Bis{μ-1,3-bis­[(2-methyl-1H-benzimid­azol-1-yl)meth­yl]benzene-κ2 N 3:N 3′}bis­(diiodidocadmium)

In the title compound, [Cd2I4(C24H22N4)2], the 1,3-bis­[(2-methyl-1H-benzimidazol-1-yl)meth­yl]benzene ligand bridges two CdI2 units, forming a centrosymmetric dinuclear complex. The CdII atom adopts a distorted tetra­hedral coordination geometry. In the crystal, complex mol­ecules are linked into columns parallel to [101] by π–π stacking inter­actions, with centroid–centroid distances of 3.558 (2) Å

Stochastic Weight Averaging Revisited

Averaging neural network weights sampled by a backbone stochastic gradient descent (SGD) is a simple yet effective approach to assist the backbone SGD in finding better optima, in terms of generalization. From a statistical perspective, weight averaging (WA) contributes to variance reduction. Recently, a well-established stochastic weight averaging (SWA) method is proposed, which is featured by the application of a cyclical or high constant (CHC) learning rate schedule (LRS) in generating weight samples for WA. Then a new insight on WA appears, which states that WA helps to discover wider optima and then leads to better generalization. We conduct extensive experimental studies for SWA, involving a dozen modern DNN model structures and a dozen benchmark open-source image, graph, and text datasets. We disentangle contributions of the WA operation and the CHC LRS for SWA, showing that the WA operation in SWA still contributes to variance reduction but does not always lead to wide optima. The experimental results indicate that there are global scale geometric structures in the DNN loss landscape. We then present an algorithm termed periodic SWA (PSWA) which makes use of a series of WA operations to discover the global geometric structures. PSWA outperforms its backbone SGD remarkably, providing experimental evidences for the existence of global geometric structures. Codes for reproducing the experimental results are available at https://github.com/ZJLAB-AMMI/PSWA

Post-marketing safety surveillance of sacituzumab govitecan: an observational, pharmacovigilance study leveraging FAERS database

Background and objective: Sacituzumab govitecan (SG), the first antibody-drug conjugate targeting human trophoblast cell-surface antigen 2 (Trop-2), has been approved by the Food and Drug Administration (FDA) for the treatment of advanced or metastatic breast cancer and urothelial cancer. However, there is currently a dearth of information regarding the safety profiles of SG in a large sample cohort. The objective of the present study is to investigate SG-related adverse events (AEs) in real-world settings leveraging the FDA Adverse Event Reporting System (FAERS) database to guide the safety management of clinical medication.Methods: The FAERS database was retrospectively queried to extract reports associated with SG from April 2020 to March 2023. To identify and evaluate potential AEs in patients receiving SG, various disproportionality analyses such as reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed.Results: Overall, 2069 reports of SG as the “primary suspect” were identified. Noteworthy, SG was significantly associated with an increased risk of blood lymphatic system disorders (ROR, 7.18; 95% CI, 6.58–7.84) and hepatobiliary disorders (ROR, 2.68; 95% CI, 2.17–3.30) at the System Organ Class (SOC) level. Meanwhile, 61 significant disproportionality preferred terms (PTs) simultaneously complied with all four algorithms were adopted. Therein, anemia, thrombocytopenia, neutropenia, leukopenia, diarrhea, asthenia, alopecia, and electrolyte imbalance were consistent with the common AEs described in the clinical trials and specification of SG. Furthermore, unexpected significant AEs include colitis (ROR, 12.09; 95% CI, 9.1–16.08), heart rate increased (ROR, 5.11; 95% CI, 3.84–6.79), sepsis (ROR, 4.77; 95% CI, 3.59–6.34), cholestasis (ROR, 6.28; 95% CI, 3.48–11.36), blood bilirubin increased (ROR, 4.65; 95% CI, 2.42–8.94) and meningitis (ROR, 7.23; 95% CI, 2.71–19.29) were also be detected. The median time to onset of SG-related AEs was 14 [interquartile range (IQR), 7–52] days, with the majority occurring within the initial month of SG treatment.Conclusion: Our study validates the commonly known AEs and also found some potentially emerging safety issues related to SG in real-world clinical practice, which could provide valuable vigilance evidence for clinicians and pharmacists to manage the safety issues of SG

Establishment of in Vitro Binding Assay of High Mobility Group Box-1 and S100A12 to Receptor for Advanced Glycation Endproducts: Heparin's Effect on Binding

Interaction between the receptor for advanced glycation end products (RAGE) and its ligands has been implicated in the pathogenesis of various inflammatory disorders. In this study, we establish an in vitro binding assay in which recombinant human high-mobility group box 1 (rhHMGB1) or recombinant human S100A12 (rhS100A12) immobilized on the microplate binds to recombinant soluble RAGE (rsRAGE). The rsRAGE binding to both rhHMGB1 and rhS100A12 was saturable and dependent on the immobilized ligands. The binding of rsRAGE to rhS100A12 depended on Ca2 and Zn2, whereas that to rhHMGB1 was not. Scatchard plot analysis showed that rsRAGE had higher affinity for rhHMGB1 than for rhS100A12. rsRAGE was demonstrated to bind to heparin, and rhS100A12, in the presence of Ca2, was also found to bind to heparin. We examined the effects of heparin preparations with different molecular sizesunfractionated native heparin (UFH), low molecular weight heparin (LMWH) 5000Da, and LMWH 3000Da on the binding of rsRAGE to rhHMGB1 and rhS100A12. All 3 preparations concentration-dependently inhibited the binding of rsRAGE to rhHMGB1 to a greater extent than did rhS100A12. These results suggested that heparin's anti-inflammatory effects can be partly explained by its blocking of the interaction between HMGB1 or S100A12 and RAGE. On the other hand, heparin would be a promising effective remedy against RAGE-related inflammatory disorders.</p

Naphthalene-2,6-dicarb­oxy­lic acid–1-methyl­pyrrolidin-2-one (1/2)

The asymmetric unit of the title compound, C12H8O4·2C5H9NO, contains one half-mol­ecule of naphthalene-2,6-dicarb­oxy­lic acid (NDA) and one mol­ecule of 1-methyl­pyrrolidin-2-one (NMP): the NDA molecules lie on the crystallographic twofold rotation axes. In the crystal, the components are linked by strong O—H⋯O hydrogen bonds and C—H⋯O inter­actions

High-resolution QTL mapping for grain appearance traits and co-localization of chalkiness-associated differentially expressed candidate genes in rice

Table S4. Annotated function of differentially expressed genes identified between parents. (XLSX 1232 kb

Petrogenesis of granitoids in the eastern section of the Central Qilian Block: Evidence from geochemistry and zircon U-Pb geochronology

The Caledonian-age Qilian Orogenic Belt at the northern margin of the Greater Tibetan Plateau comprises abundant granitoids that record the histories of the orogenesis. We report here our study of these granitoids from two localities. The Qingchengshan (QCS) pluton, which is situated in the eastern section of the Central Qilian Block, is dated at ~430–420 Ma. It has high-K calc-alkaline composition with high SiO2 (> 70 wt%), enrichment in large ion lithophile elements (LILEs), depletion in high field strength elements (HFSEs), and varying degrees of negative Sr and Eu anomalies. The granitoids in the Tongwei (TW) area, 150 km east of the QCS, are complex, the majority of which are dated at ~440 Ma, but there also exist younger, ~230 Ma intrusions genetically associated with the Qinling Orogeny. The Paleozoic TW intrusions also have high SiO2, fractionated REE (rare earth element) patterns, but a negligible Eu anomaly. The whole rock Sr-Nd-Hf isotopic compositions suggest that all these Paleozoic granitoids are consistent with melting-induced mixing of a two-component source, which is best interpreted as the combination of last fragments of subducted/subducting ocean crust with terrigenous sediments. The mantle isotopic signature of these granitoids (87Sr/86Sri: 0.7038 to 0.7100, εNd(t): −4.8 to −1.3, εHf(t): −0.7 to +4.0) reflects significant (~70 %) contribution of the ocean crust derived in no distant past from the mantle at ocean ridges with an inherited mantle isotopic signature. Partial melting of such ocean crust plus terrigenous sediments in response to the ocean closing and continental collision (between the Qilian and Alashan Blocks) under amphibolite facies conditions is responsible for the magmatism. Varying extents of fractional crystallization (±plagioclase, ±amphibole, ±garnet, ±zircon) of the parental magmas produced the observed QCS and TW granitoids. We note that sample HTC12–01 in the TW area shows an A-type or highly fractionated granite signature characterized by elevated abundances and a flat pattern of REEs, weak Nb-Ta anomaly, conspicuous negative Sr and Eu anomalies (Sr/Sr* = 0.09, Eu/Eu* = 0.22), and thus the high 87Sr/86Sr ratio (0.7851), and moderate εNd(t) (−4.9) and εHf(t) (−2.0), pointing to the significant mantle contribution. Compared with the Paleozoic granitoids, the ~230 Ma granitoids in the TW area represented by sample JPC12–02 have higher initial 87Sr/86Sr (0.7073) and lower εNd(t) (−6.2) and εHf(t) (−4.5) values, offering an ideal opportunity for future studies on tectonic effects of juxtaposition of younger orogenesis on an older orogen

Ventral Visual Pathway-Cerebellar Circuit Deficits in Alcohol Dependence: Long- and Short-Range Functional Connectivity Density Study

Objective: To identify the underlying intrinsic functional connectome changes in patients with alcohol dependence.Methods: A functional connectivity density (FCD) analysis was used to report on the functional connectivity changes in 24 male patients with alcohol dependence (age, 47.83 ± 6.93 years) and 24 healthy male subjects (age, 47.67 ± 6.99 years). We defined the voxels with a correlated threshold of r &gt; 0.25 inside their neighborhood (radius sphere ≤ 6 mm) as shortFCD, and radius sphere &gt; 6 mm as longFCD. We repeated the network analysis using a range of correlation r thresholds (r = 0.30, 0.35, 0.40, 0.45, 0.50, 0.6, and 0.75) to determine whether between-group differences were substantially affected by the selection of the different R-value thresholds used. A ROC curve was used to test the ability of the FCD in discriminating between the two groups. Pearson's correlation was used to evaluate the relationships between the FCD differences in brain areas and demographic characteristics.Results: The covered differences in brain areas in binarized shortFCD were larger than binarized longFCD in both groups. The intra-group FCD differences did not depend on the selection of different thresholds used. Patients with alcohol dependence were associated with the longFCD deficit in the cerebellum posterior lobe, and shortFCD deficit in the ventral system of the visual pathway and increased shortFCD in the left precentral gyrus, right salience network and right cingulate gyrus. A ROC curve demonstrated that these specific brain areas alone discriminated between the two groups with a high degree of sensitivity and specificity. In the alcohol dependence group, the cerebellum posterior lobe, visual association cortex and the salience network displayed significant correlations with demographic characteristics.Conclusions: The shortFCD analysis was more sensitive than the longFCD analysis in finding differences in the brain areas. The ventral visual pathway-cerebellar circuit deficit appeared to be altered in patients with alcohol dependence