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The IR spectra of CH 3 AsH 2 at CAM-B3LYP/cc-PVQZ theoretical level are plotted considering the harmonic and anharmonic vibrational approximations, the peaks of the IR spectrum of CH 3 AsH 2 are significantly red-shifted due to the anharmonic effect. [Display omitted] • The spectroscopic constants of CH 3 AsH 2 and CH 2 AsH 3 are calculated and predicted. • The nuclear quadrupole coupling of CH 3 AsH 2 and CH 2 AsH 3 are studied. • The influences of anharmonic effect on their IR spectra are analyzed. The spectroscopic constants and anharmonic force fields of Methylarsine and its isomer are systematically studied by B3LYP, CAM-B3LYP, M06-2X methods utilizing the cc-PVTZ and cc-PVQZ basis sets. The calculated equilibrium geometries, fundamental frequencies, and nuclear quadrupole coupling constants, et al of CH 3 AsH 2 are supported by experimental or theoretical data. The harmonic frequencies, anharmonic constants, et al of CH 3 AsH 2 are predicted for the first time. The anharmonic force fields and spectroscopic constants of CH 2 AsH 3 are also investigated with the same theoretical level. The IR spectra of CH 3 AsH 2 and CH 2 AsH 3 are predicted theoretically, and the red-shifts are found in their peaks. [ABSTRACT FROM AUTHOR]

Investigation into monosaccharides is critical for studies of oligosaccharides structure and function in biological processes. However, monosaccharides quantification is still challenge due to their isomeric structure and high hydrophilic properties. Besides, it was difficult to obtain isotopic internal standards (IS) of each monosaccharide in complex matrixes. Herein, we developed a novel strategy for the qualification and quantification of monosaccharides in urine using two structure analogs 1-(4-methylphenyl)-3-methyl-5-pyrazolone (MPMP) and1-phenyl-3-methyl-5-pyrazolone (PMP) as non-isotopically paired labeling (NIPL) reagents by liquid chromatograph-tandem mass spectrometry (LC-MS/MS). The derivatized monosaccharides by NIPL method not only had sufficient retention time differences on reversed-phase column, but also exhibited predominant product ion pairs (m/z 189 & m/z 175) in the multiple reaction monitoring (MRM) mode. In this method, PMP labeled standards were adopted as one-to-one internal standards (ISs). 12 urinary monosaccharides were successfully determined and the linear ranges expanded five orders of magnitude with limit of quantification (LOQ) varied from 0.09 ng mL−1 to 0.36 ng mL−1 as well as the accuracy higher than 98.15% and the relative standard derivation (RSD) lower than 7.92%. With assistance of multivariate analysis, the targeted monosaccharide biomarkers were firstly obtained for the diagnosis of bladder cancer. By the inexpensive NIPL reagents—MPMP/PMP, the developed strategy possessed the specific advantages of low cost, simple operation, high sensitivity and high accuracy for the qualification and quantitation of monosaccharides. As expected, this method will provide an alternative application potential for targeted metabolomics analysis. [Display omitted] • A new labeling reagent named MPMP was developed for monosaccharides analysis. • Non-isotopically paired labeling (NIPL) reagents-MPMP/PMP were designed for the screening of monosaccharides. • All of 12 monosaccharides labeled by MPMP and PMP were well separated in 21 min. • PMP-labeled monosaccharides were used as one-to-one ISs for absolute quantification. • Targeted monosaccharides closely related to bladder cancer were successfully obtained in visual way. [ABSTRACT FROM AUTHOR]

The anharmonic constants of MNH 2 (M = Li, Na, K) at B3P86/6-311++G (3df, 2pd) theoretical level. The change of metal atoms has no significant influence on the tagged anharmonic constants of MNH 2. [Display omitted] • The spectroscopic properties of NaNH 2 are studied by DFT and MP2. • The B3P86/6-311++G (3df, 2pd) results well reproduce the experimental values. • The spectroscopic properties of KNH 2 are predicted at B3P86/6-311++G (3df, 2pd). • The effects of metal atoms on some spectroscopic constants of MNH 2 are intuitively analyzed. The spectroscopic properties and anharmonic force fields of NaNH 2 are studied in present work by DFT (B3P86 and B3PW91) and MP2 methods in combination with 6-311++G(2d, 2p) and 6-311++G(3df, 2pd) basis sets. The calculated equilibrium geometry, ground state rotational constants and centrifugal distortion constants of NaNH 2 at B3P86/6-311++G(3df, 2pd) theoretical level agree very well with the corresponding experimental values. Noteworthy, some spectroscopic constants and anharmonic force fields of NaNH 2 , which have not been experimentally measured, are firstly predicted. In addition, the spectroscopic properties of KNH 2 are also predicted at the B3P86/6-311++G(3df, 2pd) level of theory. The influences of metal atoms on the equilibrium geometry, anharmonic constants, rotational constants, centrifugal distortion constants of MNH 2 (M = Li, Na, K) are analyzed intuitively. One can find that the metal atoms affect the rotational constants, part of centrifugal distortion constants (D K , D JK , H K , and H KJ), M-N bond length and some anharmonic constants of MNH 2. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to compare clinical outcomes of three therapeutic strategies in patients with stage IB2/IIA2 cervical cancer. Methods. This is a retrospective cohort study. Patients diagnosed with stage IB2/IIA2 cervical cancer between April 2010 and December 2015 at First Affiliated Hospital of Guangxi Medical University were included and classed into three groups. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcomes included toxicity, hospitalization costs, clinical value, and length of stay. Results. 206 patients were included: 104 used primary surgical treatment (PST), 53 used neoadjuvant chemotherapy followed by radical surgery (NAC + RS), and 49 used concurrent chemoradiotherapy (CCRT). Fewer patients with NAC + RS had deep cervical stromal invasion than primary surgical treatment (PST) (P = 0.024). 70.2% of PST and 77.4% in NAC + RS required postoperative radiotherapy or chemoradiotherapy (P = 0.634). Median follow-up was 57 months and the 3-year OS and PFS in PST, NAC + RS, and CCRT group were 87.5%, 84.9%, 85.7% and 85.6%, 79.2%, 85.7% (P = 0.856 and P = 0.424 , respectively). Three therapeutic strategies were not associated with OS and PFS. Hospitalization costs were significantly higher in NAC + RS compared to PST (P < 0.001) and CCRT (P < 0.001). Length of stay in NAC + RS was longer than PST (P < 0.001) and CCRT group (P = 0.07). Conclusion. The results of this study tend to suggest that the three therapeutic strategies were equivalent treatment options for patients with 2009 FIGO stage IB2/IIA2 cervical cancer. However, prospective larger studies are needed to confirm this. In addition, we did find that concurrent chemoradiotherapy needed shorter treatment time and less cost. [ABSTRACT FROM AUTHOR]

The modeling of blind people's behavior is an important topic in pedestrian evacuation dynamics. In order to study movement characteristics of blind people in evacuation process and the effect of indoor obstacles on the evacuation efficiency of blind people, an extended cellular automata model is proposed to simulate blind people evacuation by considering the influence of obstacles. The control variable method is adopted to study the effect of indoor obstacles on the blind evacuation efficiency rule. The numerical simulation is applied to analyze the evacuation process of blind people under different setting (e.g. the location, size and other factors) of obstacles and different evacuation scenarios. The shunt effect of obstacles is discussed and the layout strategy of obstacles is optimized. The results show that the longitudinal obstacles in front of the exit can effectively play the diversion role of obstacles when the obstacle is at a certain distance from the exit, which will improve the evacuation efficiency of the blind. Furthermore, a horizontal obstacle of appropriate length can constrain the trajectory of the blind people and improve the efficiency of evacuation, but when the horizontal obstacle is too long, it will induce extra jam on both sides of the obstacle and hinder the evacuation of the blind. The finding can provide the theoretical basis for the blind people's organization, management and the optimization of evacuation strategies during an emergency. [ABSTRACT FROM AUTHOR]

• Atomic structures of vanadia oxide clusters supported on anatase TiO 2 (1 0 1) surface are predicted. • The structures of vanadia oxide clusters show a coverage-dependent feature. • VO 3 supported on the anatase TiO 2 (1 0 1) surface possesses particularly high reactivity. • NH 3 can only be dissociated on VO 3 /TiO 2 (1 0 1) surface. The atomic structures of VO x clusters supported on anatase TiO 2 (1 0 1) surface (A(1 0 1)) at different coverages are explored based on an evolutionary method. The structures exhibit clear coverage-dependent feature. Unlike those supported on rutile TiO 2 surface, monomeric vanania clusters supported on anatase surface do not favor aggregation. At low coverage, monomeric clusters (VO 2 or VO 3) are the main products, while at higher coverage (≥0.25 ML) polymeric clusters become more popular. Using the hydrogenation energy and oxygen vacancy formation energy as descriptors, and the dissociation of NH 3 as example, the reactivity of each stable structure is studied. The results show that VO 3 /A(1 0 1) possesses particularly high reactivity, and the supporting of V 2 O 5 and V 3 O 6 clusters can also improve the chemical reactivity of A(1 0 1) surface. The molecular adsorption of NH 3 can be enhanced on all the supported V m O n /A(1 0 1) structures, while its dissociation can only occur on VO 3 /A(1 0 1), which implies that the one-site mechanism of the selective catalytic reduction (SCR) reaction of NO x with ammonia only acts at low coverage of vanadium oxide (<0.25 ML). [ABSTRACT FROM AUTHOR]

• The most stable and energetically metastable structures of V–Ti–O monolayer of various compositions on the rutile TiO 2 (011) substrate are predicted, and phase diagram of the V–Ti–O monolayer structures are obtained according to the calculated formation energies. • The predicted V–Ti–O structures can be considered as V-doped reconstruction of rutile TiO 2 (011) surface. Some new energetically stable reconstructions were predicted, which enrich the reconstruction models of rutile TiO 2 (011) surface. • The electronic structures of all the predicted structures and the oxidation states of V and Ti atoms in them are determined, which is important for understanding the mechanism of V doping to improve the photocatalytic properties of TiO 2. The formation of various structural V–Ti–O intermixed oxide monolayers on the rutile TiO 2 (011) substrates have been observed in experiments. The atomic structures and formation mechanism of them are still unclear. To this end, a global search of V–Ti–O ordered structures on rutile TiO 2 (011) surface is performed based on the evolutionary method. Nine energetically stable or metastable structures of different compositions are predicted, which can be considered as V-doping in different type of 2 × 1 reconstruction of rutile TiO 2 (011) surface. The calculated electronic structures indicate that the V atoms in most structures are not fully oxidized and introduce localized impurity states in the band gap. The oxidation states of the V atoms and surface Ti atoms are determined. The stabilization regions of them are determined based on the calculated surface energies. Our results are instructive for the experimental synthesis of different structural V–Ti–O monolayers, and significant for deep understanding of the photo- or electro-catalytic properties of them. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Corticotropin-releasing factor (CRF) and the three related peptides urocortins 1–3 (UCN1–UCN3) are endocrine hormones that control the stress responses by activating CRF1R and CRF2R, two members of class B G-protein-coupled receptors (GPCRs). Here, we present two cryoelectron microscopy (cryo-EM) structures of UCN1-bound CRF1R and CRF2R with the stimulatory G protein. In both structures, UCN1 adopts a single straight helix with its N terminus dipped into the receptor transmembrane bundle. Although the peptide-binding residues in CRF1R and CRF2R are different from other members of class B GPCRs, the residues involved in receptor activation and G protein coupling are conserved. In addition, both structures reveal bound cholesterol molecules to the receptor transmembrane helices. Our structures define the basis of ligand-binding specificity in the CRF receptor-hormone system, establish a common mechanism of class B GPCR activation and G protein coupling, and provide a paradigm for studying membrane protein-lipid interactions for class B GPCRs. • Two cryo-EM structures of CRF1R and CRF2R bound to UCN1 and Gs heterotrimer • Mechanisms of the N-terminal residues of UCN1 in receptor binding and activation • Comparison with the inactive structure reveals conformational changes upon activation • The important role of cholesterols in GPCR signaling is further established The fully active structures of CRF receptors reveal the basis for peptide-binding specificity, support a universal mechanism of class B GPCR activation, and provide detailed structural information for studying membrane protein-lipid interactions. [ABSTRACT FROM AUTHOR]

Three new copolymer donors based on DCN-alt FTAZ PT-68, PT-810-H, and PT-810-L were synthesized by adjusting the alkyl chains and molecular weight. The copolymers showed deep highest occupied molecular orbital (HOMO) levels of about −5.50 eV due to introducing fluorine atoms and cyano electron-withdrawing groups. Therefore, devices based on the copolymers as donors and ITIC as acceptors had high open-circuit voltages (V OC) exceeding 1.00 V. Due to a dicyanodistyrylbenzene (DCN) unit providing rigid and extended conjugation and reducing the backbone torsion, the blended films had high hole mobility values of about 2.50 × 10−3 cm2 V−1 s−1. Devices with the PT-810: ITIC blended film had the highest power conversion efficiency (PCE) of 7.03%, with an open-circuit voltage of 1.04 V, a short-circuit current density of 12.25 mA/cm2, and a fill factor of 55%. These results provide guidance for the design of high-efficiency photovoltaic materials. Benzotriazole-based medium bandgap copolymer donors were synthesis, which show deep HOMO levels of about −5.50 eV. A PCE of 7.03% was obtain with the device based on PT-810-H: ITIC, with a high open-circuit voltage (V OC) exceed 1.00 V and high hole mobility value about 2.50 × 10−3 cm2 V−1 s−1. Image 1 • The devices have high V oc exceeding 1.00 V. • The effects of the side alkyl chains and molecular weight on the properties of the copolymers are studied. • The deep HOMO levels achieve due to introducing fluorine atoms and cyano electron-withdrawing groups. [ABSTRACT FROM AUTHOR]

Carbon fabric/resin laminated composites (CFRC) are extensively used in aerospace, transportation, and other fields owing to their superiorities of lightweight, high strength, and convenient integral molding. Therefore, strong interlaminar binding and prominent wear resistance are urgent requirements for avoiding premature failure of laminated materials in harsh working environments. To elevate the superficial wear resistance and interlaminar bonding strength of composites simultaneously, the modified composites were obtained by introducing carbon fiber powder (CFP) with different densities on the surface of the composites and between layers. The experimental results indicate that CFP can be evenly distributed in the interlaminar resin enrichment zone of the sample (CFRC‐40) when the deposition density is 40 g/m2. Consequently, CFRC‐40 presents optimal thermal conductivity owing to better heat transfer bridges between layers of the composite established by CFP. At the same time, the mechanical properties such as the tensile, impact, and interlaminar shear strengths of CFRC‐40 are improved by 42.8%, 10.2%, and 8.5%, respectively, compared with the original CFRC, which are attributed to the absorption of crack propagation energy and the inhibition of crack propagation by CFP. Furthermore, the dynamic friction coefficient maintains at a high level after introducing CFP with a density of 40 g/m2, while the wear rate significantly decreases by 61.2% from 12.99 × 10−14 m3(N m)−1 to 5.04 × 10−14 m3(N m)−1. This study proposes an innovative strategy to improve the interlaminar bonding of carbon fabric/resin laminated composite, which is conducive to obtaining composite with excellent mechanical and tribological properties. Highlights: A facile and effectual method was adopted to introduce carbon fiber powder (CFP) into the interlamination and surface of the composites simultaneously.The mechanical properties and abrasive resistance of the composites were obviously strengthened by regulating the content and distribution of CFP.CFP at a certain scale, could not only hinder the propagation of cracks but also alleviate the surface wear and extend the service life of composites. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are involved in the occurrence and development of human cancers including lung adenocarcinoma (LUAD). SLC2A1-AS1 is a novel lncRNA that has been reported to be exceptionally expressed in several cancer types. However, the expression and role of SLC2A1-AS1 in cancer remains largely unclear. In this study, it was revealed that lncRNA SLC2A1-AS1 was notably over-expressed in LUAD and was closely correlated with patients' overall survival (OS). Knockdown of SLC2A1-AS1 could significantly restrain cell proliferation of LUAD in vitro, while over-expression of SLC2A1-AS1 had the accelerative effect. SLC2A1-AS1 enriched in the cytoplasm of LUAD cells could directly bind to miR-508-5p and negatively regulate its level. The inhibitory effect of miR-508-5p on LUAD cell proliferation was in part abrogated by SLC2A1-AS1 manipulation. Moreover, the transcription factor activating enhancer binding protein 2 α (TFAP2A) was highly expressed in LUAD and predicted worse patients' OS. TFAP2A could directly bind to the promoter region of SLC2A1-AS1 encoding gene and positively regulate the transcription of SLC2A1-AS1 in LUAD cells. Furthermore, TFAP2A-induced SLC2A1-AS1 promoted cell proliferation of lung squamous cell carcinoma (LUSC) and pancreatic adenocarcinoma (PAAD). Collectively, these findings suggest that TFAP2A-mediated lncRNA SLC2A1-AS1 works as an oncogene to drive cancer cell proliferation. [ABSTRACT FROM AUTHOR]

Selenium (Se) might be protective against oxidative stress at nutritional levels, but elevated Se concentrations in the diet has been revealed as the main culprit for the extinction of natural fish populations in Se-contaminated lakes. Though Se predominate as waterborne selenite (IV) and selenate (VI) in the water, the differences in bioaccumulation, effects (e.g., oxidative stress, antioxidants etc.) and molecular mechanisms between Se(IV) and Se(VI) have been relatively understudied in wild fish. In this study, the P. parva were exposed to waterborne Se (10, 200 and 1000 μg/L of Se(IV) or Se(VI)) and sampled at 4, 14 and 28 days. Bioaccumulation, tissue distributions of Se and following effects in different tissues were evaluated. The results showed that the levels of Se in the gills and intestine were significantly elevated with a seemingly concentration-dependent pattern in the Se(IV) treatment, with respectively 173.3% and 57.2% increase after 28 days of exposure, relative to that of Se(VI) treatment. Additionally, significant accumulation of Se was also observed in the muscle of Se(IV) treated fish. Se exposure increased the MDA levels in the brain and gills in the Se(IV) treatment, but less apparent in the Se(VI) treatment. Meanwhile, Se exposure lowered (at least 56%) the activity of GST in the gills, but increased the activity of AChE in the muscle (~69%) and brain (~50%) after 28 d. Most importantly, after 28 d of exposure, Se exposure caused significant decrease in GSH levels in the gills (at least 35%) and in all tissues examined at the highest test concentration. In general, the results showed that Se(IV) led to faster accumulation of Se than Se(VI) in P. parva, and the resulted lipid peroxidation was closely related to the levels of antioxidants, especially GSH. Our results suggest that the ecotoxicological effects of waterborne selenite and selenate differ in this freshwater species in the field. [ABSTRACT FROM AUTHOR]

Aberrant microglial activation is a prominent feature of neuroinflammation, which is implicated in the pathogenesis of neurological disorders. Fc receptor common γ-chain (FcRγ), one of the two immunoreceptor tyrosine-based activation motif-bearing adaptor proteins, is abundantly expressed in microglia. It couples with different receptors, such as receptors for the Fc portion of IgG. In this study, we observed increased FcRγ expression along with increased IgG-binding during acute neuroinflammation triggered by MPTP intoxication, where adaptive immune responses should not be involved. Notably, FcRγ was expressed not only in the cell membrane but also in the cytoplasm in the activated microglia. FcRγ deficiency exacerbated microglial activation, pro-inflammatory factor upregulation, nigral dopaminergic neuronal loss and motor deficits, implicating a beneficial role of FcRγ in this model. Blockade of Fcγ receptor ligation by IgG in mice by Endoglycosidase S treatment, a bacterial endo-β-N-acetylglucosaminidase cleaving specifically the Asn297-linked glycan of IgG, or by using the mice deficient in mature B cells (muMT) with IgG production defects, did not show similar phenotypes to those observed in FcRγ-deficient mice, indicating that the beneficial effect mediated by FcRγ did not depend on FcγR ligation by IgG. Further, FcRγ knockout aggravated the expression and activation of STAT1 in microglia, suggesting FcRγ modulated neuroinflammation by dampening STAT1 signaling. Collectively, these results revealed that FcRγ-associated receptors could function as negative regulators of neuroinflammation and dopaminergic neurodegeneration. • FcRγ is expressed predominantly in microglia and upregulated after MPTP treatment. • FcRγ KO exacerbates subacute MPTP treatment-induced neuroinflammation. • FcRγ KO exacerbates subacute MPTP treatment-induced dopaminergic neurodegeneration. • FcRγ KO aggravates MPTP-induced microglial STAT1 activation. • FcRγ-mediated modulation of neuroinflammation is independent of FcγR ligation by IgG. [ABSTRACT FROM AUTHOR]

Previous studies have shown that cancer susceptibility candidate 5 (CASC5) plays important roles in several types of cancer. But its expression and clinical significance in human pan‐cancer remain largely unclear. In the present study, we comprehensively analysed the expression profile and prognostic values of CASC5 in pan‐cancer across 33 cancer types based on the online TCGA analysis databases. CASC5 was found to be abnormally expressed in 16 types of cancer. In addition, dysregulated expression of CASC5 was closely associated with patient overall survival (OS) in kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD) and thymoma (THYM). By comparative analysis, we found that CASC5 was significantly up‐regulated in LUAD and predicted poor patient OS. High CASC5 expression was closely correlated with tumour advanced stages of patients with LUAD. Through GSEA based on the KEGG database, CASC5 was found to be closely related to DNA replication and microRNA regulation in LUAD. Functionally, knockdown of CASC5 could inhibit cell proliferation of LUAD cells in vitro, rather than affecting cell migration and invasion. Mechanistically, CASC5 promoted proliferation of LUAD cells by targeting miR‐139‐5p. Collectively, our findings reveal that CASC5 is a novel oncogenic gene in LUAD and may be a potential clinical target and (or) biomarker for this human malignancy. Significance of the study: In this study, we for the first time comprehensively analysed the transcriptional level and prognostic significance of CASC5 in human pan‐cancer across 33 cancer types using online TCGA databases. Our study indicates that CASC5 is aberrantly expressed in many tumours and is closely related to the patient overall survival of several tumour types. Our findings reveal that CASC5 is a novel oncogene in LUAD based on bioinformatic analysis and functional experiments. Mechanistically, CASC5 promoted LUAD proliferation by targeting miR‐139‐5p. Results of this study suggest that CASC5 is a potential clinical target and (or) biomarker for LUAD. [ABSTRACT FROM AUTHOR]

This paper addresses the pricing and coordination strategy in a green supply chain in which a manufacturer produces a green product and sells it to a risk-averse retailer. The product's demand is a random variable influenced by the green level and the retail price. The problem is modeled in three different structures, a centralized and two decentralized models, in which the upstream manufacturer and the downstream retailer act as the channel leader, respectively. This paper presents the optimal decisions for all supply chain members, analyzes the effects of green degree and risk-averse coefficient on the supply chain members' decision-making and their profits, and performs the numerical analysis. The results show that the green degree and the whole supply chain's expected profits are highest in the centralized scenario, followed by the retailer-led scenario, and lowest under the manufacturer-led scenario; the green degree and the manufacturer's expected profit increase with the risk-averse coefficient, no matter who dominates the channel; however, the risk-averse coefficient's effects on the retailer's expected utility and the retail price depends on who dominates the channel and on the greening investment parameter. [ABSTRACT FROM AUTHOR]

Background: Adult secondary hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome characterized by excessive activation of mononuclear-phagocytic system resulting in hyperinflammatory response. To date, the factors influencing early death of HLH are still not fully elucidated. Patients and Methods: We did a retrospective study of 171 adult patients with newly diagnosed HLH at our institution from January 2012 to April 2018. All patients' clinical features, laboratory findings, treatments and prognosis were reviewed. Results: The median age was 49 years (range, 18–88 years), and 110 (64.3%) were male. The major underlying trigger of HLH was malignancy (88/171, 51.5%), especially non-Hodgkin lymphoma. In a multivariate analysis, age ≥54 years (P = 0.002), platelet ≤39.5 × 109/L (P = 0.028), activated partial thromboplastin time (APTT) ≥54 sec (P = 0.048), triglyceride ≥3.23 mmol/L (P < 0.001), lactate dehydrogenase (LDH) ≥1300 U/L (P = 0.012) and malignancy (P = 0.001) were significantly associated with early death in HLH. Then, patients were classified into four groups according to the number of risk factors at the time of diagnosis: low risk (zero, one or two risk factors), low intermediate risk (three risk factors), high intermediate risk (four risk factors) and high risk (at least five risk factors), with the 30-day overall survival (OS) of 92.4%, 58.8%, 30.0% and 4.8%, respectively (P < 0.001). Conclusions: Patients with old age, thrombocytopenia, prolonged APTT, hypertriglyceridemia, elevated LDH and malignancy had inferior survival. It is important to identify those patients at risk of early death, which may guide treatment and reduce mortality. [ABSTRACT FROM AUTHOR]

In this paper we investigate viscosity solutions of non-divergence elliptic equations in cones and obtain asymptotic behaviors at vertexes of cones and at infinity of solutions. [ABSTRACT FROM AUTHOR]

Purpose: The prognostic factors for diffuse large B‐cell lymphoma (DLBCL) have been fully explored, but prognostic information for bulky mass DLBCL patients is limited. This study aimed to analyze the prognostic value of MYC protein expression and other biological parameters in bulky mass DLBCL patients. Methods: We defined a bulky mass as a maximum tumor diameter ≥7.5 cm and studied 227 patients with de novo bulky mass DLBCL. Results: In all patients with bulky mass DLBCL, the 1‐year and 3‐year OS rates were 72.7% and 57.1%, respectively, and the 1‐year and 3‐year PFS rates were 52.0% and 42.5%, respectively. The MYC overexpression group (n = 140) showed significantly worse overall survival (OS; p = 0.019) and progression‐free survival (PFS; p = 0.001) than the non‐MYC overexpression group (n = 87). Subgroup analyses demonstrated that the MYC overexpression group was associated with inferior OS and PFS in the subgroups with the International Prognostic Index score of 3–5 (OS: p = 0.011; PFS: p < 0.001), Ann Arbor stage 3–4 (OS: p = 0.014; PFS: p < 0.001) and GCB subtype (OS: p = 0.014; PFS: p = 0.010). Consolidation radiotherapy improved OS and PFS in patients with bulky mass DLBCL (OS: p = 0.008; PFS: p = 0.004) as well as in those with MYC overexpression (OS: p = 0.001; PFS: p = 0.001). The prognostic value of MYC overexpression was maintained in a multivariate model adjusted for the International Prognostic Index. Conclusion: MYC overexpression is a poor predictor for bulky mass DLBCL patients. Consolidation radiotherapy for residual disease after induction therapy may improve outcomes for patients with bulky mass DLBCL. [ABSTRACT FROM AUTHOR]

Purpose: To report a rare type of Pallister-Killian syndrome (PKS) diagnosed prenatally by the utility of non-invasive prenatal testing (NIPT). Methods: NIPT was performed in the first trimester. Conventional karyotyping and chromosomal microarray analysis (CMA) were performed on the amniotic samples in the second trimester. Copy number variation sequencing (CNV-seq) was used for the validation of fetal skin and the placental tissue after pregnancy termination. Results: NIPT results showed increased signal from chromosome 12p. Subsequent prenatal diagnostic testing by karyotype revealed 47, XY, +i (12p), and CMA displayed four copies of 12p: 12p13.33-12p11.1(173786_34835641) × 4. The CNV-seq results of the fetal skin and the fetal side of placenta showed four copies of 12p13.33-p11 and an estimated chimeric duplication of 34.08 Mb (chimerism ratio: 10%) in 12 p13.33-p11, respectively. However, no abnormality was detected by CNV-seq at the maternal side of placenta. Conclusions: Our findings suggest that a positive signal from chromosome 12p on NIPT should raise suspicion for PKS. With the wide application of NIPT, the true positive of incidental finding is expected to increase. [ABSTRACT FROM AUTHOR]

Keratinocytes are the predominant cell type in the skin epidermis, and they not only protect the skin from the influence of external physical factors but also function as an immune barrier against microbial invasion. However, little is known regarding the immune defence mechanisms of keratinocytes against mycobacteria. Here, we performed single‐cell RNA sequencing (scRNA‐seq) on skin biopsy samples from patients with Mycobacterium marinum infection and bulk RNA sequencing (bRNA‐seq) on M. marinum‐infected keratinocytes in vitro. The combined analysis of scRNA‐seq and bRNA‐seq data revealed that several genes were upregulated in M. marinum‐infected keratinocytes. Further in vitro validation of these genes by quantitative polymerase chain reaction and western blotting assay confirmed the induction of IL‐32 in the immune response of keratinocytes to M. marinum infection. Immunohistochemistry also showed the high expression of IL‐32 in patients' lesions. These findings suggest that IL‐32 induction is a possible mechanism through which keratinocytes defend against M. marinum infection; this could provide new targets for the immunotherapy of chronic cutaneous mycobacterial infections. [ABSTRACT FROM AUTHOR]

Phenylketonuria (PKU) is the most common inherited metabolic disease, an autosomal recessive disorder affecting >10,000 newborns each year globally. It can be caused by over 1000 different naturally occurring mutations in the phenylalanine hydroxylase ( PAH ) gene. We analyzed three novel naturally occurring PAH gene variants: p.Glu178Lys (c.532G>A), p.Val245Met (c.733G>A) and p.Ser250Phe (c.749C>T). The mutant effect on the PAH enzyme structure and function was predicted by bioinformatics software. Vectors expressing the corresponding PAH variants were generated for expression in E. coli and in HEK293T cells. The RNA expression of the three PAH variants was measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The mutant PAH protein levels were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), western blot and enzyme-linked immunosorbent assay (ELISA). All three variants were predicted to be pathogenic by bioinformatics analysis. The transcription of the three PAH variants was similar to the wild type PAH gene in HEK293T cells. In contrast, the levels of mutant PAH proteins decreased significantly compared to the wild type control, in both E. coli and HEK293T cells. Our results indicate that the three novel PAH gene variants (p.Glu178Lys, p.Val245Met, p.Ser250Phe) impair PAH protein expression and function in prokaryotic and eukaryotic cells. [ABSTRACT FROM AUTHOR]

Based on the first principles calculations, we have studied the electronic and optical properties of 3 d transition metal atoms (TM = Sc, Ni, Cu, Zn) adsorbed on the surface of monolayer SnSe 2. The results show that SnSe 2 adsorbed with Ni and Cu are direct band gap semiconductors with band gaps of 0.324 eV and 0.501 eV, respectively, while SnSe 2 adsorbed with Sc and Zn are indirect band gap semiconductors with band gaps of 0.728, 0.531 eV. The band gaps of all adsorbed structures are reduced to different degrees compared to the pristine SnSe 2. After the adsorption of transition metal atoms by SnSe 2 , the imaginary part of the dielectric function shifts to the lower energy region and the peak decreases compared to the pristine SnSe 2. The absorption coefficients of TM/SnSe 2 are significantly higher in the visible (1.64 eV–3.19 eV) and infrared ranges, with Ni/SnSe 2 having a larger absorption coefficient near 1.64 eV than the other TM atoms. In the z-direction, Sc/SnSe 2 has a peak at 2.51 eV with an absorption coefficient of 7.83 × 104/cm. The results show that the optical properties of SnSe 2 can be adjusted by adsorption of transition metal atoms to improve absorption in the long-wave light range, which has potential applications in the field of photoelectric devices. • The adsorbed band gaps are reduced to different degrees compared to the pristine SnSe 2. • After the adsorption of transition metal atoms, the imaginary part of the dielectric function shifts to the lower energy region and the peak decreases. • The absorption coefficients of TM/SnSe 2 are significantly higher in the visible light and infrared light ranges. • The absorption coefficients of Ni/SnSe2 have the largest absorption coefficient in the infrared light range. • The optical properties of SnSe 2 can be adjusted by adsorption of transition metal atoms. [ABSTRACT FROM AUTHOR]

[Display omitted] • ZIS/CFO flower-like composites were prepared by a method involving ultrasonic and calcination. • Charge carriers were separated due to the formed p-n heterojunction and internal electric field. • Magnetic ZIS/CFO can be recovered under the external magnetic field. The construction of a p-n heterojunction structure is considered to be an effective method to improve the separation of electron-hole pairs in photocatalysts. A series of ZnIn 2 S 4 /CoFe 2 O 4 (ZIS/CFO) photocatalysts with p-n heterojunctions were prepared via a method involving ultrasonication and calcination. The synthesized photocatalysts were tested and analyzed via various testing techniques, and their hydrogen evolution rates were evaluated. Compared with pure ZIS, ZIS/CFO with different mass ratios of CFO to ZIS showed improved photocatalytic hydrogen production performance, and the optimal photoactivity showed a nearly 12-fold increase, which can be attributed to the formation of p-n junctions and the formed internal electric field, accelerating the separation of electron-hole pairs and effectively improving the photocatalytic hydrogen evolution rate. The excellent stability of the ZIS/CFO composite was proven by three cycle experiments. In addition, the ZIS/CFO composite also possessed excellent magnetic properties to realize facial magnetic recoverability. This work paves the way for the design and preparation of magnetically recoverable p-n heterojunction photocatalysts. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are common, incurable neurological disorders with high prevalence, and lead to memory, movement, language, and intelligence impairments, threatening the lives and health of patients worldwide. The blood–brain barrier (BBB), a physiological barrier between the central nervous system and peripheral blood circulation, plays an important role in maintaining the homeostasis of the intracerebral environment by strictly regulating the transport of substances between the blood and brain. Therefore, it is difficult for therapeutic drugs to penetrate the BBB and reach the brain, and this affects their efficacy. Nanoparticles (NPs) can be used as drug transport carriers and are also known as nanoparticle-based drug delivery systems (NDDSs). These systems not only increase the stability of drugs but also facilitate the crossing of drugs through the BBB and improve their efficacy. In this article, we provided an overview of the types and administration routes of NPs, highlighted the preclinical and clinical studies of NDDSs in neurodegenerative diseases, and summarized the combined therapeutic strategies in the management of neurodegenerative diseases. Finally, the prospects and challenges of NDDSs in recent basic and clinical research were also discussed. Above all, NDDSs provide an inspiring therapeutic strategy for the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Long non‑coding RNAs (lncRNAs) are defined as non‑coding transcripts (>200 nucleotides) that serve important roles in the proliferation and differentiation of stem cells. Hair follicle stem cells (HFTs) have multidirectional differentiation potential and are able to differentiate into skin, hair follicles and sebaceous glands, serving a role in skin wound healing. The aim of the present study was to analyze the regulatory role of lncRNA AK015322 (IncRNA5322) in HFTs and the potential mechanism of IncRNA5322‑mediated differentiation of HFTs. The results demonstrated that lncRNA5322 transfection promoted proliferation and differentiation in HFTs. It was identified that lncRNA5322 transfection upregulated the expression and phosphorylation of phosphoinositide 3‑kinase (PI3K) and protein kinase B (AKT) in HFTs. It was also observed that lncRNA5322 transfection upregulated microRNA (miR)‑21 and miR‑21 agonist (agomir‑21) eliminated lncRNA5322‑induced expression and phosphorylation of PI3K and AKT. The present study also demonstrated that agomir‑21 blocked IncRNA5322‑induced expression and phosphorylation of PI3K and AKT in HFTs. The results indicated that agomir‑21 transfection also suppressed the IncRNA5322‑induced proliferation and differentiation of HFTs. In conclusion, the results of the present study suggest that lncRNA5322 is able to promote the proliferation and differentiation of HFTs by targeting the miR‑21‑mediated PI3K‑AKT signaling pathway in HFTs. [ABSTRACT FROM AUTHOR]

Using microalgae to treat wastewater has received growing attention in the world because it is regarded as a novel means for wastewater treatment. It is commonly recognized that large-scale cultivation and commercial application of microalgae are limited by the development of photobioreactor (PBR). Although there are a lot of PBRs for microalgae pure cultivation which used culture medium, specialized PBRs designed for wastewater treatment are rare. The composition of wastewater is quite complicated; this might cause a very different photosynthetic effect of microalgae compared to those grown in a pure cultivation medium. Therefore, PBRs for wastewater treatment need to be redesigned and improved based on the existing PBRs that are used for microalgae pure cultivation. In this review, different PBRs for microalgae cultivation and wastewater treatment are summarized. PBR configurations, PBR design parameters and types of wastewater are presented. In addition, the wastewater treatment efficiency and biomass productivity were also compared among each type of PBRs. Moreover, some other promising PBRs are introduced in this review, and a two-stage cultivation mode which combines both closed and open system is discussed as well. Ultimately, this article focuses on current problems and gives an outlook for this field, aiming at providing a primary reference for microalgae cultivation by using wastewater. [ABSTRACT FROM AUTHOR]

The incidence of cognitive impairment is rising globally, but there is no effective therapy. Recent studies showed that fucoidan (Fuc), a sulfated polysaccharide enriched in brown algae, is widely used due to its anti-inflammatory, antioxidant, and prebiotic effects. However, the effects and mechanisms of Fuc on lipopolysaccharide (LPS)-induced neuronal cell damage and cognitive impairment in mice need to be explored further. In the present study, we found that Fuc treatment protected HT22 cells from LPS-induced damage by inhibiting the activation of NLRP3 inflammasomes. Fuc exerted neuroprotective effects in mice with LPS-induced cognitive impairment by ameliorating neuroinflammation, promoting neurogenesis, and reducing blood-brain barrier and intestinal barrier permeability. Mechanistically, Fuc supplement significantly restructured the gut microbiota composition, which may be related to glucose and fructose metabolism. In conclusion, Fuc ameliorated LPS-induced neuronal cell damage and cognitive impairment in mice, suggesting that Fuc may be a medicinal and food homologous functional agent to improve cognitive function. The possible mechanism by which Fucoidan ameliorates LPS-induced cognitive impairment in mice, especially by remodeling gut microbiota. [Display omitted] • Fuc protected HT22 cells from LPS-induced damage via the inhibition of NLRP3 inflammasome. • Fuc exerted neuroprotective effects on LPS-induced cognitive impairment by reducing BBB and gut permeability. • Fuc remodeled the gut microbiota, which may be related to glucose and fructose metabolism. [ABSTRACT FROM AUTHOR]

The successful demonstration of monolayer films as promising thermoelectric materials highlights alternative strategies to nanostructuring for achieving high thermoelectric efficiency. Due to this reason, the electronic structure and thermoelectric properties of the monolayer Sb2Te3 are studied by using the density functional theory and the semiclassical Boltzmann transport equation. The dynamical stability of the monolayer Sb2Te3 can be guaranteed by the absence of imaginary frequencies in the phonon band structure. The monolayer Sb2Te3 can reduce the lattice thermal conductivity. The Seebeck coefficient S of the p-type monolayer Sb2Te3 is almost three times as high as those of the n-type monolayer Sb2Te3. The power factor for p-type doping is significantly larger than that for the n-type doping. Our calculated ZT values for the monolayer Sb2Te3 are far higher than those of nanomaterials Sb2Te3, bulk Sb2Te3, and the eutectic PbTe-Sb2Te3 composites, indicating that the thermoelectric performance of low-dimensional structure is indeed superior. [ABSTRACT FROM AUTHOR]

The combination of monolayer transition metal dichalcogenides (TMDCs) and the periodic nanostructures allows the great chance to bring great breakthroughs in their optical properties, such as, exciton-polaritons and photoluminescence. Here we show the improved light-matter interaction, as manifested in enhanced Goos-Hänchen (GH) shift, in monolayer MoS 2 based symmetric and asymmetric dielectric grating structures. It is found that the GH shifts can be drastically enhanced when monolayer MoS 2 is bridged onto the symmetric and asymmetric dielectric grating layer, whose enhancement can be attributed to the excitation of the guided mode resonance in the dielectric grating layer. In particular, in comparison with the case of the symmetric dielectric grating with monolayer MoS 2 , the asymmetric grating with monolayer MoS 2 has achieved the GH shift as high as 9490 λ , which is about three times larger than that in the former structure. In addition, the magnitude and the sign of the GH shift can be controlled by the asymmetric factor and other geometrical parameters in the dielectric grating layer. Our work uncovers an alternative approach to improve and engineer the GH shift of layered TMDC semiconductors via the help of the dielectric grating structures, which might greatly facilitate their utilizations in optoelectric and photonic fields. [ABSTRACT FROM AUTHOR]

Peripheral blood stem cell (PBSC) collection has been increasingly more popular than bone marrow donation, but little side effects induced by hemogram variation of donors for PBSC collection were reported. The peripheral blood cells were counted pre- and post-collection of PBSC from 166 allogeneic-related donors. Donors' hemoglobin concentration decreased from 144.95 (±16.175) g/L to 139.12 (±13.684) g/L ( P < 0.05) and platelet counts decreased from 234.51 (±60.925) × 109/L to 93.00 (±28.439) × 109/L ( P < 0.001) after sequential PBSC collections. The anemia condition was weakly correlated ( r = 0.297, P < 0.02) and the decrease of platelet counts was strongly correlated ( r = 0.719, P < 0.001) to the blood cells in the collection products. The hemoglobin concentration decrease had no significant difference in all four age groups between pre- and post-collection ( P ≥ 0.05), but was significantly decreased between pre-collection and post-first collection, post-second collection ( P < 0.05 and P < 0.001) in all the body mass index (BMI) groups, among which the underweight group was highly decreased. Neither of the BMI groups nor age groups indicated any statistical difference on platelet counts ( P > 0.05). A slight decrease of hemoglobin and a significant decrease of platelet counts occurred after sequential PBSC collection, which was tolerable for donors younger than 60 years old. The collection characteristic of underweight persons should be fine-tuned to ensure their safety. The platelet decrease was independent of ages or BMI values. [ABSTRACT FROM AUTHOR]

[Display omitted] • Biomimetic fabrication bioprinting strategies based on decellularized extracellular matrix are reviewed. • Fabrication of decellularized extracellular matrix and common 3D Bioprinting Techniques are summarized. • Decellularized extracellular matrix-based bioprinting for musculoskeletal tissue regeneration is overviewed. • The challenge and future perspectives of bioprinting strategies based on decellularized extracellular matrix are prospected. Musculoskeletal disorders, as one of the prevalent categories of ailments, exert significant impacts on individuals' lives, occupations, and physical activities. Degenerative changes, injuries, infections, and tumor resections causing defects in musculoskeletal tissues such as cartilage, bones, skeletal muscles, menisci, ligaments, and rotator cuffs can detrimentally affect patients' quality of life and mental well-being. Traditional autologous and allogeneic transplantations have been clinically employed. However, autologous transplantation suffers from the limitation of a finite number of transplantable tissues, while allogeneic transplantation faces challenges such as immune rejection. The extracellular matrix (ECM) serves as a natural scaffold for cells to fulfill physiological functions such as adhesion, proliferation, and differentiation. Decellularized extracellular matrix (dECM) emerges as a promising biomaterial generated through specific tissue or organ decellularization. Leveraging 3D bioprinting technology, dECM-based biomaterials enable customized printing and construction. This study reviews various decellularization techniques, post-decellularization strategies, and commonly used 3D bioprinting technologies. It summarizes the integration of dECM-based biomaterials with 3D bioprinting technology applied in musculoskeletal system research. These investigations showcase the exciting potential of dECM-based biomaterials in the musculoskeletal system, offering prospects for clinical translation in orthopedics. [ABSTRACT FROM AUTHOR]

• The energy bands of Fe and Mn co-adsorbed monolayers of SnSe 2 exhibit semi-metallicity. • As tensile strain increases, the adsorption system transitions from semi-metallic to metallic, accompanied. • The co-adsorption system's curie temperature is calculated to be 205.2 K. • The application of Fe and Mn double transition metal atoms to monolayer SnSe 2 may have potential. Pure 2D SnSe 2 is not magnetic, which limits its application in spintronics. However, magnetic properties can be induced in pure 2D SnSe 2 by introducing transition metal elements. In this study, we used first-principles calculations based on density-functional theory to predict the electronic structure and magnetic properties of monolayer SnSe 2 under adsorption of Fe and Mn double transition metal atoms. Our findings show that the energy bands of Fe and Mn co-adsorbed monolayers of SnSe 2 exhibit semi-metallicity. As tensile strain increases, the adsorption system transitions from semi-metallic to metallic, accompanied by an increase in total magnetic moment. Based on the Heisenberg model, the co-adsorption system's Curie temperature is calculated to be 205.2 K. Our studies suggest that the application of Fe and Mn double transition metal atoms to monolayer SnSe 2 may have potential in spintronics. [ABSTRACT FROM AUTHOR]

Accurate determination of the electrostatic force exerted on multipole moments is essential in comprehending the interaction between charged bodies and dielectric layers. A comprehensive solution is presented in this study for the calculation of the electric potential, field, and force generated by n th-order electric multipole above a semi-infinite dielectric body covered by a dielectric layer using the image multipole method. The present study investigates the impact of dielectric thickness, permittivity, and separation distance on the electrostatic interaction between an electric multipole moment and a semi-infinite dielectric body. The calculation results indicate that as the thickness of the dielectric layer increases and the dielectric constant of the surrounding medium surpasses that of the dielectric layer, the electrostatic attractive force undergoes a transition to a repulsive force. The magnitude of the electrostatic force acting on a n th-order electric multipole moment is directly proportional to the square of the value of the electric multipole moment and inversely proportional to the 2 (n +1) power of the distance. [ABSTRACT FROM AUTHOR]

Nowadays, two-dimensional materials are ideal for fabricating optoelectronic and spintronic devices. We have investigated the optical and magnetic properties of −6 % to 6 % strain on Mn-adsorbed monolayer SnSe 2 films using a first-principles approach. The Mn-adsorbed monolayer SnSe 2 is a magnetic semiconductor in the absence of strain effects. As the tensile strain increases, the band gap of the Mn-adsorbed monolayer SnSe 2 decreases and the structure becomes unstable, and Mn adsorption changes to exothermic adsorption at −6 % strain. The magnetic moment of the system increases slightly with increasing tensile strain and decreases rapidly when the strain reaches 4%. As the compressive strain increases, the magnetic moment first decreases slightly and then decreases rapidly when the strain reaches −4 %. Calculations of the optical properties show that the static dielectric constants at −6 %, −4 %, −2 %, 0 %, 2 %, 4 % and 6 % strains are 15.23, 10.19, 8.67, 7.78, 6.38, 5.99 and 5.92, respectively, which increase with increasing compressive strain. It decreases with increase in tensile strain. The static dielectric function increases as the compressive strain increases and decreases as the tensile strain increases. In the visible light region, the reflectivity, refractive index, extinction coefficient and photoconductivity in the XX and ZZ directions increase with increasing tensile strain. Our study shows that the optoelectronic and magnetic properties of the SnSe 2 adsorbed Mn system can be improved to some extent by applying strain, and this study is expected to provide theoretical guidance for the fabrication of SnSe 2 -based magnetic optoelectronic devices. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a chronic neurodegenerative disease with high prevalence, long duration and poor prognosis. The blood-brain barrier (BBB) is a physiologic barrier in the central nervous system, which hinders the entry of most drugs into the brain from the blood, thus affecting the efficacy of drugs for AD. Natural products are recognized as one of the promising and unique therapeutic approaches to treat AD. To improve the efficiency and therapeutic effect of the drug across the BBB, a natural polyphenolic compound, procyanidin C-1 (C1) was encapsulated in glucose-functionalized bovine serum albumin (BSA) nanoparticles to construct Glu-BSA/C1 NPs in our study. Glu-BSA/C1 NPs exhibited good stability, slow release, biocompatibility and antioxidant properties. In addition, Glu-BSA/C1 NPs penetrated the BBB, accumulated in the brain by targeting Glut1, and maintained the BBB integrity both in vitro and in vivo. Moreover, Glu-BSA/C1 NPs alleviated memory impairment of 5 × FAD mice by reducing Aβ deposition and Tau phosphorylation and promoting neurogenesis. Mechanistically, Glu-BSA/C1 NPs significantly activated the PI3K/AKT pathway and inhibited the NLRP3/Caspase-1/IL-1β pathway thereby suppressing neuroinflammation. Taken together, Glu-BSA/C1 NPs could penetrate the BBB and mitigate neuroinflammation in AD, which provides a new therapeutic approach targeting AD. Schematic illustration of the synthesis and application of Glu-BSA/C1 NPs in a mouse model of Alzheimer's disease. [Display omitted] [ABSTRACT FROM AUTHOR]

The adverse microenvironment, including neuroinflammation, hinders the recovery of spinal cord injury (SCI). Regulating microglial polarization to alleviate neuroinflammation at the injury site is an effective strategy for SCI recovery. MG53 protein exerts obvious repair ability on multiple tissues damage, but with short half-life. In this study, we composited an innovative MG53/GMs/HA-Dex neural scaffold using gelatin microspheres (GMs), hyaluronic acid (HA), and dextran (Dex) loaded with MG53 protein. This novel neural scaffold could respond to MMP-2/9 protein and stably release MG53 protein with good physicochemical properties and biocompatibility. In addition, it significantly improved the motor function of SCI mice, suppressed M1 polarization of microglia and neuroinflammation, and promoted neurogenesis and axon regeneration. Further mechanistic experiments demonstrated that MG53/GMs/HA-Dex hydrogel inhibited the JAK2/STAT3 signaling pathway. Thus, this MG53/GMs/HA-Dex neural scaffold promotes the functional recovery of SCI mice by alleviating neuroinflammation, which provides a new intervention strategy for the neural regeneration and functional repair of SCI. Schematic illustration of the preparation and application of MG53/GMs/HA-Dex neural scaffolds in a mouse model of spinal cord injury. [Display omitted] • MGHD responded to MMP-2/9 and stably released MG53 protein with good physicochemical properties and biocompatibility. • MGHD improved the motor function of SCI mice, suppressed neuroinflammation, and promoted neurogenesis and axon regeneration. • MGHD inhibited the JAK2/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Joule heating caused by electric currents is a major problem in scale-up electrochromatography. Here, to predict the temperature effects of lateral electric field electrochromatography and the process conditions required, a mathematical heat transfer model was established, which took into account the physical characteristics, including the electrical conductivity, of the porous medium and the ceramic plate in the gel chamber. The temperatures calculated using this model were within 4 °C of the experimentally measured results. For the lateral enlargement simulation of short columns (4 cm), it was found that when the width was enlarged to > 3 cm, the outlet temperature on the center line did not increase with increasing width. The electric field strength of 1700 V/m was maintained by increasing current strength according to the column size; further, when the gel chamber was enlarged to 0.075 × 0.075 × 0.1 m3, its internal temperature can be controlled within 16 °C under certain operating conditions, and an electric field strength of 1700 V/m can be obtained in the gel chamber. • Electrochromatography in a transverse electric field was mathematically modelled. • Use of a transverse electric field leads to less Joule heating than an axial field. • Scale-up electrochromatography was successfully performed using the model. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), an elderly neurodegenerative disorder with a high incidence and progressive memory decline, is one of the most expensive, lethal, and burdening diseases. To date, the pathogenesis of AD has not been fully illustrated. Emerging studies have revealed that cellular senescence and abnormal glucose metabolism in the brain are the early hallmarks of AD. Moreover, cellular senescence and glucose metabolism disturbance in the brain of AD patients may precede amyloid-β deposition or Tau protein phosphorylation. Thus, metabolic reprogramming targeting senescent microglia and astrocytes may be a novel strategy for AD intervention and treatment. Here, we recapitulate the relationships between neural cell senescence and abnormal glucose metabolism (e.g., insulin signaling, glucose and lactate metabolism) in AD. We then discuss the potential perspective of metabolic reprogramming towards an AD intervention, providing a theoretical basis for the further exploration of the pathogenesis of and therapeutic approach toward AD. [ABSTRACT FROM AUTHOR]

Extreme weather events are the common causes for power supply interruptions and power outages in electrical distribution systems. Improving the distribution system and enhancing its resilience is becoming crucial due to the increased frequency of extreme weather events. Preparation and allocation of multiple flexible resources, such as mobile resources, fuel resources, and labor resources before extreme weather events can mitigate the effects of extreme weather events and enhance the resilience of power distribution systems. In this paper, a two-stage stochastic mixed-integer linear programming (SMILP) is proposed to optimize the preparation and resource allocation process for upcoming extreme weather events, which leads to faster and more efficient post-event restoration. The objective of the proposed two-stage SMILP is to maximize the served load and minimize the operating cost of flexible resources. The first stage in the optimization problem selects the amounts and locations of different resources. The second stage considers the operational constraints of the distribution system and repair crew scheduling constraints. The proposed stochastic pre-event preparation model is solved by a scenario decomposition method, Progressive Hedging (PH), to ease the computational complexity introduced by a large number of scenarios. Furthermore, to show the impact of solar photovoltaic (PV) generation on system resilience, three types of PV systems are considered during a power outage and the resilience improvements with different PV penetration levels are compared. Numerical results from simulations on a large-scale (more than 10,000 nodes) distribution feeder have been used to validate the effectiveness and scalability of the proposed method. [Display omitted] • The power distribution systems are vulnerable to extreme weather events. • Pre-event preparation can enhance the resilience of the power distribution system. • A two-stage SMILP is proposed for pre-event preparation and resource allocation. • The impacts of PV generations on system resilience are fully considered. • To verify the scalability, a large-scale distribution feeder is tested. [ABSTRACT FROM AUTHOR]

• CREB binds to Nurr1 promoter constitutively in mouse ventral midbrain. • Restoration of CREB activity rescues Nurr1 downregulation induced by the parkinsonian toxin MPTP. • VP16-CREB shows prominent neuroprotective effect in parkinsonian mice. Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Nurr1 (NR4A2), a nuclear receptor essential for the maintenance of midbrain dopaminergic neurons, is transcriptionally downregulated in both patients with PD and animal models and has been considered as a promising therapeutic target for neuroprotection in PD. However, the mechanism underlying Nurr1 downregulation during dopaminergic degeneration has not been fully elucidated. Here, we report that the pro-survival transcription factor CREB is constitutively bound to the Nurr1 promoter in the mouse SN. CREB inactivation by dephosphorylation at Ser133 occurred in parallel with Nurr1 downregulation in the MPTP mouse model of PD. Forced expression of VP16-CREB, a constitutively active mutant, rescued Nurr1 expression and showed prominent neuroprotection in MPTP-intoxicated mice. Collectively, our results demonstrate that Nurr1 downregulation in the MPTP-induced PD mouse model is caused by CREB inactivation, which may provide a new target for neuroprotective therapy in PD. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence demonstrates that lncRNAs play pivotal roles in tumor energy metabolism; however, the detailed mechanisms of lncRNAs in the regulation of tumor glycolysis remain largely unknown. Methods: The expression of SLC2A1-AS1 was investigated by TCGA, GEO dataset and qRT-PCR. The binding of GLI3 to SLC2A1-AS1 promoter was detected by Luciferase Reporter Assay System and Ago2-RIP assay. FISH was performed to determine the localization of SLC2A1-AS1 in ESCC cells. Double Luciferase Report assay was used to investigate the interaction of miR-378a-3p with SLC2A1-AS1 and Glut1. Gain-of-function and Loss-of-function assay were performed to dissect the function of SLC2A1-AS1/miR-378a-3p/Glut1 axis in ESCC progression in vitro and in vivo. Results: We identified a novel lncRNA SLC2A1-AS1 in ESCC. SLC2A1-AS1 was frequently overexpressed in ESCC tissues and cells, and its overexpression was associated with TNM stage, lymph node metastasis and poor prognosis of ESCC patients. Importantly, GLI3 and SLC2A1-AS1 formed a regulatory feedback loop in ESCC cells. SLC2A1-AS1 promoted cell growth in vitro and in vivo, migration and invasion, and suppressed apoptosis, leading to EMT progression and increased glycolysis in ESCC cells. SLC2A1-AS1 functioned as ceRNA for sponging miR-378a-3p, resulting in Glut1 overexpression in ESCC cells. MiR-378a-3p inhibited cell proliferation and invasion as well as induced apoptosis, resulting in reduced glycolysis, which was partly reversed by SLC2A1-AS1 or Glut1 overexpression in ESCC cells. Conclusion: SLC2A1-AS1 plays important roles in ESCC development and progression by regulating glycolysis, and SLC2A1-AS1/miR-378a-3p/Glut1 regulatory axis may be a novel therapeutic target in terms of metabolic remodeling of ESCC patients. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence demonstrates that lncRNAs play pivotal roles in tumor energy metabolism; however, the detailed mechanisms of lncRNAs in the regulation of tumor glycolysis remain largely unknown. Methods: The expression of SLC2A1-AS1 was investigated by TCGA, GEO dataset and qRT-PCR. The binding of GLI3 to SLC2A1-AS1 promoter was detected by Luciferase Reporter Assay System and Ago2-RIP assay. FISH was performed to determine the localization of SLC2A1-AS1 in ESCC cells. Double Luciferase Report assay was used to investigate the interaction of miR-378a-3p with SLC2A1-AS1 and Glut1. Gain-of-function and Loss-of-function assay were performed to dissect the function of SLC2A1-AS1/miR-378a-3p/Glut1 axis in ESCC progression in vitro and in vivo. Results: We identified a novel lncRNA SLC2A1-AS1 in ESCC. SLC2A1-AS1 was frequently overexpressed in ESCC tissues and cells, and its overexpression was associated with TNM stage, lymph node metastasis and poor prognosis of ESCC patients. Importantly, GLI3 and SLC2A1-AS1 formed a regulatory feedback loop in ESCC cells. SLC2A1-AS1 promoted cell growth in vitro and in vivo, migration and invasion, and suppressed apoptosis, leading to EMT progression and increased glycolysis in ESCC cells. SLC2A1-AS1 functioned as ceRNA for sponging miR-378a-3p, resulting in Glut1 overexpression in ESCC cells. MiR-378a-3p inhibited cell proliferation and invasion as well as induced apoptosis, resulting in reduced glycolysis, which was partly reversed by SLC2A1-AS1 or Glut1 overexpression in ESCC cells. Conclusion: SLC2A1-AS1 plays important roles in ESCC development and progression by regulating glycolysis, and SLC2A1-AS1/miR-378a-3p/Glut1 regulatory axis may be a novel therapeutic target in terms of metabolic remodeling of ESCC patients. [ABSTRACT FROM AUTHOR]

2 rhMG53 lessens H2O2-induced oxidative injury to hUC-MSCs and promotes cell migration. a Representative images of hUC-MSCs with and without 200 M H2O2 treatment. b Time- and dose-dependent effects of H2O2 on hUC-MSCs. Two hundred micromolar H2O2 was used for subsequent experiments to induce hUC-MSC oxidative damage. c Dose-dependent effects of MG53 on hUC-MSCs. [Extracted from the article]

Traumatic brain injury (TBI) is one of the most devastating nervous injuries. Neural tissue engineering based on stem cells and bioactive scaffold is a promising but challenging approach for neural repair. A cutting-edge system with capability to control the fate of encapsulated stem cells is attractive to enhance neural regeneration after TBI. Herein, an injectable gelatin hydrogel dual-enzymatically cross-linked by horse radish peroxidase (HRP) and choline oxidase (ChOx) was performed as the neural scaffold to load murine bone marrow-derived mesenchymal stem cells (BMSC) for TBI treatment. The results of in vitro cellular experiments showed that low cross-linked gelatin hydrogel could obviously promote cellular viability, neural differentiation, and neurotrophins secretion of the loaded BMSC. In vivo tests on a TBI model of C57BL/6 mouse demonstrated that BMSC-laden gelatin hydrogel implants could significantly reduce the damaged area, ameliorate inflammation, attenuate neuronal apoptosis, facilitate survival and proliferation of endogenous neural cells, and promote the neurological function recovery of TBI mice. All data suggest that establishment of this three-dimensional (3D) gelatin hydrogel stem cell-loaded system is a promising therapeutic strategy for TBI or other neurological rehabilitation. [Display omitted] • An injectable and dual-enzymatically cross-linked gelatin hydrogel was used to load BMSC for TBI treatment • Low cross-linked gelatin hydrogel obviously enhances cellular viability, neural differentiation, and neurotrophin secretion • This GH/MSC hydrogel implantation could promote the neurogenesis and functional reconstruction of TBI mice [ABSTRACT FROM AUTHOR]

Background: Emerging evidence demonstrates that lncRNAs play pivotal roles in tumor energy metabolism; however, the detailed mechanisms of lncRNAs in the regulation of tumor glycolysis remain largely unknown. Methods: The expression of SLC2A1-AS1 was investigated by TCGA, GEO dataset and qRT-PCR. The binding of GLI3 to SLC2A1-AS1 promoter was detected by Luciferase Reporter Assay System and Ago2-RIP assay. FISH was performed to determine the localization of SLC2A1-AS1 in ESCC cells. Double Luciferase Report assay was used to investigate the interaction of miR-378a-3p with SLC2A1-AS1 and Glut1. Gain-of-function and Loss-of-function assay were performed to dissect the function of SLC2A1-AS1/miR-378a-3p/Glut1 axis in ESCC progression in vitro and in vivo. Results: We identified a novel lncRNA SLC2A1-AS1 in ESCC. SLC2A1-AS1 was frequently overexpressed in ESCC tissues and cells, and its overexpression was associated with TNM stage, lymph node metastasis and poor prognosis of ESCC patients. Importantly, GLI3 and SLC2A1-AS1 formed a regulatory feedback loop in ESCC cells. SLC2A1-AS1 promoted cell growth in vitro and in vivo, migration and invasion, and suppressed apoptosis, leading to EMT progression and increased glycolysis in ESCC cells. SLC2A1-AS1 functioned as ceRNA for sponging miR-378a-3p, resulting in Glut1 overexpression in ESCC cells. MiR-378a-3p inhibited cell proliferation and invasion as well as induced apoptosis, resulting in reduced glycolysis, which was partly reversed by SLC2A1-AS1 or Glut1 overexpression in ESCC cells. Conclusion: SLC2A1-AS1 plays important roles in ESCC development and progression by regulating glycolysis, and SLC2A1-AS1/miR-378a-3p/Glut1 regulatory axis may be a novel therapeutic target in terms of metabolic remodeling of ESCC patients. [ABSTRACT FROM AUTHOR]

Background: Atractylodes chinensis (DC.) Koidz is a well-known medicinal plant containing the major bioactive compound, atractylodin, a sesquiterpenoid. High-performance liquid chromatography (HPLC) analysis demonstrated that atractylodin was most abundant in 3-year old A. chinensis rhizome, compared with those from 1- and 2-year old rhizomes, however, the molecular mechanisms underlying accumulation of atractylodin in rhizomes are poorly understood. Results: In this study, we characterized the transcriptomes from rhizomes of 1-, 2- and 3-year old (Y1, Y2 and Y3, respectively) A. chinensis, to identify differentially expressed genes (DEGs). We identified 240, 169 and 131 unigenes encoding the enzyme genes in the mevalonate (MVA), methylerythritol phosphate (MEP), sesquiterpenoid and triterpenoid biosynthetic pathways, respectively. To confirm the reliability of the RNA sequencing analysis, eleven key gene encoding factors involved in the sesquiterpenoid and triterpenoid biosynthetic pathway, as well as in pigment, amino acid, hormone and transcription factor functions, were selected for quantitative real time PCR (qRT-PCR) analysis. The results demonstrated similar expression patterns to those determined by RNA sequencing, with a Pearson's correlation coefficient of 0.9 between qRT-PCR and RNA-seq data. Differential gene expression analysis of rhizomes from different ages revealed 52 genes related to sesquiterpenoid and triterpenoid biosynthesis. Among these, seven DEGs were identified in Y1 vs Y2, Y1 vs Y3 and Y2 vs Y3, of which five encoded four key enzymes, squalene/phytoene synthase (SS), squalene-hopene cyclase (SHC), squalene epoxidase (SE) and dammarenediol II synthase (DS). These four enzymes directly related to squalene biosynthesis and subsequent catalytic action. To validate the result of these seven DEGs, qRT-PCR was performed and indicated most of them displayed lower relative expression in 3-year old rhizome, similar to transcriptomic analysis. Conclusion: The enzymes SS, SHC, SE and DS down-regulated expression in 3-year old rhizome. This data corresponded to the higher content of sesquiterpenoid in 3-year old rhizome, and confirmed by qRT-PCR. The results of comparative transcriptome analysis and identified key enzyme genes laid a solid foundation for investigation of production sesquiterpenoid in A. chinensis. [ABSTRACT FROM AUTHOR]

Kidney renal clear cell carcinoma (KIRC) is a common malignant tumor in human genitourinary system. Previous studies have shown that the homeobox‐D (HOXD) cluster genes, which belong to the homeobox (HOX) family, are involved in the progression of multiple types of cancer. However, the expression profile and prognostic values of the HOXD genes in KIRC remain largely unknown. Herein, we comprehensively analyzed the transcriptional levels and prognosis of HOXD genes in KIRC using four online The Cancer Genome Atlas analysis databases (GEPIA, UALCAN, starBase v3.0, and LinkedOmics). We found that several members of the HOXD gene family were abnormally expressed in KIRC and correlated with patient prognosis. The messenger RNA levels of HOXD1, HOXD8, and HOXD10 were significantly downregulated in KIRC tissues as compared with the normal tissues. Low expression of HOXD1 or HOXD8 predicted poor overall survival (OS) of KIRC patients, and downregulated HOXD1, HOXD3, or HOXD4 indicated unfavorable patient disease‐free survival (DFS) in KIRC. Through integrated analysis, we found that HOXD1 was lowly expressed in KIRC and correlated with patient OS, DFS and advanced tumor stages. Moreover, gene set enrichment analysis showed that HOXD1 may be mainly implicated in cell cycle regulation, tumor growth factor‐β (TGF‐β) and Wnt signaling pathways in KIRC. Furthermore, both loss‐of‐function and gain‐of‐function experiments demonstrated that HOXD1 inhibited cell proliferation, cell cycle and the TGF‐β signaling in KIRC. Taken together, our findings suggest that HOXD1 is a novel potential tumor suppressor in KIRC. [ABSTRACT FROM AUTHOR]

Stem cell transplantation is a promising therapy for wound healing, but the low retention and survival of transplanted stem cells limit their application. Injectable hydrogels exert beneficial effects in skin tissue engineering. In this study, an injectable hydrogel composed of sodium alginate (SA) and collagen type I (Col) was synthesized as a tissue scaffold to improve the efficacy of stem cells in a full-thickness excision wound model. Our results showed that SA/Col hydrogel was injectable, biodegradable, and exhibited low immunogenicity, which could promote the retention and survival of hUC-MSCs in vivo. SA/Col loaded with hUC-MSCs showed reduced wound size (p < 0.05). Histological and immunofluorescence results confirmed that SA/Col loaded with hUC-MSCs significantly promoted the formation of granulation, enhanced collagen deposition and angiogenesis, increased VEGF and TGF-β1 expression (p < 0.05), and mitigated inflammation evidenced by lower production of TNF-α and IL-1β and higher release of IL-4 and IL-10 (p < 0.05). Furthermore, SA/Col loaded with hUC-MSCs significantly lowered the expression of NLRP3 inflammasome-related proteins (p < 0.05). Taken together, our results suggest that SA/Col loaded with hUC-MSCs promotes skin wound healing via partly inhibiting NLRP3 pathway, which has potential to the treatment of skin wounds. [ABSTRACT FROM AUTHOR]

[Display omitted] • Bomidin is a new recombinant antimicrobial peptide AMP derived from BMAP-27. • Bomidin mediates Keap1 protein degradation, enhancing Nrf2 nuclear translocation. • Bomidin can suppress ferroptosis, further relieving periodontitis. • Bomidin is a promising medicine for periodontitis. Periodontitis is a prevalent oral immunoinflammatory condition that is distinguished by the compromised functionality of periodontal ligament stem cells (PDLSCs). Bomidin, a new recombinant antimicrobial peptide (AMP), exhibits antibacterial properties and modulates immune responses. Nevertheless, the precise anti-inflammatory impact of bomidin in periodontitis has yet to be fully elucidated. Thus, the study aimed to clarified the role of bomidin in modulating inflammation and its underlying mechanisms. TNF-α was applied to treating PDLSCs for establishing a cell model of periodontitis. Bomidin, RSL3, ML385 and cycloheximide were also used to treat PDLSCs. Transcriptome sequencing, RT-qPCR, western blot, immunofluorescence, immunohistochemistry, Fe2+ detection probe, molecular docking, Co-IP assay, ubiquitination assay and murine models of periodontitis were used. Our study demonstrated that bomidin effectively suppressed inflammation in PDLSCs stimulated by TNF-α, through down-regulating the MAPK and NF-κB signaling pathways. Furthermore, bomidin exerted inhibitory effects on ferroptosis and activated the Keap1/Nrf2 pathway in the TNF-α group. There is a strong likelihood of bonding bomidin with Keap1 protein, which facilitated the degradation of Keap1 protein via the ubiquitin–proteasome pathway, leading to an enhanced translocation of Nrf2 protein to the nucleus. Bomidin can directly bond to Keap1 protein, resulting in the degradation of Keap1 through the ubiquitin–proteasome pathway, thereby further activating the Keap1/Nrf2 pathway. The upregulation of the Keap1/Nrf2 signaling pathway was found to contribute to the suppression of ferroptosis, ultimately alleviating inflammation in treatment of periodontitis. [ABSTRACT FROM AUTHOR]