The Characteristics of Coronary Artery Lesions in COVID-19 Infected Patients with Coronary Artery Disease:An Optical Coherence Tomography Study.

Coronavirus disease 2019 (COVID-19) may predispose patients to cardiac injuries but whether COVID-19 infection affects the morphological features of coronary plaques to potentially influence the outcome of patients with coronary artery disease (CAD) remains unknown. By using optical coherence tomography (OCT), this study compared the characteristics of coronary plaque in CAD patients with/without COVID-19 infection. The 206 patients were divided into two groups. The COVID-19 group had 113 patients between December 7, 2022 and March 31, 2023 who received optical coherence tomography (OCT) assessment after China decided to lift the restrict on COVID-19 and had a history of COVID-19 infection. The non-COVID-19 group had 93 patients without COVID-19 infection who underwent OCT before December 7, 2022. The COVID-19 group demonstrated a higher incidence of plaque ruptures (53.1% vs. 38.7%, p=0.039), erosions (28.3% vs. 11.8%, p=0.004), fibrous (96.5% vs. 89.2%, p=0.041) and diffuse lesions (73.5% vs. 50.5%, p<0.001) compared to the non-COVID-19 group, whereas non-COVID-19 group exhibited a higher frequency of cholesterol crystals (83.9% vs. 70.8%, p=0.027), deep calcifications (65.6% vs. 51.3%, p=0.039) and solitary lesions (57.0% vs. 34.5%, p=0.001). Kaplan-Meier survival analysis revealed a significantly lower major adverse cardiac events (MACE)-free probability in COVID-19 group (91.6% vs. 95.5%, P=0.006) than non-COVID-19 group. In conclusion, OCT demonstrated that COVID-19 infection is associated with coronary pathological changes such as more plaque ruptures, erosions, and fibrosis as well as diffuse lesions. Further, COVID-19 infection is associated with the higher propensity for acute coronary events and the higher risk of MACE in CAD patients.

Efficacy and safety of regorafenib in the treatment of metastatic colorectal cancer: a retrospective cohort study.

Background: The majority of studies of regorafenib now were small-sample and single-arm, which potentially limits the strength of evidence. We conduct the study to identify the efficacy and safety of regorafenib for patients with metastatic colorectal cancer (mCRC) in real-world applications. Methods: mCRC patients who underwent regorafenib second line or post-second line treatment with at least one assessable lesion were analyzed. Patients received different doses of regorafenib and different combination regimens. The patients were followed up with laboratory tests and imaging examinations every 3 months to evaluate the efficacy and adverse events (AEs). The primary endpoint of this study was median overall survival (mOS), and the secondary endpoints were median progression-free survival (mPFS), the objective response rate (ORR), the disease control rate (DCR), and AEs. Results: A total of 77 patients (45 males and 32 females, aged 58.80±11.65 years) were enrolled in the study. Most primary tumors were located in the rectum (59.74%), and the vast majority of tumors (89.62%) had an adenocarcinoma histological type. The 77 patients had an mOS of 17.8 months, a progression-free survival (PFS) of 4.63 months, an ORR of 6.76%, and a DCR of 55.41%. Patients underwent regorafenib third-line therapy had significantly higher overall survival (OS) than those underwent regorafenib post- third-line treatment (P=0.03). The neutrophil to lymphocyte ratio (NLR) was an independent factor affecting the OS of the mCRC patients [hazard ratio (HR) =1.12, P=0.03]. In both univariate and multivariate analyses, discontinued use of regorafenib after progression reduced patients' PFS (HR =3.07, P<0.001; HR =2.78, P=0.007). In terms of the tolerated dose, patients receiving 120 mg regorafenib had the longest OS numbers, but there was no statistical difference. We analyzed the effect of the baseline NLR on the OS of patients receiving regorafenib combined with immunotherapy, and found that the NLR ratio cut-off value was 4.4, and patients with a NLR ratio ≤4.4 benefited significantly in terms of OS (P=0.03). The AEs included 21 (27.27%) cases of hand and foot skin reaction, 15 (19.48%) cases of fatigue, 9 (11.69%) cases of pain, 9 (11.69%) cases of nausea, 9 (11.69%) cases of fever, 9 (11.69%) cases of cough, and so on. Conclusions: Regorafenib is relatively effective and safe as a third-line and posterior treatment of mCRC. Patients underwent regorafenib third-line therapy had longer OS than those underwent regorafenib post- third-line treatment. Moreover, PFS benefits can still be obtained by continuing regorafenib treatment after progression. Grade 1-2 AEs were common, but these were usually tolerated by most patients.

Room-temperature ferromagnetism, half-metallicity and spin transport in monolayer CrSc2Te4-based magnetic tunnel junction devices.

The discovery of novel two-dimensional (2D) half-metallic materials with a robust ferromagnetic (FM) order and a high Curie temperature (Tc) is attractive for the advancement of next-generation spintronic devices. Here, we propose a monolayer with stable 2D intrinsic FM half-metallicity, i.e., the CrSc2Te4 monolayer, which was constructed by intercalating a monolayer of 1T-CrTe2-type sandwiched between two layers of 2H-ScTe2 monolayers. Our calculations reveal that it exhibits exceptional dynamical, thermal, and mechanical stabilities accompanied by a robust half-metallicity characterized by a wide bandgap of 1.02 eV and FM ordering with a high Tc of 326 K. Notably, these properties remain intact in almost the entire range of the biaxial strain from -5% to 5%. Furthermore, our investigations demonstrate excellent spin transport capabilities, including an outstanding spin-filtering effect, and a remarkably high tunneling magnetoresistance ratio peaking at 6087.07%. The remarkable magnetic features of the 2D CrSc2Te4 monolayer with room temperature FM, intrinsic half-metallicity, and 100% spin-polarization make it a promising candidate for the next-generation high-performance spintronic nanodevices as well as high-density magnetic recording and sensors.

The prognostic role of lymphocyte-to-monocyte ratio in patients with resectable pancreatic cancer: a systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis examined whether the lymphocyte-to-monocyte ratio (LMR) can serve as an indicator for predicting the prognosis of patients with resectable pancreatic cancer. Patients and Methods: This meta-analysis was registered with PROSPERO: CRD42023461260. A systematic literature search was conducted in the PubMed, Embase, Cochrane, and Web of Science databases up to September 2023 to assess whether LMR can predict the prognosis of patients with resectable pancreatic cancer. The outcomes measured included subgroup analyses of overall survival (OS) with hazard ratios (HR) and confidence intervals of geographical region, patient population, and LMR threshold. A sensitivity analysis was also performed for OS and HR and confidence intervals were calculated for recurrence-free survival (RFS). Results: A total of 14 eligible articles, comprising 4,019 patients, were included in the comprehensive analysis. The results of this comprehensive analysis indicate that LMR is a robust predictor of OS, demonstrating strong prognostic significance (HR = 0.55, 95% CI [0.44-0.69], I2 = 79%, P < 0.00001). This predictive significance extended to various types of pancreatic cancer, such as pancreatic ductal adenocarcinoma (HR = 0.73, 95% CI [0.57-0.93], I2 = 46%, P = 0.01), pancreatic neuroendocrine neoplasms (HR = 0.81, 95% CI [0.66-0.99], P = 0.04) and other subtypes (HR = 0.40, 95% CI [0.22-0.72], I2 = 89%, P < 0.00001), but not to pancreatic head cancer (HR = 0.46, 95% CI [0.16-1.13], I2 = 59%, P = 0.12). LMR retained its predictive value across different regions, including Asia (HR = 0.62, 95% CI [0.47-0.76], I2 = 68%, P < 0.0001), Europe (HR = 0.78, 95% CI [0.67-0.91], I2 = 0%, P = 0.002), and the Americas (HR = 0.14, 95% CI [0.08-0.24], I2 = 0%, P < 0.00001). Notably, both LMR cut-off values greater than or equal to three (HR = 0.62, 95% CI [0.47-0.82], I2 = 67%, P = 0.0009) and less than three (HR = 0.47, 95% CI [0.32-0.69], I2 = 85%, P = 0.0001) exhibited prognostic significance. The sensitivity analysis for OS confirmed the strong predictive value of LMR, whereas LMR did not exhibit predictive significance for RFS (HR = 0.35, 95% CI [0.09-1.32], I2 = 95%, P = 0.12). In both subgroups categorized by Newcastle-Ottawa Scale (NOS) scores of ≥7 (HR = 0.66, 95% CI [0.54-0.80], I2 = 53%, P = 0.04) and <7 (HR = 0.41, CI [0.23-0.72], I2 = 89%, P < 0.00001), LMR was demonstrated to have predictive value. Conclusion: Despite the observed heterogeneity and potential biases in the included studies, the findings of this study suggest that LMR may serve as a valuable predictor of OS in patients with resectable pancreatic cancer.

Gut microbiome and metabolome alterations in traditional Chinese medicine damp-heat constitution following treatment with a Chinese patent medicine and lifestyle intervention.

BACKGROUND: The gut microbiota is crucial in human health and diseases. Traditional Chinese Medicine Constitution (TCMC) divides people into those with a balanced constitution (Ping-he [PH]) and those with an unbalanced constitution. Dampness-heat constitution (Shi-re [SR]) is a common unbalanced constitution in the Chinese population and is susceptible to diseases. However, unbalanced constitutions can be regulated by Chinese medicine and lifestyle interventions in clinical practice. Ermiao Pill (EMP) is a Chinese medicine known for clearing heat and draining dampness and improving SR. However, the efficacy and mechanism of EMP are unclear. HYPOTHESIS/PURPOSE: To determine alterations in the gut microbiota and metabolome in SR and any changes after EMP treatment combined with lifestyle intervention. STUDY DESIGN: Randomized clinical trial. METHODS: We enrolled 112 healthy SR individuals and evaluated the efficacy of EMP along with lifestyle interventions. We further assessed serum cytokine levels, serum and urinary metabolomes, and the gut microbiota by 16S rRNA gene sequencing analysis before and after the EMP and lifestyle interventions. RESULTS: 107 SR individuals (55 in the intervention group and 52 in the control group) completed the 1-month-intervention and 1-year-follow-up. The intervention group significantly improved their health status within 1 month, with a reduced SR symptom score, and the efficacy lasted to the 1-year follow-up. The control group needed a further 6 months to reduce the SR symptom score. The gut microbiota of PH individuals was more diverse and had significantly higher proportions of many bacterial species than the SR. Microbiota co-occurrence network analysis showed that SR enriches metabolites correlating with microbial community structure, consistent with traits of healthy SR-enriched microbiota. CONCLUSION: EMP combined with lifestyle intervention produced health benefits in SR individuals. Our study indicates a pivotal role of gut microbiota and metabolome alterations in distinguishing between healthy SR and PH. Furthermore, the study reveals structural changes of gut microbiota and metabolites induced by EMP and lifestyle intervention. The treatment enriched the number of beneficial bacteria, such as Akkermansia muciniphila and Lactobacillus in the gut. Our findings provide a strong indication that several metabolite factors are associated with the gut microbiota. Moreover, the gut microbiome and metabolome might be powerful tools for TCMC diagnosis and personalized therapy.

Novel mechanisms of Anshen Dingzhi prescription against PTSD: Inhibiting DCC to modulate synaptic function and inflammatory responses.

ETHNOPHARMACOLOGICAL RELEVANCE: Anshen Dingzhi prescription (ADP), documented in "Yi Xue Xin Wu", is a famous prescription for treating panic-related mental disorders such as post-traumatic stress disorder (PTSD). However, the underlying mechanism remains unclear. AIM OF THE STUDY: This study aimed to investigate the mechanisms by which ADP intervened in PTSD-like behaviors. METHODS: A mouse model of single prolonged stress (SPS) was established to evaluate the ameliorative effects and mechanisms of ADP on PTSD. Behavioral tests were used to assess PTSD-like behaviors in mice; transmission electron microscopy was used to observe changes in the ultrastructure of hippocampal synapses, and western blot, immunofluorescence, and ELISA were used to detect the expression of hippocampal deleted in colorectal cancer (DCC) and downstream Ras-related C3 botulinum toxin substrate 1 (Rac1) - P21-activated kinase 1 (PAK1) signal, as well as levels of synaptic proteins and inflammatory factors. Molecular docking technology simulated the binding of potential brain-penetrating components of ADP to DCC. RESULTS: SPS induced PTSD-like behaviors in mice and increased expression of hippocampal netrin-1 (NT-1) and DCC on the 14th day post-modeling, with concurrent elevation in serum NT-1 levels. Simultaneously, SPS also decreased p-Rac1 level and increased p-PAK1 level, the down-stream molecules of DCC. Lentiviral overexpression of DCC induced or exacerbated PTSD-like behaviors in control and SPS mice, respectively, whereas neutralization antibody against NT-1 reduced DCC activation and ameliorated PTSD-like behaviors in SPS mice. Interestingly, downstream Rac1-PAK1 signal was altered according to DCC expression. Moreover, DCC overexpression down-regulated N-methyl-d-aspartate (NMDA) receptor 2A (GluN2A) and postsynaptic density 95 (PSD95), up-regulated NMDA receptor 2B (GluN2B) and increased neuroinflammatory responses. Administration of ADP (36.8 mg/kg) improved PTSD-like behaviors in the SPS mice, suppressed hippocampal DCC, and downstream Rac1-PAK1 signal, upregulated GluN2A and PSD95, downregulated GluN2B, and reduced levels of inflammatory factors NOD-like receptor protein 3 (NLRP3), nuclear factor kappa-B (NF-κB) and interleukin-6 (IL-6). Importantly, DCC overexpression could also reduce the ameliorative effect of ADP on PTSD. Additionally, DCC demonstrated a favorable molecular docking pattern with the potential brain-penetrating components of ADP, further suggesting DCC as a potential target of ADP. CONCLUSION: Our data indicate that DCC is a key target for the regulation of synaptic function and inflammatory response in the onset of PTSD, and ADP likely reduces DCC to prevent PTSD via modulating downstream Rac1-PAK1 pathway. This study provides a novel mechanism for the onset of PTSD and warrants the clinical application of ADP.

Zoonotic infections by avian influenza virus: changing global epidemiology, investigation, and control.

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

Discovery and Engineering of a Bacterial (+)-Pulegone Reductase for Efficient (-)-Menthol Biosynthesis.

The biosynthesis of valuable plant-derived monoterpene (-)-menthol from readily available feedstocks (e.g., (-)-limonene) is of great significance because of the high market demand for this product. However, biotransforming (+)-pulegone into (-)-menthone, the (-)-menthol precursor, through (+)-pulegone reductase (PGR) catalysis is inefficient because of the poor protein expression or catalytic efficiency (kcat/Km) of plant origin PGRs. In this study, a novel bacterial PGR from Pseudomonas resinovorans (PrPGR) was identified, and the most successful variant, PrPGRM2-1 (A50V/G53W), was obtained, showing respective 20-fold and 204-fold improvements in specific activity and catalytic efficiency. PrPGRM2-1 was employed to bioreduce (+)-pulegone, resulting in 4.4-fold and 35-fold enhancements in (-)-menthone titers compared with the bioreductions catalyzed by wild-type (WT) PrPGR and MpPGR, respectively. Furthermore, a whole-cell biocatalyst containing PrPGRM2-1, MpMMR, and BstFDH was constructed and achieved the highest (-)-menthol titer reported to date without externally supplemented NADPH/NADP+. Overall, this study details an efficient PGR with high catalytic efficiency that possesses great potential for (-)-menthol biosynthesis.

PTEN and P-4E-BP1 might be associated with postoperative recurrence of rectal cancer patients undergoing concurrent radiochemotherapy.

BACKGROUND: Local recurrence after surgery and radiochemotherapy seriously affects the prognosis of locally advanced rectal cancer (LARC) patients. Studies on molecular markers related to the radiochemotherapy sensitivity of cancers have been widely carried out, which might provide valued information for clinicians to carry out individual treatment. AIM: To find potential biomarkers of tumors for predicting postoperative recurrence. METHODS: In this study, LARC patients undergoing surgery and concurrent radiochemotherapy were enrolled. We focused on clinicopathological factors and PTEN, SIRT1, p-4E-BP1, and pS6 protein expression assessed by immunohistochemistry in 73 rectal cancer patients with local recurrence and 76 patients without local recurrence. RESULTS: The expression of PTEN was higher, while the expression of p-4E-BP1 was lower in patients without local recurrence than in patients with local recurrence. Moreover, TNM stage, lymphatic vessel invasion (LVI), PTEN and p-4E-BP1 might be independent risk factors for local recurrence after LARC surgery combined with concurrent radiochemotherapy. CONCLUSIONS: This study suggests that PTEN and p-4E-BP1 might be potential biomarkers for prognostic prediction and therapeutic targets for LARC.

Pharmacokinetic/Pharmacodynamic Assessment of the Structural Refinement of Clopidogrel Focusing on the Balance between Bioactivation and Deactivation.

The delicate balance between ischemic and bleeding risks is a critical factor in antiplatelet therapy administration. Clopidogrel and prasugrel, belonging to the thienopyridine class of antiplatelet drugs, are known for their variability in individual responsiveness and high incidence of bleeding events, respectively. The present study is centered on the development and assessment of a range of deuterated thienopyridine derivatives, leveraging insights from structure-pharmacokinetic relationships of clopidogrel and prasugrel. Our approaches were grounded in the molecular framework of clopidogrel and incorporated the C2-pharmacophore design from prasugrel. The selection of ester or carbamate substituents at the C2-position facilitated the generation of the 2-oxointermediate through hydrolysis, akin to prasugrel, thereby bypassing the issue of CYP2C19 dependency. The bulky C2-pharmacophore in our approach distinguishes itself from prasugrel's acetyloxy substituent by exhibiting a moderated hydrolysis rate, resulting in a more gradual formation of the active metabolite. Excessive and rapid release of the active metabolite, believed to be linked with an elevated risk of bleeding, is thus mitigated. Our proposed structural modification retains the hydrolysis-sensitive methyl ester of clopidogrel but substitutes it with a deuterated methyl group, shown to effectively reduce metabolic deactivation. Three promising compounds demonstrated a pharmacokinetic profile similar to that of clopidogrel at four times the dose, while also augmenting its antiplatelet activity. SIGNIFICANCE STATEMENT: Inspired by the structure-pharmacokinetic relationship of clopidogrel and prasugrel, a range of clopidogrel derivatives were designed, synthesized, and assessed. Among them, three promising compounds have been identified, striking a delicate balance between efficacy and safety for antiplatelet therapy. Additionally, the ozagrel prodrug conjugate was discovered to exert a synergistic therapeutic effect alongside clopidogrel.

Turning Ultra-Low Coercivity and Ultra-High Temperature Stability Within 897 K via Continuous Crystal Ordering Fluctuations.

High-performance soft magnetic materials are important for energy conservation and emission reduction. One challenge is achieving a combination of reliable temperature stability, high resistivity, high Curie temperature, and high saturation magnetization in a single material, which often comes at the expense of intrinsic coercivity-a typical trade-off in the family of soft magnetic materials with homogeneous microstructures. Herein, a nanostructured FeCoNiSiAl complex concentrated alloy is developed through a hierarchical structure strategy. This alloy exhibits superior soft magnetic properties up to 897 K, maintaining an ultra-low intrinsic coercivity (13.6 A m-1 at 297 K) over a wide temperature range, a high resistivity (138.08 µΩ cm-1 at 297 K) and the saturation magnetization with only a 16.7% attenuation at 897 K. These unusual property combinations are attributed to the dual-magnetic-state nature with exchange softening due to continuous crystal ordering fluctuations at the atomic scale. By deliberately controlling the microstructure, the comprehensive performance of the alloy can be tuned and controlled. The research provides valuable guidance for the development of soft magnetic materials for high-temperature applications and expands the potential applications of related functional materials in the field of sustainable energy.

Atomic-Level Catalyst Coupled with Metal Oxide Heterostructure for Promoting Kinetics of Lithium-Sulfur Batteries.

Despite the low competitive cost and high theoretical capacity of lithium-sulfur (Li-S) batteries, their practical application is severely hindered by the lithium polysulfide (LiPS) shuttling and low conversion efficiency. Herein, the electronic structure of hollow Titanium dioxide nanospheres is tunned by single Iron atom dopants that can cooperatively enhance LiPS absorption and facilitate desired redox reaction in practical Li-S batteries, further suppressing the notorious shuttle effect, which is consistent with theoretical calculations and in situ UV/vis investigation. The obtained electrode with massive active sites and lower energy barrier for sulfur conversions exhibits exceptional cycling stability after 500 cycles and high capacity under the sulfur loading of 10.53 mg cm-2 . In particular, an Ah-level Li-S pouch cell is fabricated, further demonstrating that the synthetic strategy based on atomic-level design offers a promising route toward practical high-energy-density Li-S batteries.

Single-Image-Based Deep Learning for Segmentation of Early Esophageal Cancer Lesions.

Accurate segmentation of lesions is crucial for diagnosis and treatment of early esophageal cancer (EEC). However, neither traditional nor deep learning-based methods up to today can meet the clinical requirements, with the mean Dice score - the most important metric in medical image analysis - hardly exceeding 0.75. In this paper, we present a novel deep learning approach for segmenting EEC lesions. Our method stands out for its uniqueness, as it relies solely on a single input image from a patient, forming the so-called "You-Only-Have-One" (YOHO) framework. On one hand, this "one-image-one-network" learning ensures complete patient privacy as it does not use any images from other patients as the training data. On the other hand, it avoids nearly all generalization-related problems since each trained network is applied only to the same input image itself. In particular, we can push the training to "over-fitting" as much as possible to increase the segmentation accuracy. Our technical details include an interaction with clinical doctors to utilize their expertise, a geometry-based data augmentation over a single lesion image to generate the training dataset (the biggest novelty), and an edge-enhanced UNet. We have evaluated YOHO over an EEC dataset collected by ourselves and achieved a mean Dice score of 0.888, which is much higher as compared to the existing deep-learning methods, thus representing a significant advance toward clinical applications. The code and dataset are available at: https://github.com/lhaippp/YOHO.

The influence of hydrocarbon generation on the sealing capability of mudstone caprock rich in organic matter.

To investigate the sealing capability of mudstone caprock during the evolution of organic matter (OM)-rich mudstone, a series of hydrous pyrolysis experiments were first conducted to examine the impact of hydrocarbon generation. The pore type, pore structure, porosity, and gas breakthrough pressure of pyrolytic residual samples were analyzed by field emission scanning electron microscopy, low pressure nitrogen adsorption measurements, porosimetry, and gas breakout core experiments. To model the environment at different depths, these six experiments on hydrous pyrolysis were performed at different temperatures, lithostatic pressures, and hydrodynamic pressures, while other experimental factors such as the original sample, heating time, and rate were kept constant. The results showed that during the thermal evolution process, hydrocarbons were generated from OM in mudstone, resulting in the formation of pores within the OM. Organic acids produced by hydrocarbon generation effectively dissolved minerals, leading to the creation of numerous dissolution pores. Changes in pore type led to changes in pore structure and porosity. The volume of micropores and macropores showed an increasing trend before reaching a Ro value of 1.41%. However, after passing this threshold, they began to decrease. The volume of mesopores showed a decreasing trend before reaching a Ro value of 1.32%. After 1.32%, they began to increase. The porosity was mainly affected by the pore volumes of the mesopores and macropores. The porosity exhibited two peaks: the first occurred at a Ro value of 0.72%, with a porosity level of 4.6%. The second occurred at a Ro value of 1.41% and a porosity level of 10.3%. The breakthrough pressure was a comprehensive reflection of these influences, and its trend exhibited a negative correlation with porosity (R2 = 0.886). For two high values of porosity, the breakthrough pressure corresponded to two low values. Smaller values of the breakthrough pressure indicated a poorer sealing capability of the mudstone caprock. Overall, hydrocarbon generation in the mudstone affected the sealing capability. The mudstone in the studied area exhibited good sealing at Ro below 1.32%. However, once above the 1.32% threshold, the fluctuations of the breakthrough pressure values exhibited considerable variability, requiring a comprehensive evaluation to assess its sealing capability.

Codon usage bias analysis of the spike protein of human coronavirus 229E and its host adaptability.

Human coronavirus 229E (HCoV-229E) represents one of the known coronaviruses capable of infecting humans and causes mild respiratory symptoms. It is also considered to have a zoonotic source, originating from animals and being transmitted the humans. In this study, a comprehensive phylogenetic and codon usage analysis of the spike (S) gene of HCoV-229E was conducted. Utilizing phylogenetic analysis and principal component analysis, HCoV-229E was categorized into four distinct clusters, each demonstrating unique host affiliations. Furthermore, it was observed that the codon usage bias within the S gene of HCoV-229E is relatively low, primarily influenced by natural selection patterns, with contributions from mutation pressure and dinucleotide abundance. Comparative analysis involving Codon Adaptation Index (CAI) and Relative Codon Deoptimization Index (RCDI) revealed that the codon usage pattern of HCoV-229E mirrors more closely that of camels, as opposed to alpacas and humans. The elucidation of the codon usage pattern within HCoV-229E, which we have meticulously examined, offers valuable insights for a more comprehensive comprehension of viral features, history, and evolutionary trajectory.

Toxicity of chromium to wheat (Triticum aestivum L.) in two soils: influence of soil properties and chromium form.

The toxicity of Cr to plants depends on Cr form and soil properties. Currently, the phytotoxicity differences of Cr(VI) and Cr(III) in different soils are not clear. In this study, the toxicity of Cr(VI) and Cr(III) to root growth and root morphology of wheat (Triticum aestivum L.) were compared in Shandong fluvo-aquic soil (SD soil) and Jiangxi red soil (JX soil) that is differing in soil properties. The toxicity thresholds of Cr(VI) and Cr(III) on wheat root elongation were determined by fitting the dose-effect curves. Results showed that the 10% and 50% root length inhibitory concentrations (EC10 and EC50) of Cr(III) were 53.1 and 125 times of Cr(VI) in SD soil and 8.11 and 1.36 times of Cr(VI) in JX soil, indicating that Cr(VI) was more toxic to wheat roots than Cr(III) in both soils and the toxicity discrepancy of the two forms of Cr was more prominent in SD soil. Cr(VI) exhibited higher toxicity in SD soil (alkaline) than in JX soil (acidic), whereas Cr(III) showed the opposite pattern. In addition, the ethylene diamine tetraacetic acid extractable Cr (EDTA-Cr) concentrations in soils were correlated well with the relative wheat root elongation (R2=0.854, P<0.01), indicating that soil EDTA-Cr concentration can be used as a predictor of Cr phytotoxicity. Both Cr(VI) and Cr(III) showed significant biphasic dose effects on wheat root morphology (root length, root surface area, root volume, and root tip number) in JX soil. These findings are helpful for the risk evaluation of Cr contamination in agricultural soils.

Genomic inference of a severe human bottleneck during the Early to Middle Pleistocene transition.

Population size history is essential for studying human evolution. However, ancient population size history during the Pleistocene is notoriously difficult to unravel. In this study, we developed a fast infinitesimal time coalescent process (FitCoal) to circumvent this difficulty and calculated the composite likelihood for present-day human genomic sequences of 3154 individuals. Results showed that human ancestors went through a severe population bottleneck with about 1280 breeding individuals between around 930,000 and 813,000 years ago. The bottleneck lasted for about 117,000 years and brought human ancestors close to extinction. This bottleneck is congruent with a substantial chronological gap in the available African and Eurasian fossil record. Our results provide new insights into our ancestry and suggest a coincident speciation event.

Enhancing the Mechanical Stability of 2D Fullerene with a Graphene Substrate and Encapsulation.

Recent advancements have led to the synthesis of novel monolayer 2D carbon structures, namely quasi-hexagonal-phase fullerene (qHPC60) and quasi-tetragonal-phase fullerene (qTPC60). Particularly, qHPC60 exhibits a promising medium band gap of approximately 1.6 eV, making it an attractive candidate for semiconductor devices. In this study, we conducted comprehensive molecular dynamics simulations to investigate the mechanical stability of 2D fullerene when placed on a graphene substrate and encapsulated within it. Graphene, renowned for its exceptional tensile strength, was chosen as the substrate and encapsulation material. We compared the mechanical behaviors of qHPC60 and qTPC60, examined the influence of cracks on their mechanical properties, and analyzed the internal stress experienced during and after fracture. Our findings reveal that the mechanical reliability of 2D fullerene can be significantly improved by encapsulating it with graphene, particularly strengthening the cracked regions. The estimated elastic modulus increased from 191.6 (qHPC60) and 134.7 GPa (qTPC60) to 531.4 and 504.1 GPa, respectively. Moreover, we observed that defects on the C60 layer had a negligible impact on the deterioration of the mechanical properties. This research provides valuable insights into enhancing the mechanical properties of 2D fullerene through graphene substrates or encapsulation, thereby holding promising implications for future applications.

A Noncoding A-to-U Kozak Site Change Related to the High Transmissibility of Alpha, Delta, and Omicron VOCs.

Three prevalent SARS-CoV-2 variants of concern (VOCs) emerged and caused epidemic waves. It is essential to uncover advantageous mutations that cause the high transmissibility of VOCs. However, viral mutations are tightly linked, so traditional population genetic methods, including machine learning-based methods, cannot reliably detect mutations conferring a fitness advantage. In this study, we developed an approach based on the sequential occurrence order of mutations and the accelerated furcation rate in the pandemic-scale phylogenomic tree. We analyzed 3,777,753 high-quality SARS-CoV-2 genomic sequences and the epidemiology metadata using the Coronavirus GenBrowser. We found that two noncoding mutations at the same position (g.a28271-/u) may be crucial to the high transmissibility of Alpha, Delta, and Omicron VOCs although the noncoding mutations alone cannot increase viral transmissibility. Both mutations cause an A-to-U change at the core position -3 of the Kozak sequence of the N gene and significantly reduce the protein expression ratio of ORF9b to N. Using a convergent evolutionary analysis, we found that g.a28271-/u, S:p.P681H/R, and N:p.R203K/M occur independently on three VOC lineages, suggesting that coordinated changes of S, N, and ORF9b proteins are crucial to high viral transmissibility. Our results provide new insights into high viral transmissibility co-modulated by advantageous noncoding and nonsynonymous changes.