Electrochemical one-pot cascade synthesis of thio(seleno)cyanato-substituted thiazolidine-2-imines without external electrolyte.

A novel synthetic method has been developed for generating thio(seleno)cyanato-substituted thiazolidine-2-imines via an electrochemical one-pot cascade reaction. This reaction employs isothiocyanates, N-2-en-1-amines, and KSCN (or KSeCN) under mild conditions, obviating the need for metals, chemical oxidants, and external electrolytes. The protocol is effective with unactivated alkenes and facilitates the synthesis of five- and six-membered thio(seleno)cyanato-substituted thiazolidine-2-imines. The versatility is demonstrated by its straightforward operation and scalability to gram-scale production, underscoring its potential for broader application.

Planar Chiral Charge-Transfer Cyclophanes: Convenient Synthesis, Circularly Polarized Light-Responsive Photothermal Conversion and Supramolecular Chiral Assembly.

We report herein a series of macrocycles in which the densely π-stacked charge-transfer (CT) donor/acceptor with naphthalenediimides (NDIs) or perylene diimide (PDI) as acceptor moiety pairing various donor moieties are locked by covalent bond. The X-ray crystallography of C8BDT-NDI reveals a short intramolecular π-stacking distance around 3.4 Å and the existence of intermolecular donor/acceptor π-stacking (3.7 Å). The intramolecular CT is highly dependent on the electron-donating ability of donor moiety and replacing carbazole (C8KZ) with benzo[1,2-b:4,5-b']dithiophene (C8BDT) or dihydroindolo[3,2-b]indole (C8DN) redshift CT absorption into NIR region. Notably, both C8BDT-NDI and C8DN-NDI demonstrate excellent photothermal performance, which is a result of the active non-radiative pathways. Interestingly, the different molecular symmetry between donor and acceptor moiety endows C8BDT-NDI and C8DN-NDI with intrinsic planar chirality. The enantiomeric C8BDT-NDI shows chiral selectivity for incident light, i.e., when irradiated by left-circularly polarized light, (R)-C8BDT-NDI is more sensitive and a higher maximum stable temperature is achieved. While, enantiomeric C8DN-NDI pack with different orientations forming M- and P-handedness helix, respectively, demonstrating molecular planar chirality being transferred and amplified through molecular assembly. These results provide insight into the intramolecular charge transfer in enforced D/A π-stacks in which CT interactions and planar chirality would be engineered through structural control.

Spatial patterns and driving factors of plant diversity along the urban-rural gradient in the context of urbanization in Zhengzhou, China.

Plant diversity is the basis for human survival and development, directly affecting the function and stability of urban ecosystems. Its distribution pattern and causes have been a central issue in ecological and landscape gardening research. Rapid urbanization in Zhengzhou City has led to the fragmentation of urban green spaces and damage to ecosystems, seriously affecting urban biodiversity conservation. Understanding the distribution pattern of plant diversity in the region and its relationship with environmental factors is crucial for maintaining and enhancing urban plant diversity. Plant data from 178 sample plots in the built-up area of Zhengzhou City were collected and combined with environmental factors, and the characteristics of plant diversity, richness patterns, and their main environmental explanations in Zhengzhou City were explored. Results showed that there were 596 plant species belonging to 357 genera and 110 families in the study area. There were five dominant families and four dominant genera. Four distinct spatial patterns of plant diversity were identified along the urban-rural gradient. Urbanization factors such as GDP per capita, house prices, and imperviousness within 500 m from the patch significantly influenced plant diversity. There was an imbalance between the spatial pattern of plant diversity and application of urban landscape greening in Zhengzhou City. Future studies should focus on the application of native plants, curb plant homogenization, and reduce anthropogenic interference, which are conducive to protecting and enhancing urban plant diversity. These results can provide a basis for understanding the distribution pattern and influence mechanism of urbanization factors on plant diversity and serve as a reference for policymakers and planners of plant diversity conservation in Zhengzhou City.

Identification of molecular subtypes, prognostic status and immunotherapy response in cervical cancer based on angiogenic signature genes.

Background: Cervical cancer, as one of the most common malignancies in women, is closely related to the mechanism of angiogenesis, which needs further exploration. Methods: The squamous cell carcinoma of the cervix and cervical adenocarcinoma (CESC) data from The Cancer Genome Atlas (TCGA) database. CESC subtypes based on 48 angiogenesis-related genes were identified using consistent cluster analysis, and the limma package were adopted to screen the differentially expressed genes (DEGs) associated with prognosis. Further compress the DEGs through univariate and Least Absolute Shrinkage and Selection Operator (LASSO) COX analysis to identify the key genes. Calculate immune scores using the GSVA package and predict immunotherapy response with TIDE. For in vitro analysis, the expressions of these key genes were additionally tested via reverse-transcription quantitative PCR, and the migration and invasion of Hela cells were determined in scratch and transwell assays, respectively. Results: 3 CESC subtypes were identified, with the best survival advantage in the C2 subtype and the worst in C1 subtype. A risk model was established utilizing seven key genes (MMP3, DLL4, CAP2, PDIA6, TCN2, PAPSS2, and VCAM1), showcases an Area Under the Curve (AUC) exceeding 0.7, underlining its robust performance. The risk score model showed a trend of poorer survival for patients in the high-risk score group and good agreement across different datasets. A nomogram was constructed, and calibration curves indicated robust predictive performance. Immunological analysis revealed heightened sensitivity to immunotherapy in the low-risk group. Besides, the elevated expressions of all 7 genes were seen in Hela cells, and the specific target-mediated DLL4 knockdown diminished the migration and invasion of Hela cells in vitro. Conclusion: This research provides fresh insights and a valuable tool to guide therapeutic decision-making for CESC.

Genetic diversity of Bartonella species in small mammals in the Qinghai Menyuan section of Qilian Mountain National Park, China.

Bartonella are vector-borne gram-negative facultative intracellular bacteria that can infect a wide spectrum of mammals, and are recognized as emerging human pathogens. This study aimed to investigate the prevalence and molecular characteristics of Bartonella infections in small mammals within the Qinghai Menyuan section of Qilian Mountain National Park, China. Small mammals were captured, and the liver, spleen and kidney were collected for Bartonella detection and identification using a combination of real-time PCR targeting the transfer-mRNA (ssrA) gene and followed by sequencing of the citrate synthase (gltA) gene. A total of 52 rodents were captured, and 36 rodents were positive for Bartonella, with a positivity rate of 69.23% (36/52). Bartonella was detected in Cricetulus longicaudatus, Microtus oeconomus, Mus musculus, and Ochotona cansus. The positivity rate was significantly different in the different habitats. Two Bartonella species were observed, including Bartonella grahamii and Bartonella heixiaziensis, and B. grahamii was the dominant epidemic strain in this area. Phylogenetic analysis showed that B. grahamii mainly clustered into two clusters, which were closely related to the Apodemus isolates from China and Japan and the local plateau pika isolates, respectively. In addition, genetic polymorphism analysis showed that B. grahamii had high genetic diversity, and its haplotype had certain regional differences and host specificity. Overall, high prevalence of Bartonella in small mammals in the Qinghai Menyuan section of Qilian Mountain National Park. B. grahamii is the dominant strain with high genetic diversity and potential pathogenicity to humans, and corresponding control measures should be considered.

Establishment and characterization of SSI cell line from Sebastes schlegelii intestine for investigating the immune response to Pathogenic Bacteria.

As a commercially valuable fish species, Sebastes schlegelii faces threats from pathogenic bacteria like Edwardsiella piscicida during aquaculture. The global host range of E. piscicida encompasses various species, yet its pathogenic mechanism remains incompletely elucidated. Cell lines offer invaluable in vitro resources for studying the pathogen pathogenicity. Here, we established and characterized a cell line derived from the intestinal tissue of the S. schlegelii, designated as SSI. SSI has undergone continuous subculturing for over 80 passages, demonstrating robust growth in DMEM supplemented with 10%-20% FBS and 20 µM HEPES at 24°C. Karyotype analysis and 18S rRNA amplification confirm its origin. SSI exhibits high transfection efficiency for exogenous DNA, making it suitable for gene expression and intestinal function analysis. E. piscicida infects SSI cells at low densities without inducing morphological changes within 6 h of infection, suggesting the potential of SSI as an in vitro model for studying E. piscicida pathogenicity. This cell line provides a valuable tool for investigating mucosal immunity and E. piscicida pathogenic mechanisms in marine fish.

Effects of moderate-intensity aerobic training on cardiac structure and function in type 2 mellitus diabetic rats: Based on echocardiography and speckle tracking.

PURPOSE: The present study aimed to evaluate the cardiac function changes using Layer-specific Speckle-tracking echocardiography (LS-STE) induced by Moderate-intensity aerobic training (MIAT) in Type 2 diabetes mellitus (T2DM) rats. METHODS: Twenty-six rats were divided into four groups: the Control group (Con), the Training control group (CT), the T2DM group (DM), and the T2DM training group (DT). The CT and DT groups underwent an 8 weeks MIAT. Cardiac structure and function were evaluated by echocardiography and LS-STE. RESULTS: Compared with the Con group, left atrial diameter (LAD), left ventricular end-diastolic diameter(LVEDD), relation wall thickness (RWT), and left ventricular mass (LVM) were significantly higher, and the endo-, mid-, and epi-longitudinal strain (LS), global radial strain (GRS), and endo- and mid-circumferential strain (CS) were significantly lower in DM rats (all p < 0.05). The endo-, mid-, and epi-LS, GRS, endo- and mid-CS were increased in DT rats compared with DM rats (all p < 0.05). Compared with Con rats, CT rats had a significant increase in LVEDD and LVM (all p < 0.05), meanwhile myocardial strains had no significant differences (all p > 0.05). CONCLUSION: LS-STE was a sensitive method to assess subclinical myocardial changes in T2DM rats. MIAT had the benefit of reversing cardiac systolic subclinical dysfunction in T2DM rats.

miR-24-3p inhibits lipid synthesis and progesterone secretion in chicken granulosa cells via ERK1/2 signaling pathway.

Normal follicular development is the basis for ovulation in poultry. Our previous sequencing analysis revealed a high expression of miR-24-3p in chicken follicles from degenerated ovaries, suggesting that miR-24-3p may modulate follicular development. Hence, this study investigated the specific mechanisms of miR-24-3p in regulating chicken follicular development. The results revealed that the proliferation, lipid synthesis, and progesterone secretion were significantly inhibited after miR-24-3p overexpression in chicken granulosa cells, vice versa by miR-24-3p knockdown. Dual-specificity phosphatase 16 (DUSP16) and thousand and one amino acid kinase 1 (TAOK1) were identified as potential target genes of miR-24-3p. Further validation revealed that knockdown of DUSP16 and TAOK1 suppressed proliferation, lipid synthesis, and progesterone secretion in chicken granulosa cells. Moreover, we observed that miR-24-3p, along with knockdown of DUSP16 and TAOK1, increased the phosphorylation levels of extracellular signal-regulated kinases 1 and 2 (ERK1/2). Our previous study proved that activation of ERK1/2 inhibited lipid synthesis and progesterone secretion of chicken granulosa cells. In summary, we demonstrated that miR-24-3p targeting DUSP16 and TAOK1 disrupts lipid synthesis and progesterone secretion via ERK1/2 signaling pathway in chicken granulosa cells in vitro. These results may provide a new theoretical basis for resolving miRNAs regulation on reproductive performance of chickens.

A photoactivated chiral molecular clamp rotated by selective anion binding.

Developing chiral molecular platforms that respond to external fields provides opportunities for designing smart chiroptical materials. Herein, we introduce a molecular clamp whose chiral properties can be turned on by photoactivation. Selective anion binding achieves rational tuning of the conformations and chiroptical properties of the clamp, including circular dichroism and circularly polarized luminescence. Cyanostilbene segments were conjugated to chiral amines with a rotatable axis. Negligible chiroptical signals were significantly enhanced through a light illumination-induced isomerization. Binding with halide ions (F-, Cl- and Br-) enables chiroptical inversion and subsequent amplification of the resulting opposite handedness state by photo treatment. In contrast, the larger I- and NO3 - ions failed to achieve chiroptical inversion. Also the handedness inversion was hampered in conformationally locked amines. Density-functional theory-based computational studies and experimental results reveal a structural transformation that proceeds from a butterfly-like open geometry to a closed V-shaped state initiated by four hydrogen bonds and the rotatable axis. This work illustrates design protocols for use in smart chiroptical molecular platforms mediated by photo treatment and anion binding.

Interactive effect between transcranial focused ultrasound and transcranial magnetic stimulation on human motor cortex.

OBJECTIVE: Transcranial focused ultrasound (TUS) can suppress human motor cortical excitability. However, it is unclear whether the TUS may interact with transcranial magnetic stimulation (TMS) when they co-delivered in multiple trials. METHODS: Nineteen subjects received three different TUS-TMS co-stimulation protocols to the motor cortex including concurrent stimulation (TUS-TMS-C), separated stimulation (TUS-TMS-S), and TMS only. In each condition, two runs of 30 stimulation trials were conducted with a five-minute rest between runs. Motor-evoked potentials (MEP) were recorded during stimulation and at 0, 10, 20, and 30 min after stimulation. The MEP amplitudes after intervention were normalized to the mean pre-intervention MEP amplitude and expressed as MEP ratios. An additional test with TUS alone was applied to all participants to assess whether TUS itself can elicit after-effects. RESULTS: There were no significant after-effects of all three interventions on MEP ratios. However, 11 subjects who showed online inhibition (OI + ) during the TUS-TMS-C protocol, defined as having MEP ratio less than 1 during TUS-TMS-C, showed significant MEP suppression at 10, 20 and 30 min after TUS-TMS-C. In 8 subjects did not show online inhibition (OI-), defined as having MEP ratios greater than 1 during TUS-TMS-C, showed no significant inhibitory after-effects. OI + and OI- status did not change in a follow-up repeat TUS-TMS-C test. TUS alone did not generate inhibitory after-effects in either OI + or OI- participants. CONCLUSIONS: Our results showed that co-delivery of TUS and TMS can elicit inhibitory after-effect in subjects who showed online inhibition, suggesting that TUS and TMS may interact with each other to produce plasticity effects. SIGNIFICANCE: TUS and TMS may interact with each other to modulate cortical excitability.

An Objective Injury Threshold for the Maximum Principal Strain Criterion for Brain Tissue in the Finite Element Head Model and Its Application.

Although the finite element head model (FEHM) has been widely utilized to analyze injury locations and patterns in traumatic brain injury, significant controversy persists regarding the selection of a mechanical injury variable and its corresponding threshold. This paper aims to determine an objective injury threshold for maximum principal strain (MPS) through a novel data-driven method, and to validate and apply it. We extract the peak responses from all elements across 100 head impact simulations to form a dataset, and then determine the objective injury threshold by analyzing the relationship between the combined injury degree and the threshold according to the stationary value principle. Using an occipital impact case from a clinical report as an example, we evaluate the accuracy of the injury prediction based on the new threshold. The results show that the injury area predicted by finite element analysis closely matches the main injury area observed in CT images, without the issue of over- or underestimating the injury due to an unreasonable threshold. Furthermore, by applying this threshold to the finite element analysis of designed occipital impacts, we observe, for the first time, supra-tentorium cerebelli injury, which is related to visual memory impairment. This discovery may indicate the biomechanical mechanism of visual memory impairment after occipital impacts reported in clinical cases.

Research Progress on the Regulating Factors of Muscle Fiber Heterogeneity in Livestock: A Review.

The type of muscle fiber plays a crucial role in the growth, development, and dynamic plasticity of animals' skeletal muscle. Additionally, it is a primary determinant of the quality of both fresh and processed meat. Therefore, understanding the regulatory factors that contribute to muscle fibers' heterogeneity is of paramount importance. Recent advances in sequencing and omics technologies have enabled comprehensive cross-verification of research on the factors affecting the types of muscle fiber across multiple levels, including the genome, transcriptome, proteome, and metabolome. These advancements have facilitated deeper exploration into the related biological questions. This review focused on the impact of individual characteristics, feeding patterns, and genetic regulation on the proportion and interconversion of different muscle fibers. The findings indicated that individual characteristics and feeding patterns significantly influence the type of muscle fiber, which can effectively enhance the type and distribution of muscle fibers in livestock. Furthermore, non-coding RNA, genes and signaling pathways between complicated regulatory mechanisms and interactions have a certain degree of impact on muscle fibers' heterogeneity. This, in turn, changes muscle fiber profile in living animals through genetic selection or environmental factors, and has the potential to modulate the quality of fresh meat. Collectively, we briefly reviewed the structure of skeletal muscle tissue and then attempted to review the inevitable connection between the quality of fresh meat and the type of muscle fiber, with particular attention to potential events involved in regulating muscle fibers' heterogeneity.

Method for fabricating circular polarization beam splitters based on polarization holography.

Based on polarization holography, circular polarization beam splitters with separation angles of up to 100° have been fabricated. The left- and right-handed circularly polarized waves can be reconstructed by the two holograms that were designed by the tensor theory of polarization holography, respectively. In the fabrication of circular polarization beam splitters, two holograms were recorded only by the interference method in the same area of the polarization-sensitive material. This method is simple, inexpensive, and easy to adjust the separation angles and element size. The diffraction efficiency and the polarization state of the reconstructed waves were tested under different incident waves, and the experimental results are in good agreement with the theory. This work not only deepens our understanding of polarization holography but also expands the applications of polarization holography.

A high-performance electrochemical sensor based on dendritic Au/Zn modified carbon cloth for the determination of nitrite in aquaculture.

Nitrite is a common nitrogen-containing compound that possesses high biological toxicity, thereby posing a serious threat to aquatic organisms. Therefore, it is imperative to develop a rapid and quantitative determination approach for nitrite. In this study, the aim was to prepare a novel electrochemical sensor to determine nitrite. This was achieved by synthesizing Au/Zn dendritic complexes on a carbon cloth self-supported electrode after plasma treated by a stepwise strategy of electrodeposition and in-situ corrosion. In accordance with the optimal experimental conditions, the electrode exhibited remarkable catalytic activity for the electrooxidation of nitrite ions (pH = 8.0), accompanied by a considerable enhancement in peak anodic current in comparison to the unmodified electrode. The sensor exhibited a wide linear range (1-833 µM, 833-8330 µM), high sensitivity (3506 µA mM-1 cm-2, 538 µA mM-1 cm-2), a low detection limit (0.43 µM), and excellent selectivity, reproducibility, and stability for the determination of nitrite. Furthermore, the prepared sensor was successfully applied to the detection of nitrite in tap water, fish holding pond water and duck pond water, demonstrating good recovery and no significant difference from the spectrophotometric results. The results suggest that the electrochemical sensor developed in this study represents a straightforward yet efficacious approach to the development of advanced portable sensors for aquaculture applications.

Exercise Volume Provides New Insight into the Effects of Housing Systems on Chicken Body Conformation, Carcass Traits, Meat Quality, and Serum Biochemical Parameters.

This study aims to investigate the dynamic changes in daily step counts under different housing systems and further explore the effects of housing system on the body conformation, carcass traits, meat quality, and serum biochemical parameters of a Chinese indigenous chicken breed. At 60 d of age, 300 Jiuyuan Black male chickens with similar body weights in each housing system were further raised until the age of 150 d. At 90, 120, and 150 d of age, in both cage-reared and free-range systems, the top 20 chickens with the highest step counts measured using pedometers and the bottom 20 chickens with the lowest step counts were designated as the cage high-steps group (CHS), the cage low-steps group (CLS), the free-range high-steps group (FHS), and the free-range low-steps group (FLS), respectively. The results show that, at any age stage, the average daily steps (ADS) and total steps (TS) of the FHS group are significantly higher than the other three groups (p < 0.05). The TS of almost all groups showed an overall downward trend as the age increased. Increased exercise volume results in reduced shank length (90 d), breast width (90 d), and keel length (150 d) (p < 0.05). Only birds at 90 d of age from the FHS and FLS groups exhibited lower live body weight, carcass weight, half-eviscerated weight, eviscerated weight, breast muscle weight, leg muscle weight, and percentage of eviscerated weight than the CLS group (p < 0.05). Birds from the FHS group showed the highest heart weight values but the lowest abdominal fat weight values among these four groups (p < 0.05). Both the breast and leg muscle samples from the FHS group displayed higher dry matter and shear force than those from the CHS and CLS groups (p < 0.05). The FHS group displayed the lowest intramuscular fat among the four groups (p < 0.05). The creatine kinase (CK) and lactate dehydrogenase (LDH) levels in chickens of all age stages were almost observed to rise with increased physical activity. In conclusion, free-range chickens with more exercise volume exhibited an elevated heart weight and reduced abdominal fat but showed negative effects on some body measurements and carcass traits. These results can provide a theoretical basis for the selection of different housing systems for Chinese indigenous chickens.

Multiple unfolded protein response pathways cooperate to link cytosolic dsDNA release to stimulator of interferon gene activation.

The double-stranded DNA (dsDNA) sensor STING has been increasingly implicated in responses to "sterile" endogenous threats and pathogens without nominal DNA or cyclic di-nucleotide stimuli. Previous work showed an endoplasmic reticulum (ER) stress response, known as the unfolded protein response (UPR), activates STING. Herein, we sought to determine if ER stress generated a STING ligand, and to identify the UPR pathways involved. Induction of IFN-ß expression following stimulation with the UPR inducer thapsigargin (TPG) or oxygen glucose deprivation required both STING and the dsDNA-sensing cyclic GMP-AMP synthase (cGAS). Furthermore, TPG increased cytosolic mitochondrial DNA, and immunofluorescence visualized dsDNA punctae in murine and human cells, providing a cGAS stimulus. N-acetylcysteine decreased IFN-ß induction by TPG, implicating reactive oxygen species (ROS). However, mitoTEMPO, a mitochondrial oxidative stress inhibitor did not impact TPG-induced IFN. On the other hand, inhibiting the inositol requiring enzyme 1 (IRE1) ER stress sensor and its target transcription factor XBP1 decreased the generation of cytosolic dsDNA. iNOS upregulation was XBP1-dependent, and an iNOS inhibitor decreased cytosolic dsDNA and IFN-ß, implicating ROS downstream of the IRE1-XBP1 pathway. Inhibition of the PKR-like ER kinase (PERK) pathway also attenuated cytoplasmic dsDNA release. The PERK-regulated apoptotic factor Bim was required for both dsDNA release and IFN-ß mRNA induction. Finally, XBP1 and PERK pathways contributed to cytosolic dsDNA release and IFN-induction by the RNA virus, Vesicular Stomatitis Virus (VSV). Together, our findings suggest that ER stressors, including viral pathogens without nominal STING or cGAS ligands such as RNA viruses, trigger multiple canonical UPR pathways that cooperate to activate STING and downstream IFN-ß via mitochondrial dsDNA release.

Integrative analysis of RNA-seq and Ribo-seq reveals that lncRNA-GRN regulates chicken follicular atresia through miR-103-3p/FBXW7 axis and encoding peptide.

Follicular atresia in chickens seriously reduced the egg production and economic benefits of chickens. LncRNA plays a key role in the process of follicular atresia. In this study, RNA-seq and Ribo-seq were performed on normal and atretic follicles of Dahen broilers to screen out lncRNAs that may regulate follicle atresia, and to study the molecular mechanisms of their regulation. GRN granulin precursor (lncGRN, ID: 101748909) was highly expressed in atretic follicles with translational ability. A molecular regulatory network of lncGRN/miR-103-3p/FBXW7 was constructed through bioinformatics analysis and dual luciferase reporting. LncGRN promoted the expression of FBXW7 by adsorption of miR-103-3p, thereby inhibiting the proliferation of chicken granulosa cells (GCs), promoting apoptosis of chicken GCs and inhibiting steroid hormone synthesis thus induced follicular atresia. Meanwhile, we also found a micropeptide named GRN-122aa derived by lncGRN which can promote follicular atresia. In conclusion, our study found that lncGRN promoted follicular atresia through the lncGRN/miR-103-3p/FBXW7 axis and the translation micropeptide GRN-122aa. This study provided new insight into the post-transcriptional regulation mechanism of lncGRN suggesting that lncGRN may act as a potential to regulate chicken follicle development, and provided a theoretical argument for further improving the egg production of chickens through molecular breeding.

Discovery of SARS-CoV-2 papain-like protease (PLpro) inhibitors with efficacy in a murine infection model.

Vaccines and first-generation antiviral therapeutics have provided important protection against COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a need for additional therapeutic options that provide enhanced efficacy and protection against potential viral resistance. The SARS-CoV-2 papain-like protease (PLpro) is one of the two essential cysteine proteases involved in viral replication. While inhibitors of the SARS-CoV-2 main protease have demonstrated clinical efficacy, known PLpro inhibitors have, to date, lacked the inhibitory potency and requisite pharmacokinetics to demonstrate that targeting PLpro translates to in vivo efficacy in a preclinical setting. Here, we report the machine learning-driven discovery of potent, selective, and orally available SARS-CoV-2 PLpro inhibitors, with lead compound PF-07957472 (4) providing robust efficacy in a mouse-adapted model of COVID-19 infection.

Prevalence and molecular detection of Babesia microti in rodents in Southeastern Shanxi, China.

Babesia is a tick-transmitted parasite that infects wild and domestic animals, causes babesiosis in humans, and is an increasing public health concern. Here, we investigated the prevalence and molecular characteristics of Babesia infections in the rodents in Southeastern Shanxi, China. Small rodents were captured, and the liver and spleen tissues were used for Babesia detection using traditional PCR and sequencing of the partial 18S rRNA gene. The analysis revealed that 27 of 252 small rodents were positive for Babesia, with an infection rate of 10.71%. The infection rates in different sexes and rodent tissues were not statistically different, but those in different rodent species, habitats, and sampling sites were statistically different. The highest risk of Babesia infection was observed in Niviventer confucianus captured from the forests in Huguan County. Forty-three sequences from 27 small rodents positive for Babesia infection were identified as Babesia microti, including 42 sequences from 26 N. confucianus, and one sequence from Apodemus agrarius. Phylogenetic analysis showed that all sequences were clustered together and had the closest genetic relationship with Babesia microti strains isolated from Rattus losea and N. confucianus in China, and belonged to the Kobe-type, which is pathogenic to humans. Compared to other Kobe-type strains based on the nearly complete 18S rRNA gene, the sequences obtained in this study showed the difference by 1-3 bp. Overall, a high prevalence of Babesia microti infection was observed in small rodents in Southeastern Shanxi, China, which could benefit us to take the implementation of relevant prevention and control measures in this area.

[Expression and clinical significance of serum squamous cell carcinoma antigen（SCCAg） in sinonasal inverted papilloma].

Objective:To compare the expression levels of SCCAg in inverted papilloma of the nasal sinuses and other sinuses and sinus masses. To investigate the correlation between the expression of SCCAg in sinonasal inverted papilloma and outcome. Methods:Sixty-eight patients with unilateral nasal and sinus masses admitted to the Otorhinolaryngology Center of the Affiliated Hospital of Guangdong Medical University from September 2020 to February 2023 were randomly selected, including 31 patients with inverted papilloma （experimental group） and 37 patients with unilateral nasal and sinus masses excluding inverted papilloma （control group）. The application of automatic chemiluminescence immunoassay to test the serum SCCAg of the experimental group before surgery and 1 week after surgery, and the control group to measure the serum SCCAg before surgery. Clinical data were also collected. Results:There was no significant difference between the experimental group and the control group in gender and preoperative peripheral blood inflammatory indicators. However, there was significant difference in age and preoperative serum SCCAg level（P<0.001）. The serum SCCAg levels of the experimental group before and 1 week after surgery were significantly different（P<0.001）. The positive predictive value, negative predictive value, sensitivity and specificity of serum SCCAg in the diagnosis of varus papilloma were 92.6%, 85.4%, 77.4%, 94.6% and 0.72, respectively. The effect of serum SCCAg in the diagnosis of varus papilloma was analyzed by drawing the subject's working characteristic curve, and the area under the curve was 0.968（P<0.001）. When serum SCCAg greater than 2.7 ng/mL, the sensitivity and specificity were 67.7% and 94.6%, respectively. There was statistical significance in serum SCCAg levels between patients with and without recurrence（P<0.05）. Conclusion:The level of SCCAg in unilateral nasal and sinuses tumors, excluding squamous cell carcinoma, was significantly increased in inverted papilloma. The detection of serum SCCAg can be used as a simple and cost-effective auxiliary diagnostic tool for patients with nasal inverted papilloma before operation. Significant differences in preoperative and postoperative levels can be used for preliminary evaluation of surgical efficacy. Monitoring the serum SCCAg level in patients with inverted papilloma after surgery can predict recurrence and provide a simple and feasible method for postoperative follow-up.