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Tin selenide materials have attracted much attention due to the intrinsic low thermal conductivity. However, the further application of SnSe materials is limited due to the poor electrical conductivity. Herein, a two-step doping process is employed on p-type polycrystalline SnSe materials to enhance the thermoelectric properties. It is found that the Sn0·98Ag0.01Ga0.01Se sample achieves a high ZT value of 1.53 at 823 K and a quite competitive ZTave value of 1.04 from 673 to 823 K. This is attributed to the associations of point defects, AgSn′, GaSn·, and Ga0, and nano-precipitates, SnGa4Se7, Ag9GaSe6 and AgGa1+δ. In those defects, AgSn′ acts as an accepter, which can conduce to enhancing the hole carrier concentration. Ga element doping astonishingly play dual-roles, in that it both faultlessly maintains the electrical transport properties and effectively decreases the thermal conductivity through the associations with the point defects, GaSn·, and Ga0, and nano-precipitates, SnGa4Se7, Ag9GaSe6 and AgGa1+δ. The method paves the way for achieving high thermoelectric properties in SnSe materials by the point defects engineering and nano-precipitates.

Tri-allelic pattern in autosomal STR is a common abnormal typing phenomenon in forensic DNA analysis, which brings difficulties and uncertainties to the evaluation of the evidence weight in actual cases. This paper reviews the types, formation mechanism, occurrence frequency, genetic pattern and quantitative evaluation of evidence of the tri-allelic pattern in autosomal STR in forensic DNA analysis. This paper mainly explains the formation mechanism and genetic patterns based on different types of tri-allelic pattern. This paper also discusses the determination of tri-allelic pattern and the quantitative method of evidence evaluation in paternity testing and individual identification. This paper aims to provide references for scientific and standardized analysis of this abnormal typing phenomenon in forensic DNA analysis.

Targeted therapy has been standardized in front-line therapies for metastatic colorectal cancer (mCRC), while explicit recommendations for third- or later-line are still lacking. This study evaluated the efficacy and safety of combining targeted therapy with chemotherapy in the third- or later-line treatment for mCRC via meta-analysis, providing evidence-based guidance for clinical or research practice. Comprehensive retrieval of related studies was conducted according to the PRISMA guideline. Studies were stratified with patient characteristics and pharmacological classification of the drugs. For the data available for quantitative analysis, pooled overall response rate, disease control rate, hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and adverse events rate with respective 95% confidence intervals (CIs) were calculated. A total of 22 studies (1,866 patients) were included in this meta-analysis. Data from 17 studies (1,769 patients) involving targets of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) were extracted for meta-analyses. The overall response rates for monotherapy and combined therapy were 4% (95% CI: 3%, 5%) and 20% (95% CI: 11%, 29%). The pooled HRs (combined therapy vs. mono) for OS and PFS were 0.72 (95% CI: 0.53, 0.99) and 0.34 (95% CI: 0.26, 0.45). Another five studies were included in narrative depiction, involving targets of BRAF, HER-2, ROS1, and NTRK. The findings of this meta-analysis indicate that VEGF and EGFR inhibitors manifest promising clinical response rates and prolonged survival in the treatment of mCRC with acceptable adverse events.

Abstract Background Immune checkpoint inhibitors had a great effect in triple-negative breast cancer (TNBC); however, they benefited only a subset of patients, underscoring the need to co-target alternative pathways and select optimal patients. Herein, we investigated patient subpopulations more likely to benefit from immunotherapy and inform more effective combination regimens for TNBC patients. Methods We conducted exploratory analyses in the FUSCC cohort to characterize a novel patient selection method and actionable targets for TNBC immunotherapy. We investigated this in vivo and launched a phase 2 trial to assess the clinical value of such criteria and combination regimen. Furthermore, we collected clinicopathological and next-generation sequencing data to illustrate biomarkers for patient outcomes. Results CD8-positivity could identify an immunomodulatory subpopulation of TNBCs with higher possibilities to benefit from immunotherapy, and angiogenesis was an actionable target to facilitate checkpoint blockade. We conducted the phase II FUTURE-C-Plus trial to assess the feasibility of combining famitinib (an angiogenesis inhibitor), camrelizumab (a PD-1 monoclonal antibody) and chemotherapy in advanced immunomodulatory TNBC patients. Within 48 enrolled patients, the objective response rate was 81.3% (95% CI, 70.2–92.3), and the median progression-free survival was 13.6 months (95% CI, 8.4–18.8). No treatment-related deaths were reported. Patients with CD8- and/or PD-L1- positive tumors benefit more from this regimen. PKD1 somatic mutation indicates worse progression-free and overall survival. Conclusion This study confirms the efficacy and safety of the triplet regimen in immunomodulatory TNBC and reveals the potential of combining CD8, PD-L1 and somatic mutations to guide clinical decision-making and treatments. Trial registration ClinicalTrials.gov: NCT04129996 . Registered 11 October 2019.

Abstract Background Multiple myeloma (MM) is a hematologic malignancy characterized by the accumulation of aberrant plasma cells within the bone marrow. The high frequent mutation of family with sequence similarity 46, member C (FAM46C) is closely related with the occurrence and progression of MM. Recently, FAM46C has been identified as a non‐canonical poly(A) polymerase (PAP) that functions as a tumor suppressor in MM. This study aimed to elucidate the structural features of this novel non‐canonical PAP and how MM‐related mutations affect the structural and biochemical properties of FAM46C, eventually advancing our understandings towards FAM46C mutation‐related MM occurrence. Methods We purified and crystallized a mammalian FAM46C construct, and solved its structure. Next, we characterized the property of FAM46C as a PAP through a combination of structural analysis, site‐directed mutagenesis and biochemical assays, and by comparison with its homolog FAM46B. Finally, we structurally analyzed MM‐related FAM46C mutations and tested the enzymatic activity of corresponding mutants. Results We determined the crystal structure of a mammalian FAM46C protein at 2.35 Å, and confirmed that FAM46C preferentially consumed adenosine triphosphate (ATP) and extended A‐rich RNA substrates. FAM46C showed a weaker PAP activity than its homolog FAM46B, and this difference was largely dependent on the residue variance at particular sites. Of them, residues at positions 77, 290, and 298 of mouse FAM46C were most important for the divergence in enzymatic activity. Among the MM‐associated FAM46C mutants, those residing at the catalytic site (D90G and D90H) or putative RNA‐binding site (I155L, S156F, D182Y, F184L, Y247V, and M270V) showed abolished or compromised PAP activity of FAM46C, while N72A and S248A did not severely affect the PAP activity. FAM46C mutants D90G, D90H, I155L, S156F, F184L, Y247V, and M270V had significantly lower inhibitory effect on apoptosis of RPMI‐8226 cells as compared to wild‐type FAM46C. Conclusions FAM46C is a prokaryotic‐like PAP with preference for A‐rich RNA substrates, and showed distinct enzymatic efficiency with its homolog FAM46B. The MM‐related missense mutations of FAM46C lead to various structural and biochemical outcomes to the protein.

ObjectiveDelayed enhancement cardiac CT is a reliable tool for the diagnosis of left atrial appendage thrombus but limited for scanning heterogeneity. We aimed to explore the improvement of the 1 and 3-min delay phase at the diagnostic level to detect left atrial appendage thrombus, in order to set up a reasonable CT scanning scheme.Materials and MethodsA total of 6,524 patients were continuously retrieved from January 2015 to September 2020 retrospectively. The patients had undergone Transesophageal echocardiography (TEE) and cardiac CT with complete period include the arterial enhancement phase, 1 and 3-min delay phase, TEE were used as the reference standard. The final study included 329 patients. Three experienced radiologists independently assessed each phase of the cardiac CT images for thrombus diagnosis. We explored the improvement of the diagnostic ability of different delayed contrast-enhanced phases for left atrial appendage thrombus detection. Multiple logistic regression analysis were used for further high-risk stratification to avoid an additional 1-min delayed scan.ResultsIn total, 29 thrombosis were detected at TEE. For all cardiac CT phases, sensitivity and negative predictive were 100%. The specificity were 0.54, 0.93, and 1.00, respectively; The positive predictive values (PPV) were 0.17, 0.57, and 1.00, respectively; Area under curve (AUC) were 0.75, 0.95, and 0.98, respectively. High risk factors that cannot be clearly diagnosed with 1-min delay phase included reduced cardiac function, increased CHA2DS2-VAScscore and left atrial enlargement. Compared with the arterial enhanced phase, increased radiation doses in the 1 and 3-min delay phases were 1.7 ± 1.3 msv and 1.5 ± 0.8 msv (mean ± standard deviation).ConclusionUsing TEE as the reference standard, early contrast-enhanced CT scanning with 1 and 3-min delay is necessary for the diagnosis of left appendage thrombus, which could significantly improve the diagnostic efficiency. Patients with high-risk stratification are suitable for direct 3-min delayed scanning.

From the rice fermentation product of a new record fungus, Neohelicosporium griseum, two new polyketides, neogrisphenol A (1) and neogrisphenol B (2), one new isochroman-1-one, (S)-6-hydroxy-7-methoxy-3,5-dimethylisochroman-1-one (3), and four known compounds (4–7) were isolated. Their structures were determined using 1D- and 2D-NMR, mass spectrometry, and chemical calculations. The C-3~C-2′ polymerization mode between the two α-naphthalenone derivative moieties is uncommon in compounds 1 and 2. Meanwhile, compounds 1–2 and 5 exhibited antibacterial activity against Bacillus subtilis, Clostridium perfringens, Staphylococcus aureus, and Staphylococcus aureus, with MIC values ranging between 16 and 31 µg/mL. In addition, compound 5 showed antifungal activity against Sclerotinia sclerotiorum and Phytophthora nicotianae var. nicotianae, with respective IC50 values of 88.14 ± 2.21 µg/mL and 52.36 ± 1.38 µg/mL. Compound 1 showed significant cytotoxicity against A2780, PC-3, and MBA-MD-231 cell lines with respective IC50 values of 3.20, 10.68, and 16.30 µM, and the cytotoxicity against A2780 cells was even higher than that of cisplatin (CDDP). With an IC50 value of 10.13 µM, compound 2 also exhibited cytotoxicity against A2780. The in vitro results showed that compound 1 inhibited A2780 cell proliferation, induced apoptosis, and arrested the cell cycle at the S-phase in a concentration-dependent manner.

Using standard DNA-damaging medicines with DNA repair inhibitors is a promising anticancer tool to achieve better therapeutic responses and reduce therapy-related side effects. Cell viability assay, neutral comet assay, western blotting (WB), and cell cycle and apoptosis analysis were used to determine the synergistic effect and mechanism of ML216, a Bloom syndrome protein (BLM) helicase inhibitor, and cisplatin (CDDP), a DNA-crosslinking agent, in PCa cells. Based on the online database research, our findings revealed that BLM was substantially expressed in PCa, which is associated with a bad prognosis for PCa patients. The combination of ML216 and CDDP improved the antiproliferative properties of three PCa cell lines. As indicated by the increased production of γH2AX and caspase-3 cleavage, ML216 significantly reduced the DNA damage-induced high expression of BLM, making PC3 more susceptible to apoptosis and DNA damage caused by CDDP. Furthermore, the combination of ML216 and CDDP increased p-Chk1 and p-Chk2 expression. The DNA damage may have triggered the ATR-Chk1 and ATM-Chk2 pathways simultaneously. Our results demonstrated that ML216 and CDDP combination therapy exhibited synergistic effects, and combination chemotherapy could be a novel anticancer tactic.

ObjectiveMesenchymal stromal cell–derived exosomes have been applied for the treatment of several immune diseases. This study aimed to explore the effect of human bone marrow–derived mesenchymal stem cell (hBMSC)–derived exosomes on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT).MethodshBMSC were cultured, and the culture supernatants were then collected to prepare exosomes using total exosome isolation reagent from Invitrogen. Mouse aGVHD model was established by allogeneic cell transplantation and injected with hBMSC-derived exosomes (Msc-exo) via tail vein. Exosomes from human fibroblast (Fib-exo) were used as the treatment control. The effects of Msc-exo on dendritic cells, CD4+, and CD8+ T cells in aGVHD mice were analyzed through flow cytometry. The impact on inflammatory cytokines was tested by ELISA. Besides, the body weight, survival rate, and clinical score of treated mice were monitored.ResultsMsc-exo were successfully prepared. aGVHD mice injected with Msc-exo led to 7–8-fold increase of the CD8α+ conventional dendritic cells (cDCs) and CD11b+ cDCs compared with the controls. In addition, Msc-exo altered the T help and Treg subpopulation, and decreased the cytotoxicity and proliferation of cytotoxic T cells to favor inflammatory inhibition in aGVHD mice. Mice that received Msc-exo exhibited decreased weight loss and reduced aGVHD clinical score in a time-dependent manner as well as reduced lethality compared with Fib-exo treated or untreated control. Furthermore, the levels of IL-2, TNF-α, and IFN-γ were decreased, as well as the level of IL-10 was increased after Msc-exo treatment in vivo and in vitro.ConclusionhBMSC-derived exosomes could attenuate aGVHD damage and promote the survival of aGVHD mice by regulating the DC and T-cell subpopulation and function, and lead to inhibited inflammatory response in aGVHD mice.

Abstract We generalize several monotonicity and convexity properties as well as sharp inequalities for the complete elliptic integrals to the complete p-elliptic integrals.

Abstract We provide several sharp upper and lower bounds for the generalized Euler–Mascheroni constant. As consequences, some previous bounds for the Euler–Mascheroni constant are improved.

Abstract: Field studies were conducted in 2012 and 2013 to evaluate weed and insect control efficacy with glyphosate at 1 230 g ai (active ingredient) ha−1 and the insecticides acephate (728 g ai ha−1), carbosulfan (135 g ai ha−1), endosulfan (683 g ai ha−1), imidacloprid (32 g ai ha−1), or lambda-cyhalothrin (23 g ai ha−1), as well as glyphosate tank-mixed with these insecticides. Four of the most common weeds in cotton, common purslane, false daisy, goosegrass, and lambsquarters, were manually sown in the cotton field and treated with glyphosate alone or in combination with insecticides. Glyphosate efficacy, based on visual estimates of control and weed fresh weight at 21 d after treatment (DAT), was unaffected by the addition of insecticides. Four weeds were controlled by 93–97% and 86–100% (visual rating) and reduced weed fresh biomass by 98–99% and 96–100% with glyphosate alone and its combination with insecticides, respectively. Addition of glyphosate to acephate improved cotton aphid control compared with acephate alone. However, addition of glyphosate to carbosulfan, endosulfan, imidacloprid, or lambda-cyhalothrin did not affect the aphid control when compared with the insecticide alone treatments. These results indicate that cotton producers could potentially integrate weed and insect management strategies by choosing suitable insecticide mixing partners with glyphosate, thereby reducing the application costs without sacrificing the efficacy of the glyphosate or the insecticides.

Background: This study aimed to observe the differences in brain gray matter volume in drug-naive female patients after the first episode of major depression with and without stressful life events (SLEs) before the onset of depression. Methods: Forty-three drug-naive female patients voluntarily participated in the present study after the first major depressive episode. The life event scale was used to evaluate the severity of the impact of SLEs during 6 months before the onset of the major depressive episode. High-field magnetic resonance imaging (MRI) scans were obtained, and the VBM and SPM8 software process were used to process and analyze the MRI. Results: Compared to that in patients without SLEs, the volume of brain gray matter was lower in the bilateral temporal lobe, right occipital lobe, and right limbic lobe in the SLE group. However, the gray matter volume did not differ significantly between the two groups after the application of false discovery rate (FDR) correction. Conclusions: Although the results of the present study suggest the absence of significant differences in brain gray matter volume between female drug-naive patients after the first episode of major depression with and without SLEs after FDR correction, the study provides useful information for exploring the definitive role of stress in the onset of depression.

Goosegrass is one of the worst agricultural weeds on a worldwide basis. Understanding of its interference impact in crop field will provide useful information for weed control programs. Field experiments were conducted during 2010–2012 to determine the influence of goosegrass density on cotton growth at the weed densities of 0, 0.125, 0.25, 0.5, 1, 2, and 4 plants m−1 of row. Seed cotton yield tended to decrease with the increase in weed density, and goosegrass at a density of 4 plants m−1 of row significantly reduced cotton yields by 20 to 27%. A density of 11.6–19.2 goosegrass plant m−1 of row would result in a 50% cotton yield loss from the maximum yield according to the hyperbolic decay regression model. Boll production was not affected in the early growing season. But boll numbers per plant were reduced about 25% at the density of 4 plants m−1 of row in the late growing season. Both cotton boll weight and seed numbers per boll were significantly reduced (8%) at 4 goosegrass plants m−1 of row. Cotton plant height, stem diameter and sympodial branch number were not affected as much as cotton yields by goosegrass competition. Seed index, lint percentage and lint fiber properties were unaffected by weed competition. Intraspecific competition resulted in density-dependent effects on weed biomass per plant, 142–387 g dry weight by harvest. Goosegrass biomass m−2 tended to increase with increasing weed density as indicated by a quadratic response. The adverse impact of goosegrass on cotton yield identified in this study has indicated the need of effective goosegrass management.

According to the problem that conventional imaging algorithms have some unavoidable shortcomings such as low resolution of image and being fragile to the noise with short coherent processing interval (CPI),an improved ISAR imaging algorithm via CS method,namely,PH-SL0 algorithm,was proposed.In the proposed algorithm,as a kind of measure matrix,partial randomizer Hadamard matrix (PH) has many advantages such as high reconstruction precision and low dimension of measure matrix.Meanwhile,as a reconstruction algorithm,SL0 has many advantages such as demanding fewer measurements than existing methods,having higher reconstructed accuracy and better robust.Therefore,making use of the advantages of PH and SL0,and extending them to the field of radar,the azimuth imaging with short imaging data could be implemented.Finally,simulation results and experimental results of real data show that the algorithm has higher imaging resolution and better robust to noise.

As a candidate for bioherbicide, 4,8-dihydroxy-1-tetralone (4,8-DHT) was isolated from Caryospora callicarpa epicarp and its two enantiomers, S-(+)-isosclerone and R-(−)-regiolone, were separated by chiral high-performance liquid chromatography (HPLC) on a Chiralcel OD column with chiral stationary phase (CSP)-coated cellulose-tris(3,5-dimethylphenylcarbamate). Then, the phytotoxicity of 4,8-DHT and its enantiomers toward the seeds germination and seedling growth of the five tested plant species, including lettuce (Latuca sativa), radish (Raphanus sativus), cucumber (Cucumis sativus), onion (Allium cepa), and wheat (Triticum aestivum), were investigated and the results indicated a hormesis at low concentration of 4,8-DHT and its enantiomers, but a retardant effect at high concentration. Between the two enantiomers of 4,8-DHT, the S-(+)-isosclerone was more toxic to seeds germination and seedling growth of the five tested plant species than the R-(−)-regiolone, and also the phytotoxicity of S-(+)-isosclerone varied with different plants. For example, S-(+)-isosclerone was the most active to seedling growth of lettuce, indicating that S-(+)-isosclerone had specific effects on different organisms. Thus, all of the chirality and concentration of 4,8-DHT, as well as the affected plant species, need to be taken into consideration in the development and utilization of 4,8-DHT.

In the title compound, C18H19NO2, the five-membered ring of the indane fragment adopts an envelope conformation with the unsubstituted carbon atom at the flap displaced by 0.412 (3) Å from the plane formed by the other four atoms. The nitro group forms a dihedral angle of 5.3 (2)° with the indane benzene ring while the dihedral angle between the phenyl ring and the indane benzene ring is 76.74 (9)°.

In the molecule of the title compound, C25H20N2O3, the dihedral angles formed by adjacent benzene rings are 66.75 (8), 48.37 (8) and 71.43 (9)°. In the crystal structure, centrosymmetrically related molecules are linked into dimers by intermolecular N—H...O hydrogen bonds.

The title compound, C16H8O3, was synthesized by the Pd-coupling reaction of phenylacetylene with 4-bromophthalic anhydride. The phenyl and isobenzofurane rings are nearly coplanar, forming a dihedral angle of 6.70 (10)°. In the crystal structure, centrosymmetrically related molecules are linked into dimers by C—H...O hydrogen bonds.

The asymmetric unit of the title compound, C20H18O8, contains two molecules with small geometric differences. The dihedral angles between the benzene rings are 62.94 (12) and 59.99 (12)°. The dihedral angles between the carboxylate groups in the 2- and 3-positions are 81.72 (13) and 65.54 (15)°, respectively. However, the dihedral angles between the carboxylate groups in the 3′ and 4′-positions are 67.24 (15) and 59.98 (17)°, respectively.

In the title compound, C24H21NO2·C2H6O, the dihedral angle between the two aromatic ring systems is 87.00 (6)°. There is an intramolecular O—H...N hydrogen bond, which forms a six-membered ring. Intermolecular O—H...O hydrogen bonds stabilize the crystal structure.