Guest-guided anchoring patterns of cyclodextrin supramolecular microcrystals on droplet surfaces.

The growth of cyclodextrin inclusion complexes (ICs) on oil/water interfaces represents a beautiful example of spontaneous pattern formation in nature. How the supramolecules evolve remains a challenge because surface confinement can frustrate microcrystal growth and give rise to unusual phase transitions. Here we investigate the self-assembly of ICs on droplet surfaces using microfluidics, which allows directly visualizing packing, wetting and ordering of the microcrystals anchored on the surface. The oil guests of distinct molecular structures can direct the assembly of the ICs and largely affect anchoring dynamics of the ICs microcrystals, leading to a range of behaviors including orientating, slipping, buckling, jamming, or merging. We discuss the behaviors observed in terms of the flexibility of the building blocks, which offers a new degree of freedom through which to tailor their properties and gives rise to a striking feature of anchoring patterns that have no counterpart in normal colloidal crystals.

Identification of an Enterococcus faecium strain isolated from raw bovine milk co-harbouring the oxazolidinone resistance genes optrA and poxtA in China.

Oxazolidinones are potent antimicrobial agents used to treat human infections caused by multidrug-resistant Gram-positive bacteria. The growing resistance to oxazolidinones poses a significant threat to public health. In August 2021, a linezolid-resistant Enterococcus faecium BN83 was isolated from a raw milk sample of cow in Inner Mongolia, China. This isolate exhibited a multidrug resistance phenotype and was resistant to most of drugs tested including linezolid and tedizolid. PCR detection showed that two mobile oxazolidinones resistance genes, optrA and poxtA, were present in this isolate. Whole genome sequencing analysis revealed that the genes optrA and poxtA were located on two different plasmids, designated as pBN83-1 and pBN83-2, belonging to RepA_N and Inc18 families respectively. Genetic context analysis suggested that optrA gene on plasmid pBN83-1 was located in transposon Tn6261 initially found in E. faecalis. Comprehensive analysis revealed that Tn6261 act as an important horizontal transmission vector for the spread of optrA in E. faecium. Additionally, poxtA-bearing pBN83-2 displayed high similarity to numerous plasmids from Enterococcus of different origin and pBN83-2-like plasmid represented a key mobile genetic element involved in movement of poxtA in enterococcal species. The presence of optrA- and poxtA-carrying E. faecium in raw bovine milk represents a public health concern and active surveillance is urgently warranted to investigate the prevalence of oxazolidinone resistance genes in animal-derived food products.

A comprehensive evaluation of influencing factors of neonicotinoid insecticides (NEOs) in farmland soils across China: First focus on film mulching.

Neonicotinoid insecticide (NEO) residues in agricultural soils have concerning and adverse effects on agroecosystems. Previous studies on the effects of farmland type on NEOs are limited to comparing greenhouses with open fields. On the other hand, both NEOs and microplastics (MPs) are commonly found in agricultural fields, but their co-occurrence characteristics under realistic fields have not been reported. This study grouped farmlands into three types according to the covering degree of the film, collected 391 soil samples in mainland China, and found significant differences in NEO residues in the soils of the three different farmlands, with greenhouse having the highest NEO residue, followed by farmland with film mulching and farmland without film mulching (both open fields). Furthermore, this study found that MPs were significantly and positively correlated with NEOs. As far as we know this is the first report to disclose the association of film mulching and MPs with NEOs under realistic fields. Moreover, multiple linear regression and random forest models were used to comprehensively evaluate the factors influencing NEOs (including climatic, soil, and agricultural indicators). The results indicated that the random forest model was more reliable, with MPs, farmland type, and total nitrogen having higher relative contributions.

Spatial distribution, compositional characteristics, and source apportionment of legacy and novel per- and polyfluoroalkyl substances in farmland soil: A nationwide study in mainland China.

China, as one of the largest global producers and consumers of per- and poly-fluoroalkyl substances (PFASs), faces concerning levels of PFAS pollution in soil. However, knowledge of their occurrence in agricultural soils of China on the national scale remains unknown. Herein, the first nationwide survey was done by collecting 352 soil samples from 31 provinces in mainland China. The results indicated that the Σ24PFASs concentrations were 74.3 - 24880.0 pg/g, with mean concentrations of PFASs in decreasing order of legacy PFASs > emerging PFASs > PFAS precursors (640.2 pg/g, 340.7 pg/g, and 154.9 pg/g, respectively). The concentrations in coastal eastern China were distinctly higher than those in inland regions. Tianjin was the most severely PFASs-contaminated province because of rapid urban industrialization. This study further compared the PFAS content in monoculture and multiple cropping farmland soils, finding the concentrations of PFASs were high in soils planted with vegetable and fruit monocultures. Moreover, a positive matrix factorization (PMF) model was employed to identify different sources of PFASs. Fluoropolymer industries and aqueous film-forming foams were the primary contributors. The contributions from different emission sources varied across the seven geographical regions. This study provides new baseline data for prevention and control policies for reducing pollution.

Enhancing cryo-EM structure prediction with DeepTracer and AlphaFold2 integration.

Understanding the protein structures is invaluable in various biomedical applications, such as vaccine development. Protein structure model building from experimental electron density maps is a time-consuming and labor-intensive task. To address the challenge, machine learning approaches have been proposed to automate this process. Currently, the majority of the experimental maps in the database lack atomic resolution features, making it challenging for machine learning-based methods to precisely determine protein structures from cryogenic electron microscopy density maps. On the other hand, protein structure prediction methods, such as AlphaFold2, leverage evolutionary information from protein sequences and have recently achieved groundbreaking accuracy. However, these methods often require manual refinement, which is labor intensive and time consuming. In this study, we present DeepTracer-Refine, an automated method that refines AlphaFold predicted structures by aligning them to DeepTracers modeled structure. Our method was evaluated on 39 multi-domain proteins and we improved the average residue coverage from 78.2 to 90.0% and average local Distance Difference Test score from 0.67 to 0.71. We also compared DeepTracer-Refine with Phenixs AlphaFold refinement and demonstrated that our method not only performs better when the initial AlphaFold model is less precise but also surpasses Phenix in run-time performance.

Fostering employees' innovative behavior: The importance of proactive personality and work-related flow.

Employees' innovative behaviors (EIB) play a crucial role in driving enterprises' innovation and enabling them to adapt to the complex business environment. The purpose of this study is to examine the role of proactive personality in EIB, whereby a mediating effect of work-related flow is proposed in this relationship. The moderating effect of organizational innovation climate is also examined on the indirect of proactive personality on EIB through work-related flow. With purposive sampling, a questionnaire survey was conducted on front-line employees of two digital cultural and creative industrial parks in Southwest China. A total of 279 valid questionnaires were used for hypothesis verification. The findings indicate that employees' proactive personality has a significant positive effect on EIB. Employees with a proactive personality are more likely to experience work-related flow, which in turn promotes their EIB. However, we did not find evidence of the organizational innovation climate moderating the relationship between proactive personality and EIB.

Nomogram to Predict 90-Day All-Cause Mortality in Acute Ischemic Stroke Patients after Endovascular Thrombectomy.

OBJECTIVE: Although Endovascular Thrombectomy (EVT) significantly improves the prognosis of Acute Ischemic Stroke (AIS) patients with large vessel occlusion, the mortality rate remains higher. This study aimed to construct and validate a nomogram for predicting 90-day all-cause mortality in AIS patients with large vessel occlusion and who have undergone EVT. METHODS: AIS patients with large vessel occlusion in the anterior circulation who underwent EVT from May 2017 to December 2022 were included. 430 patients were randomly split into a training group (N=302) and a test group (N=128) for the construction and validation of our nomogram. In the training group, multivariate logistic regression analysis was performed to determine the predictors of 90-day all-cause mortality. The C-index, calibration plots, and decision curve analysis were applied to evaluate the nomogram performance. RESULTS: Multivariate logistic regression analysis revealed neurological deterioration during hospitalization, age, baseline National Institutes of Health Stroke Scale (NIHSS) score, occlusive vessel location, malignant brain edema, and Neutrophil-to-lymphocyte Ratio (NLR) as the independent predictors of 90-day all-cause mortality (all p ≤ 0.039). The C-index of the training and test groups was 0.891 (95%CI 0.848-0.934) and 0.916 (95% CI: 0.865-0.937), respectively, showing the nomogram to be well distinguished. The Hosmer-Lemeshow goodness-of-fit test revealed the p-values for both the internal and external verification datasets to be greater than 0.5. CONCLUSION: Our nomogram has incorporated relevant clinical and imaging features, including neurological deterioration, age, baseline NIHSS score, occlusive vessel location, malignant brain edema, and NLR ratio, to provide an accurate and reliable prediction of 90-day all-cause mortality in AIS patients undergoing EVT.

Uncovering the Effect of A-Site Cations on Localized Excitons Photoluminescence of Manganese-Doped Zinc Chloride Nanocrystals.

Elucidating the key factors that affect the localized excitons (LEs) photoluminescence (PL) in lead-free metal halide nanocrystals (NCs) is important for their optoelectronic applications. However, the effect of A-site cations on LEs based PL is not well understood. Herein, we varied the A-site cation ratio (Rb/Cs) to investigate the influence on LEs based PL in manganese-doped zinc chloride NCs. Through time-resolved photoluminescence (TR-PL) spectra and density functional theory (DFT) calculations, we discovered that Cl vacancy is energetically more favorable in Mn2+-doped Rb3ZnCl5 NCs compared to Mn2+-doped Cs3ZnCl5 NCs. The higher concentration of Cl vacancy increases the nonradiative recombination process in Rb3ZnCl5:Mn2+ NCs, ultimately determining the PL efficiency. This research enhances the understanding of the A-site cation effect on LEs-based PL in lead-free metal halide NCs.

A pharmacokinetic study comparing the biosimilar HEC14028 and Dulaglutide (Trulicity®) in healthy Chinese subjects.

This study aimed to evaluate the pharmacokinetics (PKs), safety, and immunogenicity of the biosimilar HEC14028 compared to reference Trulicity® (dulaglutide) in healthy male Chinese subjects. This study was a single-center, randomized, open, single-dose, parallel-controlled comparative Phase I clinical trial, including a screening period of up to 14 days, a 17-day observation period after administration, and a 7-day safety follow-up period. A total of 68 healthy male subjects were randomly assigned (1:1) to the test group (HEC14028) and the reference group (dulaglutide) (single 0.75 mg abdominal subcutaneous dose). The primary objective was to evaluate the pharmacokinetic characteristics of HEC14028 and compare the pharmacokinetic similarities between HEC14028 and dulaglutide. The primary PK endpoints were maximum plasma concentration (Cmax) and area under the blood concentration-time curve from zero time to the estimated infinite time (AUC0-∞). The study results showed that HEC14028 and dulaglutide were pharmacokinetically equivalent: 90% confidence interval (CI) of Cmax and AUC0-∞ geometric mean ratios were 102.9%-122.0% and 97.1%-116.9%, respectively, which were both within the range of 80.00%-125.00%. No grade 3 or above treatment emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to withdrawal from the trial, or TEAEs leading to death were reported in this study. Both HEC14028 and dulaglutide showed good and similar safety profiles, and no incremental immunogenicity was observed in subjects receiving HEC14028 and dulaglutide.

Nematode Uptake Preference toward Different Nanoplastics through Avoidance Behavior Regulation.

Expounding bioaccumulation pathways of nanoplastics in organisms is a prerequisite for assessing their ecological risks in the context of global plastic pollution. Invertebrate uptake preference toward nanoplastics is a key initial step of nanoplastic food chain transport that controls their global biosafety, while the biological regulatory mechanism remains unclear. Here, we reveal a preferential uptake mechanism involving active avoidance of nanoplastics by Caenorhabditis elegans and demonstrate the relationship between the uptake preference and nanoplastic characteristics. Nanoplastics with 100 nm in size or positive surface charges induce stronger avoidance due to higher toxicity, causing lower accumulation in nematodes, compared to the 500 nm-sized or negatively charged nanoplastics, respectively. Further evidence showed that nematodes did not actively ingest any types of nanoplastics, while different nanoplastics induced defense responses in a toxicity-dependent manner and distinctly stimulated the avoidance behavior of nematodes (ranged from 15.8 to 68.7%). Transcriptomics and validations using mutants confirmed that the insulin/IGF signaling (IIS) pathway is essential for the selective avoidance of nanoplastics. Specifically, the activation of DAF-16 promoted the IIS pathway-mediated defense against nanoplastics and stimulated the avoidance behavior, increasing the survival chances of nematodes. Considering the genetical universality of this defense response among invertebrates, such an uptake preference toward certain nanoplastics could lead to cascaded risks in the ecosystem.

Development of synthetic small regulatory RNA for Rhodococcus erythropolis.

Rhodococci have been regarded as ideal chassis for biotransformation, biodegradation, and biosynthesis for their unique environmental persistence and robustness. However, most species of Rhodococcus are still difficult to metabolically engineer due to the lack of genetic tools and techniques. In this study, synthetic sRNA strategy was exploited for gene repression in R. erythropolis XP. The synthetic sRNA based on the RhlS scaffold from Pseudomonas aeruginosa functions better in repressing sfgfp expression than those based on E. coli MicC, SgrS, and P. aeruginosa PrrF1-2 scaffold. The RhlS-based sRNAs were applied to study the influence of sulfur metabolism on biodesulfurization (BDS) efficiency in R. erythropolis XP and successfully identified two genes involved in sulfur metabolism that affect the BDS efficiency significantly. The RhlS-based synthetic sRNAs show promise in the metabolic engineering of Rhodococcus and promote the industrial applications of Rhodococcus in environmental remediation and biosynthesis.

Probing the geometric and electronic structures of the transition metal oxides RhOn-1/0 (n = 1-4) clusters.

The photoelectron spectroscopies of RhOn- (n = 1-2) were obtained via using the photoelectron velocity-map imaging (PE-VMI) approach. The experimental values of the adiabatic detachment energy (ADE) and vertical detachment energy (VDE) for RhO- were reported to be 1.58 ± 0.02 eV. The experimental AED and VDE values of RhO2- were reported to be 2.70 ± 0.02 eV and 2.79 ± 0.02 eV, respectively. The vibrational frequencies of RhO- and RhO2- measured from photoelectron spectra (PES) were 817(76) cm-1 and 932(55) cm-1, respectively. Based on the density functional theory (DFT), the RhOn-1/0 (n = 1-4) clusters were investigated. The optimized configurations of corresponding ground states and low-lying clusters were discovered. Meanwhile, the simulated photoelectron spectroscopy (PES) of RhOn- (n = 1-4) and the theoretical ADE and VDE values of RhOn- (n = 1-4) clusters were unveiled to assist future experimental studies of Rhodium oxide clusters. Moreover, the associated molecular orbitals (MOs), natural population analysis (NPA) and bond order analysis have been utilized to investigate the chemical bonding in these groups.

Electron Donor-Acceptor Complex Driven Photocatalyst-Free Trifluoromethylation of Heterocycles.

Heterocyclic trifluoromethylation is efficiently initiated through a photochemical reaction utilizing an electron donor-acceptor (EDA) complex, proceeding smoothly without the use of photocatalysts, transition-metal catalysts, or additional oxidants. This method has been optimized through extensive experimentation, demonstrating its versatility and efficacy across various substrates, including quinoxalinones, coumarins, and indolones. Notably, this approach enables the practical synthesis of trifluoromethylated quinoxalinones on a gram scale. Mechanistic investigations that incorporate radical trapping and ultraviolet/visible spectroscopy, confirmed the formation of the an EDA complex and elucidated the reaction pathways. This study highlights the crucial role of EDA photoactivation in trifluoromethylation, significantly expanding the application scope of EDA complexes in chemical synthesis.

Predicting pathological complete response to neoadjuvant chemotherapy in breast cancer patients: use of MRI radiomics data from three regions with multiple machine learning algorithms.

OBJECTIVE: To construct a multi-region MRI radiomics model for predicting pathological complete response (pCR) in breast cancer (BCa) patients who received neoadjuvant chemotherapy (NACT) and provide a theoretical basis for the peritumoral microenvironment affecting the efficacy of NACT. METHODS: A total of 133 BCa patients who received NACT, including 49 with confirmed pCR, were retrospectively analyzed. The radiomics features of the intratumoral region, peritumoral region, and background parenchymal enhancement (BPE) were extracted, and the most relevant features were obtained after dimensional reduction. Then, combining different areas, multivariate logistic regression analysis was used to select the optimal feature set, and six different machine learning models were used to predict pCR. The optimal model was selected, and its performance was evaluated using receiver operating characteristic (ROC) analysis. SHAP analysis was used to examine the relationship between the features of the model and pCR. RESULTS: For signatures constructed using three individual regions, BPE provided the best predictions of pCR, and the diagnostic performance of the intratumoral and peritumoral regions improved after adding the BPE signature. The radiomics signature from the combination of all the three regions with the XGBoost machine learning algorithm provided the best predictions of pCR based on AUC (training set: 0.891, validation set: 0.861), sensitivity (training set: 0.882, validation set: 0.800), and specificity (training set: 0.847, validation set: 0.84). SHAP analysis demonstrated that LZ_log.sigma.2.0.mm.3D_glcm_ClusterShade_T12 made the greatest contribution to the predictions of this model. CONCLUSION: The addition of the BPE MRI signature improved the prediction of pCR in BCa patients who received NACT. These results suggest that the features of the peritumoral microenvironment are related to the efficacy of NACT.

Discovery of Novel PD-L1 Small-Molecular Inhibitors with Potent In Vivo Anti-tumor Immune Activity.

Programmed death-ligand 1 (PD-L1) has surfaced as a promising therapeutic target for various cancers due to its pivotal role in facilitating tumor immune evasion. Herein, we report a series of novel small-molecule PD-L1 inhibitors exhibiting remarkable inhibitory activity against the PD-1/PD-L1 interaction (X18: IC50 = 1.3 nM) and reinstating the suppressive effect of PD-L1 on T cells (X18: EC50 = 152.8 nM). Crystallographic studies revealed the binding mode of X18 and PD-L1. Through a rational prodrug design approach, we have successfully optimized the oral pharmacokinetic properties of X22, effectively addressing the poor oral pharmacokinetic profile of PD-L1 small-molecule inhibitors. Notably, X22 demonstrated significant antitumor efficacy in murine models of MC38 and CT26 colon cancer through the upregulation of tumor infiltration and cytotoxicity of CD8+ T cells partially. These findings offer promising prospects for the advancement of PD-L1 inhibitors as innovative agents in cancer immunotherapy.

Contamination and Control of Mycotoxins in Grain and Oil Crops.

Mycotoxins are carcinogenic, teratogenic and mutagenic toxic compounds produced by some filamentous fungi, which are extremely harmful to corn, rice, wheat, peanut, soybean, rapeseed and other grain and oil crops, and seriously threaten environmental safety, food safety and human health. With the rapid increase in the global population and the expansion of the main crop planting area, mycotoxin contamination has increased year by year in agricultural products. The current review aimed to summarize the contamination status and harmful effects of major mycotoxins of grain and oil crops and the environmental factors that impact mycotoxin contamination. Further, control measures of mycotoxin contamination, especially the biological control strategies, were discussed.

Dual vector millimeter-wave signal generation based on optical carrier suppression modulation and direct detection with one photodetector.

We propose a novel, to the best of our knowledge, scheme for dual vector millimeter-wave (mm-wave) signal generation and transmission, based on optical carrier suppression (OCS) modulation, precoding, and direct detection by a single-ended photodiode (PD). At the transmitter side, two independent vector radio frequency (RF) signals with precoding, generated via digital signal processing (DSP), are used to drive an in-phase/quadrature (I/Q) modulator operating at the optical OCS modulation mode to simultaneously generate two independent frequency-doubling optical vector mm-wave signals, which can reduce the bandwidth requirement of transmitter's components and enhance spectral efficiency. With the aid of the single-ended PD and subsequent DSP at the receiver side, two independent frequency-doubling vector mm-wave signals can be separated and demodulated without data error. Based on our proposed scheme, we experimentally demonstrate the generation, transmission, and detection of 2-Gbaud 30-GHz quadrature-phase-shift-keying (QPSK) and 2-Gbaud 46-GHz QPSK signals over 10-km single-mode fiber-28 (SMF-28) and 1-m wireless transmission. The results indicate that the bit-error ratio (BER) of the dual vector mm-wave signals can each reach the hard-decision forward-error-correction (HD-FEC) threshold of 3.8 × 10-3.

Discovery of a botanical compound as a broad-spectrum inhibitor against gut microbial ß-glucuronidases from the Tibetan medicine Rhodiola crenulata.

Gut microbial ß-glucuronidases (gmß-GUS) played crucial roles in regulating a variety of endogenous substances and xenobiotics on the circulating level, thus had been recognized as key modulators of drug toxicity and human diseases. Inhibition or inactivation of gmß-GUS enzymes has become a promising therapeutic strategy to alleviate drug-induced intestinal toxicity. Herein, the Rhodiola crenulata extract (RCE) was found with potent and broad-spectrum inhibition on multiple gmß-GUS enzymes. Subsequently, the anti-gmß-GUS activities of the major constituents in RCE were tested and the results showed that 1,2,3,4,6-penta-O-galloyl-ß-d-glucopyranose (PGG) acted as a strong and broad-spectrum inhibitor on multiple gmß-GUS (including EcGUS, CpGUS, SaGUS, and EeGUS). Inhibition kinetic assays demonstrated that PGG effectively inhibited four gmß-GUS in a non-competitive manner, with the Ki values ranging from 0.12 µM to 1.29 µM. Docking simulations showed that PGG could tightly bound to the non-catalytic sites of various gmß-GUS, mainly via hydrogen bonding and aromatic interactions. It was also found that PGG could strongly inhibit the total gmß-GUS activity in mice feces, with the IC50 value of 1.24 µM. Collectively, our findings revealed that RCE and its constituent PGG could strongly inhibit multiple gmß-GUS enzymes, suggesting that RCE and PGG could be used for alleviating gmß-GUS associated enterotoxicity.

Epidermal microorganisms contributed to the toxic mechanism of nZVI and TCEP in earthworms by robbing metal elements and nutrients.

Disrupting effects of pollutants on symbiotic microbiota have been regarded as an important mechanism of host toxicity, with most current research focusing on the intestinal microbiota. In fact, the epidermal microbiota, which participates in the nutrient exchange between hosts and environments, could play a crucial role in host toxicity via community changes. To compare the contributions of intestinal and epidermal symbiotic microorganisms to host toxicity, this study designed single and combined scenarios of soil contamination [nano zero-valent iron (nZVI) and tris (2-chloroethyl) phosphate (TCEP)], and revealed the coupling mechanisms between intestinal/epidermal symbiotic bacterial communities and earthworm toxicological endpoints. Microbiome analysis showed that 15% of intestinal microbes were highly correlated with host endpoints, compared to 45% of epidermal microbes showing a similar correlation. Functional comparisons revealed that key species on the epidermis were mainly heterotrophic microbes with genetic abilities to utilize metal elements and carbohydrate nutrients. Further verifications demonstrated that when facing the co-contamination of nZVI and TCEP, certain symbiotic microorganisms became dominant and consumed zinc, copper, and manganese along with saccharides and amino acids, which may be responsible for the nutritional deficiencies in the host earthworms. The findings can enrich the understanding of the coupling relationship between symbiotic microorganisms and host toxicity, highlighting the importance of epidermal microorganisms in host resistance to environmental pollution.