO gene-modified hUC-MSCs in the treatment of HIE.

Cultural relics visualization brings digital archives of relics to broader audiences in many applications, such as education, historical research, and virtual museums. However, previous research mainly focused on modeling and rendering the relics. While enhancing accessibility, these techniques still provide limited ability to improve user engagement. In this paper, we introduce RelicCARD, a semantics-based augmented reality (AR) tangible interaction design for exploring cultural relics. Our design uses an easily available tangible interface to encourage the users to interact with a large collection of relics. The tangible interface allows users to explore, select, and arrange relics to form customized scenes. To guide the design of the interface, we formalize a design space by connecting the semantics in relics, the tangible interaction patterns, and the exploration tasks. We realize the design space as a tangible interactive prototype and examine its feasibility and effectiveness using multiple case studies and an expert evaluation. Finally, we discuss the findings in the evaluation and future directions to improve the design and implementation of the interactive design space.

The left ventricular diverticulum (LVD) is a rare congenital heart disease commonly discovered during examinations. Herein, we report a LVD on the lateral wall of left ventricular outflow tract. A case of a 22-year-old female patient who visited our hospital with complaints of shortness of breath, accompanied by vomiting, cough, and lower limb and facial edema and was diagnosed with “aortopulmonary septal defect” using transthoracic echocardiography. After cardiac surgery and postoperative pathology, she was confirmed with a LVD. The patient's clinical symptoms, multimodal imaging examination, and treatment methods were used to assess this case.

Background: Maduramicin (MAD) is an anticoccidial veterinary drug, but it frequently causes fatal poisonings in poultry, livestock, or humans. However, there is no specific antidote or guidance on first aid for MAD poisoning. Aim: The aim of the present study is to evaluate the acute toxicity and toxicokinetics of MAD after oral exposure, so as to make a foundation for developing diagnostic and therapeutic protocols for human intoxication. Methods: Five groups of rats (eight-to-nine-week-old male Wistar rats) were orally administered MAD via gavage at doses of 0, 4.64, 10.0, 21.5, or 46.4 mg/kg bw for only one time. The survival rates of the rats were observed over the following 14 days to assess acute toxicity. To evaluate the toxic effects of MAD, two doses (4.8 mg/kg bw and 10 mg/kg bw) were orally administered via gavage. Biochemical parameters including creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, urea, creatinine, serum myoglobin, and urinary myoglobin were measured. Liver, kidney, heart, and hind limb skeletal muscle samples from severely poisoned rats were obtained for pathological examination. For toxicokinetic analysis, samples of serum, urine, and feces from the 4.8 mg/kg bw dose group were analyzed using high-performance liquid chromatography-tandem mass spectrometry. Results: The LD50 of MAD in male Wistar rats was determined to be 6.81 mg/kg bw. In the 10 mg/kg bw group, elevated serum urea levels and increased myoglobin levels in both serum and urine indicated renal injury and potential muscle damage. Toxicokinetics in serum revealed that following oral administration of 4.8 mg/kg bw MAD, peak serum concentration of 59.8 ± 8.9 μg/L was achieved at 30.0 ± 13.9 h. MAD exhibited a slow elimination from the blood with an elimination half-life of 72.9 ± 36.8 h and a mean residence time of 79.6 ± 25.5 h. Additionally, fecal excretion of MAD was found to be greater than urinary excretion. Conclusion: MAD is a highly toxic veterinary drug which requires careful handling. The primary effects of poisoning include kidney injury and suspected rhabdomyolysis. It is excreted very slowly after oral administration. Promoting toxin excretion in individuals poisoned by MAD could potentially serve as an effective treatment method until a specific antidote is identified.

Objectives: This study aimed to analyze each myocardial segment's ischemic burden, scarring, function, and viability by late gadolinium enhancement (LGE) imaging and stress-MRI using adenosine. Materials and methods: Semi-quantitative and qualitative parameters of myocardial segments were obtained by stress-MRI. Moreover, segments without perfusion defect were defined as the no ischemic group, segments with a perfusion defect of ≤50% were defined as a low ischemic burden group, and segments with a perfusion defect of >50% were defined as a high ischemic burden group. “Segmental wall thickening (SWT)” was defined as the absolute difference between the end-diastolic and end-systolic wall thickness. Finally, viability was defined by dysfunctional myocardium (50%. Among the different ischemic burden groups, there were significant differences in LGE volume (p ​ ​0.05). Conclusions: Stress MRI parameters can accurately and detailly assess myocardial viability and function, so multi-parameter joint assessment of CTO patients by stress MRI may help in treatment decisions.

Non-typhoidal Salmonella enterica (NTS) is a major global foodborne pathogen that poses a major public health concern worldwide, and no vaccines are available for protecting against infection of multiple Salmonella serotypes, therefore, the development of Salmonella vaccines to provide broad protection is valuable. In this work, we aimed to regulate lipopolysaccharide (LPS) synthesis of live Salmonella in vivo for exposing conserved protein antigens on the outer membrane while maintaining smooth LPS patterns in vitro to keep their original ability to invade host cells for inducing cross-protection against infection of multiple Salmonella serotypes. We generated a series of mutants defective in genes to affect the length of LPS. These mutants exhibit in vivo regulated-delayed attenuation and altered length of LPS, and all these mutants were derived from SW067 (ΔpagL7 ΔpagP81::Plpp lpxE ΔlpxR9 Δfur9) containing ∆pagP81::Plpp lpxE mutation to reduce their endotoxic activity. Animal experiments demonstrated that all regulated delayed attenuated mutants exhibited reduced ability to colonize the organs of the mice, and SW114 (waaI), SW116 (waaJ), SW118 (waaL), and SW120 (wbaP) induced a significant production of IgG and IgA against OMPs isolated from S. Typhimurium, S. Enteritidis, and S. Choleraesuis. SW114 (waaI), SW116 (waaJ), and SW118 (waaL) were capable of conferring significant protection against infection of wild-type S. Enteritidis and S. Choleraesuis, with SW118 (waaL) triggering significant CD4+ T-cell responses as well as the B220low IgG+ BM cell. In conclusion, regulated delayed attenuated Salmonella vaccines with the whole core oligosaccharides of LPS showed a goo.d ability to expose conserved outer antigens and to trigger strong cross-immune responses against both homologous and heterologous Salmonella infections. These results give new insight into the development of the Salmonella vaccine against multiple serotypes of Salmonella.

BackgroundLaparoscopic total gastrectomy plus lymph node dissection is an effective treatment method for patients with gastric cancer. With the development and popularization of laparoscopic techniques in recent years, surgeons have become more skilled in laparoscopic techniques. Totally laparoscopic total gastrectomy (TLTG) has been developed; however, digestive tract reconstruction remains difficult, especially with anastomosis of the esophagus and jejunum. Using the self-pulling and latter transection (SPLT) method combined with a linear stapler has effectively solved the problem of narrow space in esophagojejunostomy. Here, we examined the safety and effectiveness of the SPLT technique in TLTG compared with SPLT with traditional esophagojejunostomy overlap anastomosis.MethodsWe retrospectively analyzed all patients with gastric cancer admitted to the Department of Gastrointestinal Surgery of the Second Affiliated Hospital of Fujian Medical University from September 2020 to September 2023. In total, 158 patients met the inclusion criteria and were included. Patients were grouped according to whether the lower esophagus was transected after self-pulling. Patient demographics, tumor characteristics, surgical conditions, and postoperative results between the two groups were statistically analyzed.ResultsA total of 158 patients were included in the study. All patients underwent TLTG and completed intracavitary anastomosis. There were 70 cases (44%) in the SPLT-Overlap group and 88 cases (56%) in the traditional overlap group. There was no significant difference in demographic and oncological characteristics between the two groups. The operation time (P = 0.002) and esophageal jejunum anastomosis time (P

Janus monolayers of transition metal dichalcogenides (TMDCs) are promising building blocks for moiré superlattices because of their built‐in electric field and clean fabrication process. In particular, Janus TMDC monolayers can be chemically converted from conventional TMDC monolayers by atomic substitution, enabling the direct formation of lattice‐mismatched heterobilayers from TMDC bilayers. However, the moiré superlattices of Janus heterobilayers have not been studied experimentally. Herein, this work reports the fabrication and characterization of semiconductor moiré superlattices in chemically tailored Janus heterobilayers. The MoSSe/MoSe2 (or WSSe/WSe2) Janus heterobilayers are prepared by replacing the top layer Se atoms with S atoms in MoSe2 (or WSe2) bilayer using H2 plasma treatment. Scanning transmission electron microscopy reveals that an average moiré period of about 14 nm formed due to lattice mismatch resulting from the chalcogen substitutions. The cryogenic photoluminescence spectra show sharp, near‐infrared emissions, which are attributed to excitons trapped by moiré potentials based on comparison with theoretical calculations. The Janus‐based heterostructures provide a long‐period moiré system with built‐in potential even for nontwisted heterobilayers, allowing the functionalization of confined and correlated electron systems.

This study conducted a comparison of the effects of non-protein nitrogen with different acid-base properties on feed intake, rumen fermentation, nutrient digestion and antioxidant capacity in fattening Hu sheep. Sixteen fattening male sheep (31.43 ± 2.41 kg) with permanent rumen cannulas were randomly assigned to two dietary treatments: 1% urea and 1.78% ammonium chloride (NH4Cl, AC). A 42 days experimental period was conducted, with 14 days for adaptation and 28 days for treatment. Daily feed intake was recorded and various samples including feed, feces, rumen fluid, and blood were collected at different time points during the final week. The results indicated that the urea group had significantly higher dry matter intake, average daily gain, and gain efficiency in comparison to the AC group (p 0.05), but the rumen pH of urea group was higher than that of the AC group at 1 and 3 h after feeding (p

The fracture structure is complex and irregular, which has a decisive influence on the migration and storage of pressure-relief gas in overlying strata. During the advancing process of the fully mechanized mining face in the high-gas thick-coal seam, in order to determine the impact of dynamic change of intersection and fusion of the gas transport and storage area on the gas occurrence, and the gas transport and storage law in the overlying strata under different advancing speeds, the two-dimensional physical similarity simulation was conducted to analyze the fracture distribution characteristics of the overlying strata and the geometric change law of the gas transport-storage area, and explore the change characteristics of the gas transport-storage area with the periodic weighting under different advancing speeds. Additionally, taking the advancing speed of the working face as a key parameter, the quantitative characterization model of the propulsion speed effect of the gas transport-storage area was established, and the symmetrical periodic construction mechanism of the gas transport-storage area under the influence of the advancing speed was revealed. The results show that the inner and outer boundaries and the boundary between the gas transport area and storage area are located in the mutation areas of the fracture openness and through degree respectively. With the increase of the advancing speed, the boundary of the transport-storage area is reduced from the middle of the goaf to both sides. As the working face advances, the gas storage area gradually transits into a migration area, and the two areas cross and fuse with each other. During the whole process, the transport-storage area is in the cycle of “construction-destruction-construction”, and finally form a complete symmetrical elliptical parabolic banded overburden fracture field. The change of fracture entropy increases first and then decreases with the advance of the working face, and the change of fracture rate increases and decreases twice with the advance of the working face respectively, indicating that the gas migration area and the storage area show the dynamic change of “initial formation-cross fusion-regional separation and expansion” with the advance of the working face. In addition, based on the theory of mining-induced fracture elliptic paraboloid zone, the quantitative characterization model of propulsion speed effect of gas transport-storage zone was constructed, and the boundary and state determination process of gas transport-storage zone was established. The cross-fusion evolution mechanism and symmetric periodic construction mechanism of gas transport-storage area under the influence of advancing speed were revealed, which provide a guidance for studying the distribution of pressure-relief gas in goaf and realizing the directional and accurate extraction of gas enrichment zone.

Abstract Introduction The cannabinoid receptor 2 (CB2) is mainly involved in the immune system. However, although CB2 has been reported to play an anti‐tumor function in breast cancer (BC), its specific mechanism in BC remains unclear. Methods We examined the expression and prognostic significance of CB2 in BC tissues by qPCR, second‐generation sequencing, western blot, and immunohistochemistry. We assessed the impacts of overexpression and a specific agonist of CB2 on the growth, proliferation, apoptosis, and drug resistance of BC cells in vitro and in vivo using CCK‐8, flow cytometry, TUNEL staining, immunofluorescence, tumor xenografts, western blot, and colony formation assays. Results CB2 expression was significantly lower in BC compared with paracancerous tissues. It was also highly expressed in benign tumors and ductal carcinoma in situ, and its expression was correlated with prognosis in BC patients. CB2 overexpression and treatment of BC cells with a CB2 agonist inhibited proliferation and promoted apoptosis, and these actions were achieved by suppressing the PI3K/Akt/mTOR signaling pathway. Moreover, CB2 expression was increased in MDA‐MB‐231 cell treated with cisplatin, doxorubicin, and docetaxel, and sensitivity to these anti‐tumor drugs was increased in BC cells overexpressing CB2. Conclusions These findings reveal that CB2 mediates BC via the PI3K/Akt/mTOR signaling pathway. CB2 could be a novel target for the diagnosis and treatment of BC.

To reduce financial pressure and operational risk, and improve match between supply and demand, an increasing number of enterprises are adopting presales to launch new products. In this context, this paper investigates three presale models for innovative products, namely, the no-presale model, the manufacturer presale model and the retailer presale model. A Hotelling model is used to describe the impact of channel preferences and valuation differences on the two-stage competition between innovative products. Aiming at evaluating the purchase behavior of consumers under three presale modes, a game optimization model is established to analyze the presale decision problem for innovative products under different presale entities. The research shows that: (1) Compared with no-presale, presales can help enterprises obtain more profits. The overall profit of the supply chain is optimal under the retailer presale mode. (2) When the difference in channel preferences is small, the manufacturer obtains the greatest profit by choosing the direct presale model. In contrast, the selection of different presale entities has a significant impact on product sales and supply chain enterprise profits. At this point, the manufacturer should choose the retailer presale model. (3) When the product valuation discount is high, the manufacturer can increase the spot and wholesale prices to induce consumers to choose the presale method to purchase the product. In the opposite situation, the manufacturer should lower the presale price to improve the presale utility of consumers and encourage them to participate in the presale. These conclusions provide more targeted suggestions for enterprises to formulate presale strategies, which can help them grasp market demand and improve market competitiveness.

Wind and solar energy are the important renewable energy sources, while their inherent natures of random and intermittent also exert negative effect on the electrical grid connection. As one of multiple energy complementary route by adopting the electrolysis technology, the wind-solar-hydrogen hybrid system contributes to improving green power utilization and reducing its fluctuation. Therefore, the moving average method and the hybrid energy storage module are proposed, which can smooth the wind-solar power generation and enhance the system energy management. Moreover, the optimization of system capacity configuration and the sensitive analysis are implemented by the MATLAB program platform. The results indicate that the 10-min grid-connected volatility is reduced by 38.7% based on the smoothing strategy, and the internal investment return rate can reach 13.67% when the electricity price is 0.04 $/kWh. In addition, the annual coordinated power and cycle proportion of the hybrid energy storage module are 80.5% and 90%, respectively. The developed hybrid energy storage module can well meet the annual coordination requirements, and has lower levelized cost of electricity. This method provides reasonable reference for designing and optimizing the wind-solar-hydrogen complementary system.

Modern insecticide substitutes using acetylcholine receptors (nAChR) as biochemical targets, such as neonicotinoid insecticides (NNIs), have been extensively researched. Only 12 compounds have been experimentally realized since the initial discovery of imidacloprid. Increasingly, the bottleneck in this field is to rapidly determine the synthesizability of NNI substitutes. Here, we designed a coupled evaluation system for synthesis prediction and validation, including the synthesis probability, reaction path difficulty, and electron transfer characteristics of NNIs and their substitutes. Firstly, a total of 1475 eigenvalues were generated and 52 critical eigenvalues were screened out through the Pearson’s correlation coefficient. The positive and unlabeled (PU) machine learning was constructed using the critical eigenvalues NNIs, including 12 experimentally synthesized NNIs (positive samples) and 73 unsynthesized NNI substitutes (unlabeled samples). Results identified 3 NNI substitutes that were highly promising candidates for synthesis (synthesis probability > 0.5). The results of density functional theory demonstrated the ranking of their reaction ease was UN-1 (31.4 kcal/mol) > UN-2 (81.6 kcal/mol) > UN-3 (3.35 ×103 kcal/mol). Time-dependent density functional theory revealed that changes in the electron distribution and electron excitation type were critical factors affecting their synthesizability, and the local excitation type was more favorable for the synthesizability of NNI substituents. The findings provide significant guidance for NNIs synthesis, reducing the possible space of unlabeled samples to 95.89% of their original size, while also minimizing the cost of research on subsequent NNI substitutes.

All-inorganic metal halide perovskite is promising for highly efficient and thermally stable perovskite light-emitting diodes (PeLEDs). However, there is still great room for improvement in the film quality, including low coverage and high trap density, which play a vital role in achieving high-efficiency PeLEDs. In this work, lead acetate (Pb(Ac)2) was introduced into the perovskite precursor solution as an additive. Experimental results show that perovskite films deposited from a one-step anti-solvent free solution process with increased surface coverage and reduced trap density were obtained, leading to enhanced photoluminescence (PL) intensity. More than that, the valence band maximum (VBM) of perovskite films was reduced, bringing about a better energy level matching the work function of the hole-injection layer (HIL) poly (3,4-ethylenedioxythiophene)-poly (styrene sulfonate) (PEDOT: PSS), which is facilitated for the hole injection, leading to a decrease in the turn-on voltage (Vth) of PeLEDs from 3.4 V for the control device to 2.6 V. Finally, the external quantum efficiency (EQE) of the sky blue PeLEDs (at 484 nm) increased from 0.09% to 0.66%. The principles of Pb(Ac)2 were thoroughly investigated by using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). This work provides a simple and effective strategy for improving the morphology of perovskite and therefore the performance of PeLEDs.

Rhizoma atractylodis, including Atractylodes lancea and Atractylodes chinensis, is widely utilized worldwide as a Chinese meteria medica (CMM) due to its rich content of various sesquiterpenoids and other medicinal components. Benefiting from the rapid and ongoing advancements in analytical technologies, significant strides have been achieved in advancing the analysis of Rhizoma atractylodis towards a more systematic, comprehensive, personalized, and intelligent approach. In this review, we highlight the progress made in the biogeography, biosynthesis, quality formation, and control of Rhizoma atractylodis over the past decade. Special attention is given to the incorporation of advanced genetics tools, modern omics technology, and chemometric methods that facilitate the accurate utilization of Rhizoma atractylodis. The elucidation of biosynthetic pathways, the formation of quality, and the control of active components continue to pose challenges in the study of Rhizoma atractylodis. Additionally, this review presents novel directions and opportunities aimed at enhancing ongoing research efforts.

Macrolides are currently a class of extensively used antibiotics in human and animal medicine. Tylosin is not only one of the most important veterinary macrolides but also an indispensable material for the bio- and chemo-synthesis of new generations of macrolide antibiotics. Thus, improving its production yield is of great value. As the key rate-limiting enzyme catalyzing the terminal step of tylosin biosynthesis in Streptomyces fradiae (S. fradiae), TylF methyltransferase’s catalytic activity directly affects tylosin yield. In this study, a tylF mutant library of S. fradiae SF-3 was constructed based on error-prone PCR technology. After two steps of screening in 24-well plates and conical flask fermentation and enzyme activity assay, a mutant strain was identified with higher TylF activity and tylosin yield. The mutation of tyrosine to phenylalanine is localized at the 139th amino acid residue on TylF (TylFY139F), and protein structure simulations demonstrated that this mutation changed the protein structure of TylF. Compared with wild-type protein TylF, TylFY139F exhibited higher enzymatic activity and thermostability. More importantly, the Y139 residue in TylF is a previously unidentified position required for TylF activity and tylosin production in S. fradiae, indicating the further potential to engineer the enzyme. These findings provide helpful information for the directed molecular evolution of this important enzyme and the genetic modification of tylosin-producing bacteria.

A gas chromatography method was established to simultaneously detect 26 kinds of organophosphorus pesticide residuesin wheat germ samples, such as dichlorvos, ethoprophos, and cadusafos. By optimizing the pretreating procedures of samples and test conditions of gas chromatography, the target organophosphorus pesticide residues were separated by DB-17 capillary column and temperature programming, and corresponding amounts were detected using flame photometric detector (FPD). The results showed that the concentrations of all organophosphorus pesticide residues were linearly related to their peak areas with correlation coefficients of over 0.999 in the concentration 0.010~1.0 μg/mL, and the minimum quantitative concentrations of all organophosphorus pesticide residues were between 0.005 and 0.010 mg/kg, respectively. The recoveries of spiked samples at 3 levels ranged from 80.61% to 116.19% with relative standard deviations between 0.62%~6.83%. This method had been successfully applied in qualitative screening and quantitative detection of 26 kinds of organophosphorus pesticide residues in wheat germ samples. Alathion, chlorpyrifos-methyl and fenitrothion were detected in actual samples, and the contents of positive organophosphorus pesticides were 0.074±0.005, 0.062±0.004, 0.043±0.002 mg/kg.

Green hydrogen generation driven by solar-wind hybrid power is a key strategy for obtaining the low-carbon energy, while by considering the fluctuation natures of solar-wind energy resource, the system capacity configuration of power generation, hydrogen production and essential storage devices need to be comprehensively optimized. In this work, a solar-wind hybrid green hydrogen production system is developed by combining the hydrogen storage equipment with the power grid, the coordinated operation strategy of solar-wind hybrid hydrogen production is proposed, furthermore, the NSGA-III algorithm is used to optimize the system capacity configuration with the comprehensive performance criteria of economy, environment and energy efficiency. Through the implemented case study with the hydrogen production capacity of 20,000 tons/year, the abandoned energy power rate will be reduced to 3.32% with the electrolytic cell average load factor of 64.77%, and the system achieves the remarkable carbon emission reduction. In addition, with the advantage of connect to the power grid, the generated surplus solar/wind power can be readily transmitted with addition income, when the sale price of produced hydrogen is suggested to 27.80 CNY/kgH2, the internal rate of return of the system reaches to 8% which present the reasonable economic potential. The research provides technical and methodological suggestions and guidance for the development of solar-wind hybrid hydrogen production schemes with favorable comprehensive performance.

ABSTRACT Bacterial morphology is largely determined by the spatial and temporal regulation of peptidoglycan (PG) biosynthesis. Ovococci possess a unique pattern of PG synthesis different from the well studied Bacillus, and the mechanism of the coordination of PG synthesis remains poorly understood. Several regulatory proteins have been identified to be involved in the regulation of ovococcal morphogenesis, among which DivIVA is an important one to regulate PG synthesis in streptococci, while its mechanism is largely unknown. Here, the zoonotic pathogen Streptococcus suis was used to investigate the regulation of DivIVA on PG synthesis. Fluorescent d-amino acid probing and 3D-structured illumination microscopy found that DivIVA deletion caused abortive peripheral PG synthesis, resulting in a decreased aspect ratio. The phosphorylation-depleted mutant (DivIVA3A) cells displayed a longer nascent PG and became longer, whereas the phosphorylation-mimicking mutant (DivIVA3E) cells showed a shorter nascent PG and became shorter, suggesting that DivIVA phosphorylation is involved in regulating peripheral PG synthesis. Several DivIVA-interacting proteins were identified, and the interaction was confirmed between DivIVA and MltG, a cell wall hydrolase essential for cell elongation. DivIVA did not affect the PG hydrolysis activity of MltG, while the phosphorylation state of DivIVA affected its interaction with MltG. MltG was mislocalized in the ΔdivIVA and DivIVA3E cells, and both ΔmltG and DivIVA3E cells formed significantly rounder cells, indicating an important role of DivIVA phosphorylation in regulating PG synthesis through MltG. These findings highlight the regulatory mechanism of PG synthesis and morphogenesis of ovococci. IMPORTANCE The peptidoglycan (PG) biosynthesis pathway provides a rich source of novel antimicrobial drug targets. However, bacterial PG synthesis and its regulation is a very complex process involving dozens of proteins. Moreover, unlike the well studied Bacillus, ovococci undergo unusual PG synthesis with unique mechanisms of coordination. DivIVA is an important regulator of PG synthesis in ovococci, while its exact role in regulating PG synthesis remains poorly understood. In this study, we determined the role of DivIVA in regulating lateral PG synthesis of Streptococcus suis and identified a critical interacting partner, MltG, in which DivIVA influenced the subcellular localizations of MltG through its phosphorylation. Our study characterizes the detailed role of DivIVA in regulating bacterial PG synthesis, which is very helpful for understanding the process of PG synthesis in streptococci.

With the global climate problem becoming increasingly severe, governments have adopted policies to encourage enterprises to invest in low-carbon technologies. However, the opacity of the carbon emission reduction process leads to incomplete consumer trust in low-carbon products as well as higher supply chain transaction costs. Based on this, this paper constructs Stackelberg game models with and without blockchain under different power structures and compares the impact of these models on low-carbon emission reduction decisions. The results show that: (1) blockchain does not necessarily improve enterprise profits and can only help enterprises maintain optimal profits within a certain range when the carbon emission cost is low; (2) when consumers’ environmental awareness is high, the blockchain can incentivize manufacturers to enhance carbon emission reduction, and it has an obvious promotional effect on retailers’ profits; and (3) the profit gap between enterprises in the supply chain is larger under different power structures, and the implementation of blockchain can coordinate profit distribution and narrow the gap between enterprises. Compared with the manufacturer-dominated model, the emission reduction in products is maximized under the retailer-dominated model. Our study provides theoretical support for the government to regulate greenhouse gas emissions as well as for the optimization of enterprises’ decision-making supported by blockchain.

Moiré materials provide fertile ground for the correlated and topological quantum phenomena. Among them, the quantum anomalous Hall (QAH) effect, in which the Hall resistance is quantized even under zero magnetic field, is a direct manifestation of the intrinsic topological properties of a material and an appealing attribute for low-power electronics applications. The QAH effect has been observed in both graphene and transition metal dichalcogenide (TMD) moiré materials. It is thought to arise from the interaction-driven valley polarization of the narrow moiré bands. Here, we show that the newly discovered QAH state in AB-stacked MoTe_{2}/WSe_{2} moiré bilayers is not valley polarized but valley coherent. The layer- and helicity-resolved optical spectroscopy measurement reveals that the QAH ground state possesses spontaneous spin (valley) polarization aligned (antialigned) in two TMD layers. In addition, saturation of the out-of-plane spin polarization in both layers occurs only under high magnetic fields, supporting a canted spin texture. Our results call for a new mechanism for the QAH effect and highlight the potential of TMD moiré materials with strong electronic correlations and spin-orbit interactions for exotic topological states.

Surface-enhanced Raman scattering (SERS) has garnered substantial attention due to its ability to achieve single-molecule sensitivity by utilizing metallic nanostructures to amplify the exceedingly weak Raman scattering process. However, the introduction of metal nanostructures can induce a background continuum which can reduce the ultimate sensitivity of SERS in ways that are not yet well understood. Here, we investigate the impact of laser irradiation on both Raman scattering and backgrounds from self-assembled monolayers within nanoparticle-on-mirror plasmonic nanocavities with variable geometry. We find that laser irradiation can reduce the height of the monolayer by inducing an irreversible change in molecular conformation. The resulting increased plasmon confinement in the nanocavities not only enhances the SERS signal, but also provides momentum conservation in the inelastic light scattering of electrons, contributing to the enhancement of the background continuum. The plasmon confinement can be modified by changing the size and the geometry of nanoparticles, resulting in a nanoparticle geometry-dependent background continuum in SERS. Our work provides new routes for further modifying the geometry of plasmonic nanostructures to improve SERS sensitivity.

The isolated single vacancy is one of the most common defects in diamond, while it is of considerable interest and importance that significantly influences the optical properties of diamond. Although a number of literature publications about the electron structure and density states of single vacancy in diamond from the density functional theory (DFT) calculations, these results are very difficult to be identified from the perspective of experiments. In this paper, the low-temperature photoluminescence (PL) technology was employed to study the emission properties of single vacancy in diamond, and then the photoionization energy, migration energy and vibrionic structure obtained from PL experiments were compared with these obtained from the first-principle calculations. Results showed that the calculation results agreed well with the PL results for the neutral vacancy while differed for the negatively charged vacancy, indicating that for ultrapure diamond, the vacancy mainly existed in form of the neutral rather than the negatively charged.

Abstract Temporary consolidation is a quite common practice during archeological excavations nowadays. Melts of cyclododecane or menthol are among the most used consolidants. When using melting protocol to consolidate fragile heritages in archaeological excavation sites, one of the most frequently encountered challenges is the poor penetration of the melt into the heritages, especially in cases of low environmental temperatures, high water content or compact substrates. In this work, we explore the possibility of using solvent-assisted menthol sols as temporary consolidant. Six common organic liquids are individually introduced into menthol at a concentration of 9.1 wt% to formulate room temperature menthol sols. Their potentials as temporary consolidants are systematically investigated. Experimental data indicate that solvent polarity is the most important feature for temporary consolidation purpose and ethanol with medium polarity is among the most appropriate solvents. Laboratory research results show that much better penetration behavior and good consolidation performances can be achieved in menthol-ethanol sol. The as-prepared menthol-ethanol sol is applied in Liangzhu archeological excavation site with satisfactory outcomes. This work shows that menthol-ethanol sol is an excellent temporary consolidation material for archaeological excavation purpose especially in extremely wet condition.

In the context of developing the digital platform economy, trade-in programs have become an effective strategy for e-commerce platforms to stimulate consumption. Many head e-commerce platforms have launched their own trade-in programs. However, the existing research on trade-in programs is still stuck in the traditional trade-in model. The purpose of this study is to explore whether there is a new and more beneficial trade-in program. In this paper, we construct the Stackelberg game model between a brand owner and a B2C e-commerce platform under two trade-in programs and use optimization theory to obtain the equilibrium results of the model. The results indicate that the performance improvement of the new-generation product will promote the increase in two-generation products’ price under traditional trade-in programs, the price of the new-generation product will increase, and the price of the previous-generation product will decrease under new trade-in programs. The brand owner always prefers traditional trade-in to new trade-in. However, the e-commerce platform prefers traditional trade-in to new trade-in just when the previous-generation product is durable enough and the performance improvement of a new-generation product is small enough; otherwise, it prefers new trade-in to traditional trade-in. These findings are beneficial to the operational practices of e-commerce platforms and brand owners.

PurposeTo provide preliminary data on the efficacy and safety of oral voriconazole (VCZ) as a primary treatment for fungal keratitis (FK).MethodWe performed a retrospective histopathological analysis of data on 90 patients with FK at The First Affiliated Hospital of Guangxi Medical University between September 2018 and February 2022. We recorded three outcomes: corneal epithelial healing, visual acuity (VA) improvement, and corneal perforation. Independent predictors were identified using univariate analysis, and multivariate logistic regression analysis was used to identify independent predictive factors associated with the three outcomes. The area under the curve was used to evaluate the predictive value of these factors.ResultsNinety patients were treated with VCZ tablets as the only antifungal drug. Overall, 71.1% (n = 64) of the patients had extreme corneal epithelial healing, 56.7% (n = 51) showed an improvement in VA, and 14.4% (n = 13) developed perforation during treatment. Non-cured patients were more likely to have large ulcers (≥5 × 5 mm2) and hypopyon.ConclusionThe results indicated that oral VCZ monotherapy was successful in the patients with FK in our study. Patients with ulcers larger than 5 × 5 mm2 and hypopyon were less likely to respond to this treatment.

Effective method of bilateral matching decision-making could drive the property transaction market more dynamic and healthier. In the property trade process, once intermediaries are conscientious, the portrait of matching parties are clearly described, a reasonable and satisfactory result can be got. However, the intermediary moral hazard and the loss of the description about the characteristics of matching parties can affect the matching result. By developing a method for a property transaction platform, this paper proposes a novel approach that considering intermediary moral hazard to improve matching efficiency. A mathematical model of intermediary moral hazard is performed, and then the price and other evaluation indicators of sellers and buyers are described by five different types of value forms. A multi-objective bilateral matching decision-making model that “minimizes the intermediary moral hazard in the case of the maximum benefits of the matching parties” is constructed and solved by the dictionary order method. A real case study of property trade platform is presented to illustrate how the proposed approach could be applied in practice. The results of this research indicate that the proposed approach is a useful tool for matching sellers and buyers under the intermediary moral hazard and has substantial practical application.

BackgroundOne of the milestones in bacterial-mediated therapy for cancer, Bacillus Calmette-Guerin (BCG) has been used to treat bladder cancer (BC) for more than 30 years. BCG immunotherapy is now the standard of care for high-grade non-muscle invasive bladder cancer (NMIBC) following transurethral resection.MethodsWe searched the Web of Science core collection (WoSCC) database and used bibliometric methods through CiteSpace (version 5.1.R6), VOSviewer (version 1.6.18) and R-Bibliometrix (version R 4.2.1) to analyze and discuss the current status and trends of BCG therapy of BC from 2012 to 2021 in terms of co-occurrence, co-polymerization and visualization.ResultsA total of 2476 publications were found, with the majority coming from the United States and China. Over the last decade, overall yearly outputs have increased fivefold, from 117 papers in 2012 to 534 records in 2021. Most publications were produced by the University of Texas System. The authors, Ashish M. Kamat of the University of Texas-MD Anderson Cancer Center in the United States, and Shahrokh F. Shariat of Weill Cornell Medical College, were pioneers in this field with the most publications. The journals, Urologic Oncology Seminars and Original Investigations, Cancers and Frontiers in Oncology, have published a dramatic increase in the number of articles, and tumor and urology nephrology research directions have received the most attention from journals. Furthermore, recent research has concentrated on muscle-invasive bladder cancer (MIBC). BCG therapy mechanism, BCG dose and strains, targeted therapy and immune checkpoint inhibitors (ICIs) for BC were attractive research contents, with ICIs (PD-1, PD-L1) being the most popular study point in recent years. With more research on tumor immunology, screening for more reliable biomarkers for precision treatment, and the development of combination regimens of ICIs, targeted treatment of BC stem cells, and personalized BC therapies may be promising areas of immunotherapy research in the coming years.ConclusionThe results of this bibliometric study can provide the current status and research trends of BCG therapy for BC in the last decade, and also further complements the research content of bacterial-mediated cancer therapy.

Cancer, the second largest human disease, has become a major public health problem. The prediction of chemicals’ carcinogenicity before their synthesis is crucial. In this paper, seven machine learning algorithms (i.e., Random Forest (RF), Logistic Regression (LR), Support Vector Machines (SVM), Complement Naive Bayes (CNB), K-Nearest Neighbor (KNN), XGBoost, and Multilayer Perceptron (MLP)) were used to construct the carcinogenicity triple classification prediction (TCP) model (i.e., 1A, 1B, Category 2). A total of 1444 descriptors of 118 hazardous organic chemicals were calculated by Discovery Studio 2020, Sybyl X-2.0 and PaDEL-Descriptor software. The constructed carcinogenicity TCP model was evaluated through five model evaluation indicators (i.e., Accuracy, Precision, Recall, F1 Score and AUC). The model evaluation results show that Accuracy, Precision, Recall, F1 Score and AUC evaluation indicators meet requirements (greater than 0.6). The accuracy of RF, LR, XGBoost, and MLP models for predicting carcinogenicity of Category 2 is 91.67%, 79.17%, 100%, and 100%, respectively. In addition, the constructed machine learning model in this study has potential for error correction. Taking XGBoost model as an example, the predicted carcinogenicity level of 1,2,3-Trichloropropane (96−18−4) is Category 2, but the actual carcinogenicity level is 1B. But the difference between Category 2 and 1B is only 0.004, indicating that the XGBoost is one optimum model of the seven constructed machine learning models. Besides, results showed that functional groups like chlorine and benzene ring might influence the prediction of carcinogenic classification. Therefore, considering functional group characteristics of chemicals before constructing the carcinogenicity prediction model of organic chemicals is recommended. The predicted carcinogenicity of the organic chemicals using the optimum machine leaning model (i.e., XGBoost) was also evaluated and verified by the toxicokinetics. The RF and XGBoost TCP models constructed in this paper can be used for carcinogenicity detection before synthesizing new organic substances. It also provides technical support for the subsequent management of organic chemicals.

Ammonia is an important rumen internal environment indicator. In livestock production, feeding a large amount of non-protein nitrogen to ruminants will create high ammonia stress to the animals, which increases the risk of ammonia toxicity. However, the effects of ammonia toxicity on rumen microbiota and fermentation are still unknown. In this study, an in vitro rumen fermentation technique was used to investigate the effects of different concentrations of ammonia on rumen microbiota and fermentation. To achieve the four final total ammonia nitrogen (TAN) concentrations of 0, 8, 32, and 128 mmol/L, ammonium chloride (NH4Cl) was added at 0, 42.8, 171.2, and 686.8 mg/100 mL, and urea was added at 0, 24, 96, and 384 mg/100 mL. Urea hydrolysis increased, while NH4Cl dissociation slightly reduced the pH. At similar concentrations of TAN, the increased pH of the rumen culture by urea addition resulted in a much higher free ammonia nitrogen (FAN) concentration compared to NH4Cl addition. Pearson correlation analysis revealed a strong negative correlation between FAN and microbial populations (total bacteria, protozoa, fungi, and methanogens) and in vitro rumen fermentation profiles (gas production, dry matter digestibility, total volatile fatty acid, acetate, propionate, etc.), and a much weaker correlation between TAN and the above indicators. Additionally, bacterial community structure changed differently in response to TAN concentrations. High TAN increased Gram-positive Firmicutes and Actinobacteria but reduced Gram-negative Fibrobacteres and Spirochaetes. The current study demonstrated that the inhibition of in vitro rumen fermentation by high ammonia was pH-dependent and was associated with variations of rumen microbial populations and communities.

Combined treatments were designed based on iron-carbon micro-electrolysis treatment (ICME), physical adsorption (PA) with zeolite (Z) or vermiculite (V) and microalgae cultivation (MC, Chlorella vulgaris) for removing pollutants from swine wastewater (SW): ICME + MC (IM), ICME + Z + MC (IZM) and ICME + V + MC (IVM). Results showed that the minimum total nitrogen (TN) of 43.66 mg L−1, NH4+-N of 1.33 mg−1 and total phosphorus (TP) of 0.14 mg−1 were obtained by IVM, while the minimum chemical oxygen demand (COD) was 105 mg−1 via IM. During the process of combined treatments, ICME contributed most to the removal of TN (84.52% by IZM), TP (97.78% by IVM and IZM) and COD (62.44% by IVM), and maximum NH4+-N removal (55.64%) was obtained by MC procedure in IM process. Vermiculite performed better than zeolite during all the combined treatments. Besides, the maximum cell dry weight (CDW, 0.74 g−1) of C. vulgaris was obtained by IM on day 13. The results provide an efficient integrated method for swine wastewater treatment. HIGHLIGHTS Process combining iron-carbon microelectrolysis, vermiculite adsorption and microalgae cultivation was the most efficient for treatment on TN, NH4+-N, TP removal.; Iron carbon micro-electrolysis combined with microalgae cultivation was the most efficient treatment for COD removal.; The maximum biomass harvest was observed on day 13 via combined iron-carbon microelectrolysis and microalgae cultivation.;

In order to study the volatile composition of onion, the volatile flavoring substances of the onion were extracted by headspace solid phase microextraction and determined by gas chromatography-mass spectrometry. The effects of extraction fiber head, extraction temperature, extraction time and desorption time on the total peak area and the number of effective compounds were investigated. The optimum extraction conditions were determined as follows: Extraction fiber 50/30 μm DVB/CAR/PDMS, extraction temperature 60 ℃, extraction time 60 min and desorption time 5 min. Under the optimum experimental conditions, the volatile compounds of onion with three different colors were analyzed and identified. The results showed that a total of 61 kinds of volatile flavor compounds were identified. A total of 37, 40 and 49 volatile flavor compounds were detected in the white, red, and yellow onions, respectively, and the peak area content of these volatile flavor compounds accounted for 70.29%, 81.92% and 79.03% of the total volatile components, respectively. In the 61 volatile flavor compounds, 27 were sulfur compounds, 13 were aldehydes, 13 were alcohols, 4 were ketones and 4 were others. There were 22 kinds of volatile components in the three color onions, of which sulfur-containing compounds account for a relatively large proportion, especially the relative content of diisopropyl disulfide and (E)-1-propenyl-2-propenyl disulfide. The sum of the volatile components of the three color onions accounted for more than 20%, which contributed a lot to the formation of the characteristic flavor of onions. The relative content of sulfur compounds in red and yellow onions was much higher than that of white onions. The relative content of 2-methyl-2-pentenoaldehyde in red onions was higher than that of white and yellow onions.

With the rapid development of computer networking technology, people pay more and more attention to the role of online reviews in management decision making. The existing methods of online reviews fusion are limited to rational decision-making behavior, which does not accord with the characteristics of evaluators’ behavior characteristics in the real environment. In order to solve the online reviews fusion problem based on bounded rational behavior which is closer to the reality of property service quality evaluation, the multi-index and multi-scale (MIMS) method is extended into the generalized form, the online reviews are quantified by using the adverb structure scaling method, and an online reviews fusion method based on the improved TODIM (an acronym in Portuguese of interactive and multi-criteria decision making) model is proposed. The feasibility and effectiveness of the proposed method are verified by an example analysis of property service quality evaluation. The research results are as follows: the adverb structure scaling method is suitable for a large number of online reviews processing, the proposed method improves the efficiency of online reviews information fusion, and it is feasible and effective to evaluate property service quality based on the bounded rationality of evaluator’s behavior. First published online 14 January 2022

Brain morphometric alterations involve multiple brain regions on progression of the disease in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) and exhibit age-related degenerative changes during the pathological aging. Recent advance in brain morphometry as measured using MRI have leveraged Person-Based Similarity Index (PBSI) approach to assess the extent of within-diagnosis similarity or heterogeneity of brain neuroanatomical profiles between individuals of healthy populations and validate in neuropsychiatric disorders. Brain morphometric changes throughout the lifespan would be invaluable for understanding regional variability of age-related structural degeneration and the substrate of inflammatory demyelinating disease. Here, we aimed to quantify the neuroanatomical profiles with PBSI measures of cortical thickness (CT) and subcortical volumes (SV) in 263 MS, 207 NMOSD, and 338 healthy controls (HC) from six separate central datasets (aged 11–80). We explored the between-group comparisons of PBSI measures, as well as the advancing age and sex effects on PBSI measures. Compared to NMOSD, MS showed a lower extent of within-diagnosis similarity. Significant differences in regional contributions to PBSI score were observed in 29 brain regions between MS and NMOSD (P

Abstract Background Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is the most sensitive technique for evaluating gene expression levels. Choosing appropriate reference genes (RGs) is critical for normalizing and evaluating changes in the expression of target genes. However, uniform and reliable RGs for breast cancer research have not been identified, limiting the value of target gene expression studies. Here, we aimed to identify reliable and accurate RGs for breast cancer tissues and cell lines using the RNA-seq dataset. Methods First, we compiled the transcriptome profiling data from the TCGA database involving 1217 samples to identify novel RGs. Next, ten genes with relatively stable expression levels were chosen as novel candidate RGs, together with six conventional RGs. To determine and validate the optimal RGs we performed qRT-PCR experiments on 87 samples from 11 types of surgically excised breast tumor specimens (n = 66) and seven breast cancer cell lines (n = 21). Five publicly available algorithms (geNorm, NormFinder, ΔCt method, BestKeeper, and ComprFinder) were used to assess the expression stability of each RG across all breast cancer tissues and cell lines. Results Our results show that RG combinations SF1 + TRA2B + THRAP3 and THRAP3 + RHOA + QRICH1 showed stable expression in breast cancer tissues and cell lines, respectively, and that they displayed good interchangeability. We propose that these combinations are optimal triplet RGs for breast cancer research. Conclusions In summary, we identified novel and reliable RG combinations for breast cancer research based on a public RNA-seq dataset. Our results lay a solid foundation for the accurate normalization of qRT-PCR results across different breast cancer tissues and cells.

Glycyrrhiza uralensis Fisch. is often cultivated in arid, semi-arid, and salt-affected regions that suffer from drought stress, which leads to the accumulation of reactive oxygen species (ROS), thus causing oxidative stress. Plant growth-promoting bacteria (PGPB) and silicon (Si) have been widely reported to be beneficial in improving the tolerance of plants to drought stress by maintaining plant ROS homeostasis. Herein, combining physiological, transcriptomic, and metabolomic analyses, we investigated the response of the antioxidant system of G. uralensis seedlings under drought stress to Bacillus pumilus (G5) and/or Si treatment. The results showed that drought stress caused the overproduction of ROS, accompanied by the low efficiency of antioxidants [i.e., superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), the ascorbate (AsA)–glutathione (GSH) pool, total carotenoids, and total flavonoids]. Inversely, supplementation with G5 and/or Si enhanced the antioxidant defense system in drought-stressed G. uralensis seedlings, and the complex regulation of the combination of G5 and Si differed from that of G5 or Si alone. The combination of G5 and Si enhanced the antioxidant enzyme system, accelerated the AsA–GSH cycle, and triggered the carotenoid and flavonoid metabolism, which acted in combination via different pathways to eliminate the excess ROS induced by drought stress, thereby alleviating oxidative stress. These findings provide new insights into the comparative and synergistic roles of PGPB and Si in the antioxidant system of plants exposed to drought and a guide for the application of PGPB combined with Si to modulate the tolerance of plants to stress.

Abstract Background Approximately 20% of MM patients harbor glucocorticoid (GC) resistance and are not responsive to therapeutic effect. Chaperoneheat-shock proteins Hsp90 is needed for ligand docking, The imbalance of Hsp90/GRα (glucocorticoid receptor α) may be an important cause of GC resistance. Recent studies have indicated that EPA could repress cancer cell growth by regulating critical influential factors in progression of cancer, consisting of resistance to drugs, chemosensitivity. The aim of the present study was to test the cytotoxic effects of EPA alone or EPA + Dexamethasone in dexamethasone-resistant MM cell (MM.1R) and investigate whether DHA can induce apoptosis and reverse acquired glucocorticoid resistance in dexamethasone-resistant MM cell (MM.1R). Methods Cell Counting Kit-8 (CCK-8) was used to detect the proliferation of MM.1R cells after treating with EPA alone and EPA combined with DEX. Mitochondrial membrane potential was measured by flow cytometry and GRα and Hsp90 protein expression were assessed by western blot analysis. Results EPA alone was able to inhibit cell proliferation as evidenced by CCK-8 assay and the tumor growth was remarkably suppressed by EPA + Dexamethasone, Cell apoptosis after EPA treatment was obviously observed by Flow cytometry analysis of the mitochondrial membrane potential. Analysis of Hsp90 and GRα proteins in MM.1R cells incubated with EPA revealed down-regulation of Hsp90 and up-regulation of GRα. Accordingly, the Hsp90/GRα ratio was significantly decreased with the increase of EPA concentration. Conclusions EPA might be used as a new effective treatment for reversal of glucocorticoid-resistance in multiple myeloma.

Property service mode innovation is the basic means of property service enterprise management. Discussing the property service mode in terms of transformation and upgrading is of rich research significance, taking Wenzhou Sapphire Property Service Co. LTD. in China (hereafter referred to as “Sapphire Service”) as an example. First, based on the development of property service in China, this paper summarizes the 4E mode of traditional property service, ensuring cleaning, ensuring greening, ensuring maintenance and ensuring security, and analyzes the existing problems. Second, combined with the development needs of the property service industry, this paper proposes the 4R mode of modern property service, realizing quality requirements, realizing pleasure service, realizing social responsibility and realizing green health, and summarizes its basic characteristics. Finally, based on the above modes in the practice at Sapphire Service, some management implications are put forward for the industrial transformation and upgrading requirements.

Background: Lynch syndrome is a genetic disease resulting from mismatch repair gene mutation. Vaccine therapy can enhance the immunogenicity of Lynch syndrome and improve the therapeutic efficacy of immunotherapy. However, there is no approved Lynch syndrome vaccine coming onto the market.Methods: Herein, we used gene knockdown method to construct Lynch syndrome cell model, paving way for us to develop Lynch syndrome tumor lysate vaccine. Then the isograft technique was employed for constructing the tumor-bearing mouse model of Lynch syndrome. And this isograft model was treated with PD-1 monoclonal antibody and tumor vaccine, respectively. Flow cytometry was used for detecting the proportion of immune cells and immunosuppressive cells, and ELISA was used for detecting the contents of chemokines and cytokines in the blood circulation system and tumor tissues of mice. Finally, IHC was used to detect the effects of tumor vaccines as well as PD-1 antibody on tumor tissue proliferation and angiogenesis.Results: The results demonstrated that tumor vaccine could prolong the overall survival of mice, and improve the disease-free survival rate of mice. The vaccine could increase the proportion of inflammatory cells and decrease the proportion of anti-inflammatory cells in the blood circulation system of mice. In addition, tumor vaccine could also improve inflammatory infiltration in the tumor microenvironment and reduce the proportion of immunosuppressive cells. The results of IHC showed that tumor vaccine could inhibit angiogenesis and tumor cell proliferation in mouse tumor tissues.Conclusion: In colon cancer associated with Lynch syndrome, tumor vaccine can hinder the growth of tumor cells, and assist immunotherapy whose therapeutic effect on this kind of cancer is thus enhanced.

Defects in perovskite films are one of the main factors that affect the efficiency and stability of halide perovskite solar cells (PSCs). Uncoordinated ions (such as Pb2+, I−) act as trap states, causing the undesirable non-radiative recombination of photogenerated carriers. The formation of Lewis acid–base adducts in perovskite directly involves the crystallization process, which can effectively passivate defects. In this work, 4-(trifluoromethyl)-1H-imidazole (THI) was introduced into the perovskite precursor solution as a passivation agent. THI is a typical amphoteric compound that exhibits a strong Lewis base property due to its lone pair electrons. It coordinates with Lewis acid Pb2+, leading to the reduction in defect density and increase in crystallinity of perovskite films. Finally, the power conversion efficiency (PCE) of PSC increased from 16.49% to 18.97% due to the simultaneous enhancement of open-circuit voltage (VOC), short circuit current density (JSC) and fill factor (FF). After 30 days of storage, the PCE of the 0.16 THI PSC was maintained at 61.9% of its initial value, which was 44.3% for the control device. The working mechanism of THI was investigated. This work provides an attractive alternative method to passivate the defects in perovskite.

Abstract (R)-1-[3-(Trifluoromethyl)phenyl]ethanol ((R)-MTF-PEL) is an important chiral building block for the synthesis of a neuroprotective compound, (R)-3-(1-(3-(trifluoromethyl)phenyl)ethoxy)azetidine-1-carboxamide. In this work, an effective whole-cell-catalyzed biotransformation was developed to produce (R)-MTF-PEL, and its productivity was increased by medium engineering strategy. The recombinant E. coli BL21(DE3)-pET28a(+)-LXCAR-S154Y variant affording carbonyl reductase was adopted for the reduction of 3'-(trifluoromethyl)acetophenone to (R)-MTF-PEL with enantiomeric excess (ee) > 99.9%. The addition of 0.6% Tween-20 (w/v) boosted the bioreduction, because the substrate concentration was increased by 4.0-fold than that in the neat buffer solution. The biocatalytic efficiency was further enhanced by introducing choline chloride: lysine (ChCl:Lys, molar ratio of 1:1) in the reaction medium, because the product yield reached 91.5% under 200 mM substrate concentration in the established Tween-20/ChCl:Lys-containing system, which is the highest ever reported for (R)-MTF-PEL production. The optimal reduction conditions were as follows: 4% (w/v) ChCl:Lys, 12.6 g (DCW)/L recombinant E. coli cells, pH 7.0, 30 ℃ and 200 rpm, reaction for 18 h. The combined strategy of surfactant and NADES has great potential in the biocatalytic process and the synthesis of chiral alcohols.

ABSTRACT Streptococcus suis is an important zoonotic bacterial pathogen posing a threat to the pig industry as well as public health, for which the mechanisms of growth and cell division remain largely unknown. Developing convenient genetic tools that can achieve strictly controlled gene expression is of great value for investigating these fundamental physiological processes of S. suis. In this study, we first identified three strong constitutive promoters, Pg, Pt, and Pe, in S. suis. Promoter Pg was used to drive the expression of repressor genes tetR and lacI, and the operator sequences were added within promoters Pt and Pe. By optimizing the insertion sites of the operator sequence, we successfully constructed an anhydrotetracycline (ATc)-inducible expression system and an isopropyl-β-d-thiogalactopyranoside (IPTG)-inducible expression system in S. suis. We showed that these two systems provided inducer-concentration- and induction-time-dependent expression of the reporter gene. By using these tools, we investigated the subcellular localization of a key cell division protein, FtsZ, which showed that it could be correctly localized to the midcell region. In addition, we constructed a conditional knockout strain for the glmS gene, which is an essential gene, and showed that our ATc-inducible promoter could provide strictly controlled expression of glmS in trans, suggesting that our inducible expression systems can be used for deletion of essential genes in S. suis. Therefore, for the first time we developed two inducible expression systems in S. suis and showed their applications in the study of an important cell division protein and an essential gene. These genetic tools will further facilitate the functional study of other important genes of S. suis. IMPORTANCE Streptococcus suis is an important zoonotic bacterial pathogen. Studying the mechanisms of cell growth and division is important for the identification of novel antimicrobial drug targets. Inducible expression systems can provide strictly controlled expression of the protein of interest and are useful tools to study the functions of physiologically important proteins. However, there is a lack of convenient genetic tools that can achieve inducible protein expression in S. suis. In this study, we developed two (ATc-inducible and IPTG-inducible) inducible expression systems and showed their applications in a subcellular localization study of a cell division protein and the construction of conditional knockout of essential genes in S. suis. These systems will be useful for functional studies of important proteins of S. suis.

The aim of this study was to evaluate the effect of Bacillus cereus (B. cereus) on the seedling growth and accumulation of medicinal ingredients of Glycyrrhiza uralensis Fisch. (G. uralensis) under control and salt stress conditions. Our results revealed the different effects of B. cereus on the seedling growth and accumulation of medicinal ingredients particularly in different conditions based on the transcriptome and polymerase chain reaction (PCR) analysis. Under the control condition, B. cereus significantly increased the expression level of the β-AS, SQS, CHS, LUS, UGAT, CYP72A154, and CYP88D6 genes and liquiritigenin content. Under salt stress, B. cereus significantly increased root length and lateral root number of G. uralensis seedlings, the expression level of HMGR, β-AS, CHS, LUS, UGAT, CYP72A154, CYP88D6, and SE genes, and the contents of glycyrrhizic acid and glycyrrhetinic acid. Notably, the effect of B. cereus on the seedling growth and the medicinal ingredient biosynthesis was different under control and salt stress conditions. Specifically, the effect of B. cereus on the seedling growth under salt stress was greater than that under the control condition. Moreover, B. cereus increased liquiritigenin content under the control condition, which is closely related to flavone and flavonol biosynthesis, while it increased the contents of glycyrrhizic acid and glycyrrhetinic acid under salt stress, which is closely related to phenylpropanoid biosynthesis, and the MVA pathway is also involved. All in all, endophytes B. cereus could be used as a sustainable tool to develop effective bioinoculants to enhance the contents of medicinal ingredients in G. uralensis.

Polybrominated biphenyls (PBBs) can bioaccumulate in nature and are toxic to humans. Long-time exposure to PBBs in pregnant women can lead to the birth of an infant with abnormal conditions. Hence, in this study, we used molecular docking, molecular dynamics, Taguchi experimental design, and fractional factorial experimental design to identify the developmental toxicity characteristics of 10 typical developmental toxic pollutants such as PBBs to which humans are frequently exposed. Furthermore, the correlation and sensitivity analyses of molecular developmental toxicity and structural parameters were performed. The molecular key structural parameters of the pollutants affecting human development were screened. Moreover, the supplementary food factors that could alleviate the developmental toxicity of pollutants were screened to develop supplementary food schemes to prevent or alleviate human developmental toxicity in the special population (e.g., pregnant women, infants) exposed to the pollutants. The results showed that the developmental toxicity was controlled by the main effects of the 10 pollutants. Among the 10 pollutants with developmental toxicity, the most significant pollutant with the main effects was PBB-153 (37.06%). In addition, the correlation and sensitivity analyses of the molecular developmental toxicity of the pollutants and structural parameters showed that the total energy value and infrared C–H vibration frequency of the pollutants were significantly correlated with human developmental toxicity. Accordingly, 15 supplementary food cofactors were selected for the Taguchi experiment design, among which the top seven cofactors were designed by fractional factorial analysis. The most significant cofactor that alleviated the developmental toxicity of PBB-153 exposure was the combination of carotene and docosahexaenoic acid (DHA), with an improvement of 17.28%. The combination of carotene and DHA significantly alleviated the effects of toxicity caused by most of the other pollutants, indicating that the selected supplementary food has certain universality. In this study, we developed a method to identify the characteristics of the developmental toxicity of pollutant exposure and developmental toxicity alleviation. Our study provided theoretical support for the regulation strategy of developmental toxicity caused by pollutants such as PBBs.