Circulating micrornas as potential diagnostic biomarkers for cervical intraepithelial neoplasia and cervical cancer: a systematic review and meta-analysis.

BACKGROUND: Cervical cancer is a prevalent malignancy of the female reproductive system. Cervical intraepithelial neoplasia (CIN) is a precursor lesion for CC. Various studies have examined circulating microRNAs (miRNAs) as potential early diagnostic markers for CC and CIN. However, the findings have been inconclusive. Therefore, it is necessary to evaluate the diagnostic accuracy and identify potential sources of variability among these studies. METHODS: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched to identify relevant literature. Then, Stata 14.0 was utilized to calculate summary estimates for diagnostic parameters, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (ROC). To scrutinize the heterogeneity, the Cochran-Q test and I2 statistic were utilized. As significant heterogeneity was observed, the random effects model was chosen. To explore potential sources of the heterogeneity, subgroup and regression analyses were conducted. RESULTS: We analysed 12 articles reporting on 24 studies involving 1817 patients and 1731 healthy controls. The pooled sensitivity was 0.77 (95% CI 0.73-0.81), the specificity was 0.81 (95% CI 0.73-0.86), the PLR was 3.99 (95% CI 2.81-5.65), the NLR was 0.28 (95% CI 0.23-0.35), the DOR was 14.18 (95% CI 8.47-23.73), and the area under the curve (AUC) was 0.85 (95% CI 0.81-0.87). Subgroup analysis revealed that multiple miRNAs can improve diagnostic performance; the pooled sensitivity of multiple miRNAs was 0.78 (95% CI 0.68-0.86), the specificity was 0.85 (95% CI 0.78-0.90), and the AUC was 0.89 (95% CI 0.86-0.91). CONCLUSION: This study suggested that circulating microRNAs may be biomarkers for early CC diagnosis.

Structures, functions, and regulatory networks of universal stress proteins in clinically relevant pathogenic Bacteria.

Universal stress proteins are a class of proteins widely present in bacteria, archaea, plants, and invertebrates, playing essential roles in bacterial adaptation to various environmental stresses. The functions of bacterial universal stress proteins are versatile, including resistance to oxidative stress, maintenance of cell wall integrity, DNA damage repair, regulation of cell division and growth, among others. When facing stresses such as temperature changes, pH shifts, fluctuations in oxygen concentration, and exposure to toxins, these proteins can bind to specific DNA sequences and rapidly adjust bacterial metabolic pathways and gene expression patterns to adapt to the new environment. In summary, bacterial universal stress proteins play a crucial role in bacterial adaptability and survival. A comprehensive understanding of bacterial stress response mechanisms and the development of new antibacterial strategies are of great significance. This review summarizes the research progress on the structure, function, and regulatory factors of universal stress proteins in clinically relevant bacteria, aiming to facilitate deeper investigations by clinicians and researchers into universal stress proteins.

Discovery of Unique Bis-Substituted Aromatic Amide Derivatives as Novel Highly Potent Antibiotics for Combating Methicillin-Resistant Staphylococcus aureus (MRSA).

Due to the increasing antibiotic resistance, developing novel antimicrobials to fight infections caused by resistant bacteria is imperative. Herein, a series of novel bis-substituted aromatic amides were designed and synthesized through modifying the hit compound 1, and their antimicrobial activities were evaluated. Among them, compound 4t, as the most potent lead, exhibited excellent antimicrobial activities against Gram-positive bacteria, including clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, while keeping weak hemolytic and mammalian cytotoxic activities. Furthermore, compound 4t displayed rapid bactericidal capabilities, low tendency to produce resistance, and favorable capacities to destroy bacterial biofilms. Further explorations indicated that compound 4t induces bacterial death by binding to cardiolipin (CL) on the bacterial membrane, disrupting the cell membrane, and facilitating the accumulation of reactive oxygen species (ROS). Additionally, compound 4t showed remarkable anti-MRSA activity in vivo, demonstrating compound 4t could be developed as a potential candidate to combat MRSA infections.

Surveillance of COVID-19 and influenza A(H1N1) prevalence in China via medicine-based wastewater biomarkers.

The simultaneous monitoring of individual or multiple diseases can be achieved by selecting therapeutic medicines used to treat the primary symptoms of the condition as biomarkers in wastewater. This study proposes a novel approach to monitor the prevalence of COVID-19 and influenza A (H1N1) by selecting nine medicines to serve as biomarkers, including three antipyretics, three antivirals, and three cough suppressants. To verify our approach, wastewater samples were collected from seventeen urban and five rural wastewater treatment plants (WWTPs) in a Chinese city over a period of one year. The use of antipyretics increased notably during the COVID-19 pandemic, while the consumption of antivirals for influenza A (H1N1) rose in the post-COVID-19 pandemic period, indicating a minor spike in the occurrence of influenza A (H1N1) after the COVID-19 pandemic. Fever is a significant symptom of COVID-19 and can serve as a reliable indicator of disease prevalence. Our research found that the prevalence of COVID-19 in urban areas was significantly higher (at 78.5 %, 95 % CI: 73.4 % - 83.9 %) than in rural areas (with a prevalence of 48.1 %, 95 % CI: 42.4 % - 53.8 %). The prevalence of COVID-19 in urban areas in this study was consistent with the data reported by the Chinese center for Disease Control and Prevention (82.4 %). Continuous monitoring of WWTPs in urban areas with fluctuating populations and complex demographics can provide early disease warning. Our results demonstrate the feasibility of evaluating community disease prevalence by selecting major therapeutic medicines as biomarkers in wastewater.

3D-US and CBCT Dual-guided Radiotherapy for Postoperative Uterine Malignancy: A Primary Workflow Set-up.

Introduction: The consistency of clinical target volume is essential to guiding radiotherapy with precision for postoperative uterine malignancy patients. By introducing a three-dimensional ultrasound system (3D-US) into image-guided radiation therapy (IGRT), this study was designed to investigate the initial workflow set-up, the therapeutic potential, and the adverse events of 3D-US and cone-beam computed tomography (CBCT) dual-guided radiotherapy in postoperative uterine malignancy treatment. Methods: From April 2021 to December 2021, postoperative uterine malignancy patients were instructed to follow the previously standard protocol of daily radiation treatment, particularly a 3D-US (Clarity system) guiding was involved before CBCT. Soft-tissue-based displacements resulting from the additional US-IGRT were acquired in the LT (left)/RT (right), ANT (anterior)/POST (posterior), and SUP (superior)/INF(inferior) directions of the patient before fractional treatment. Displacement distributions before and after treatment either from 3D-US or from CBCT were also estimated and compared subsequently, and the urinary and rectal toxicity was further evaluated. Results: All the patients completed radiation treatment as planned. The assessment of 170 scans resulted in a mean displacement of (0.17 ± 0.24) cm, (0.19 ± 0.23) cm, (0.22 ± 0.26) cm for bladder in LT/RT, ANT/POST, and SUP/INF directions. A mean deviation of (0.26 ± 0.22) cm, (0.58 ± 0.5) cm, and (0.3 ± 0.23) cm was also observed for the bladder centroid between the CBCT and computed tomography -simulation images in three directions. Paired comparison between these two guidance shows that the variations from 3D-US are much smaller than those from CBCT in three directions, especially in ANT/POST and SUP/INF directions with significance (P = 0.000, 0.001, respectively). During treatment, and 0, 3, 6, 9, and 12 months after treatment, there was no severe urinary and rectal toxicity happened. Conclusion: A primary workflow of 3D-US and CBCT dual-guided radiotherapy has been established, which showed great therapeutic potential with mild to moderate urinary and rectal toxicity for postoperative uterine malignancy patients. But the clinical outcomes of this non-invasive technique need to be investigated further.

Plants acquired mitochondrial linear plasmids horizontally from fungi likely during the conquest of land.

Mitochondrial linear plasmids have been sporadically reported in fungi and plants. Yet, much remains obscure about the diversity, distribution, and evolution of mitochondrial linear plasmids. Here, through phylogenomic analyses across 7,163 cellular organisms (including 991 plants), we find that mitochondrial linear plasmids are widely present in land plants and fungi. Phylogenetic analyses indicate that plants are likely to have acquired mitochondrial linear plasmids horizontally from fungi before or during the conquest of terrestrial environments by plants. Gene content analyses show that mitochondrial linear plasmids harbor a highly dynamic and promiscuous repertoire of genes. Our study refines the understanding of the origin and evolution of mitochondrial linear plasmids.

CaWRKY50 Acts as a Negative Regulator in Response to Colletotrichum scovillei Infection in Pepper.

Chili anthracnose is one of the most common and destructive fungal pathogens that affects the yield and quality of pepper. Although WRKY proteins play crucial roles in pepper resistance to a variety of pathogens, the mechanism of their resistance to anthracnose is still unknown. In this study, we found that CaWRKY50 expression was obviously induced by Colletotrichum scovillei infection and salicylic acid (SA) treatments. CaWRKY50-silencing enhanced pepper resistance to C. scovillei, while transient overexpression of CaWRKY50 in pepper increased susceptibility to C. scovillei. We further found that overexpression of CaWRKY50 in tomatoes significantly decreased resistance to C. scovillei by SA and reactive oxygen species (ROS) signaling pathways. Moreover, CaWRKY50 suppressed the expression of two SA-related genes, CaEDS1 (enhanced disease susceptibility 1) and CaSAMT1 (salicylate carboxymethyltransferase 1), by directly binding to the W-box motif in their promoters. Additionally, we demonstrated that CaWRKY50 interacts with CaWRKY42 and CaMIEL1 in the nucleus. Thus, our findings revealed that CaWRKY50 plays a negative role in pepper resistance to C. scovillei through the SA-mediated signaling pathway and the antioxidant defense system. These results provide a theoretical foundation for molecular breeding of pepper varieties resistant to anthracnose.

Origin of the OAS-RNase L innate immune pathway before the rise of jawed vertebrates via molecular tinkering.

Discriminating self from nonself is fundamental to immunity. Yet, it remains largely elusive how the mechanisms of self and nonself discrimination originated. Sensing double-stranded RNA as nonself, the 2',5'-oligoadenylate synthetase (OAS)-ribonuclease L (RNase L) pathway represents a crucial component of innate immunity. Here, we combine phylogenomic and functional analyses to show that the functional OAS-RNase L pathway likely originated through tinkering with preexisting proteins before the rise of jawed vertebrates during or before the Silurian period (444 to 419 Mya). Multiple concerted losses of OAS and RNase L occurred during the evolution of jawed vertebrates, further supporting the ancient coupling between OAS and RNase L. Moreover, both OAS and RNase L genes evolved under episodic positive selection across jawed vertebrates, suggesting a long-running evolutionary arms race between the OAS-RNase L pathway and microbes. Our findings illuminate how an innate immune pathway originated via molecular tinkering.

Novel Label-Free Nanocrystalline Gold Interdigitated Microelectrode Immunosensor for the Rapid and Ultrasensitive Detection of SARS-CoV-2.

Waves of COVID-19 outbreaks have dragged down the global economy and endangered human life. There is an urgent need for timeliness and sensitive SARS-CoV-2 detection techniques to complement the existing PCR assay. Herein, the controllable growth of gold crystalline grains was achieved by applying the reverse current during pulse electrochemical deposition (PED) interval. The proposed method validates the effects of pulse reverse current (PRC) on the atomic arrangement, crystal structures, orientations, and film characteristics in Au PED. The gap between the gold grains on the surface of the nanocrystalline gold interdigitated microelectrodes (NG-IDME) fabricated by the PED+PRC process matches the size of the antiviral antibody. Immunosensors are prepared by binding a large number of antiviral antibodies on the surface of NG-IDME. The NG-IDME immunosensor has a high specific capture ability for SARS-CoV-2 nucleocapsid protein (SARS-CoV-2/N-Pro) and completes ultrasensitive and quantification of SARS-CoV-2/N-Pro in humans and pets within 5 min (the LOQ as low as 75 fg/mL). The specificity, accuracy, stability, and actual blind sample tests show that the NG-IDME immunosensor is suitable for the detection of SARS-CoV-2 in humans and animals. This approach assists in monitoring the transmission of SARS-CoV-2-infected animals to humans.

College students' learning stress, psychological resilience and learning burnout: status quo and coping strategies.

BACKGROUND: The relationships of college students' learning stress, psychological resilience and learning burnout remain unclear. We aimed to investigate the status quo and relationship of college students' learning stress, psychological resilience and learning burnout, to provide insights to the management and nursing care of college students. METHODS: From September 1 to October 31, 2022, students in our college were selected by stratified cluster sampling and underwent survey with the learning stress scale, college students' learning burnout scale and the psychological resilience scale of college students. RESULTS: A total of 1680 college students were surveyed in this study. The score of learning burnout was positively correlated with the score of learning stress (r = 0.69), and negatively correlated with the score of psychological resilience (r = 0.59), and the score of learning stress was negatively correlated with the score of psychological resilience (r = 0.61). Learning pressure was correlated with the age(r=-0.60) and monthly family income(r=-0.56), the burnout was correlated with the monthly family income(r=-0.61), and psychological resilience was correlated with the age(r = 0.66) (all P < 0.05). Psychological resilience played an intermediary role in the prediction of learning burnout by learning stress, with an total intermediary role of-0.48, accounting for 75.94% of the total effect. CONCLUSIONS: Psychological resilience is the mediating variable of the influence of learning stress on learning burnout. College managers should take various effective measures to improve college students' psychological resilience to reduce college students' learning burnout.

GC­MSC­derived circ_0024107 promotes gastric cancer cell lymphatic metastasis via fatty acid oxidation metabolic reprogramming mediated by the miR­5572/6855­5p/CPT1A axis.

Gastric cancer tissue­derived mesenchymal stem cells (GC­MSCs) play a critical role in facilitating gastric cancer metastasis. Recently, circular RNAs (circRNAs) and metabolic reprogramming have been found to be extensively involved in the malignant progression of tumors, including gastric cancer. However, the biological role and potential mechanisms of GC­MSC­derived circRNAs in metabolic reprogramming remain elusive. Herein, the expression profiles of circRNAs and mRNAs were compared between GC­MSCs and bone marrow­derived MSCs (BM­MSCs) using microarray analysis. circ_0024107 was identified to mediate GC­MSCs to promote gastric cancer lymphatic metastasis by inducing fatty acid oxidation (FAO) metabolic reprogramming. Mechanistically, circ_0024107 served as a sponge of miR­5572 and miR­6855­5p to elicit the FAO metabolic reprograming of GC­MSCs by upregulating carnitine palmitoyltransferase 1A (CPT1A). In addition, GC­MSCs promoted metastasis which was dependent on the induction of FAO in gastric cancer cells mediated by circ_0024107. The circ_0024107/miR­5572/6855­5p/CPT1A axis was deregulated in gastric cancer tissues and GC­MSCs, and was associated with lymph node metastasis and the prognosis of patients with gastric cancer. Taken together, the findings of the present study suggest the crucial role of FAO metabolic reprogramming mediated by GC­MSC­derived circ_0024107 in synergistically promoting gastric cancer lymphatic metastasis via miR­5572/6855­5p­CPT1A signaling; this suggests that circ_0024107 may be an attractive target for gastric cancer intervention.

[Correlation analysis between imaging classification of varus knee osteoarthritis and axis angle of tibiofemoral and patellofemoral joints].

OBJECTIVE: To explore correlation between imaging classification of knee osteoarthritis (KOA) and axis angle of tibiofemoral and patellofemoral joints. METHODS: A retrospective analysis of 739 middle-aged and elderly patients with KOA (1 026 knee joints) who underwent vertical X-ray examination of both lower limbs and lateral knee joints from September 2018 to December 2020. Among them, 63 patients with K-L 0 grade (95 knee joints), 100 patients with K-L 1 grade (130 knee joints), 161 patients with K-L 2 grade (226 knee joints), 187 patients with K-L 3 grade (256 knee joints), and 228 patients of K-L 4 grade (319 knee joints). According to relative position of knee joint center and line between hip joint center and ankle joint center, the affected knee was divided into varus group(844 knees joints) and valgus group (182 knees joints). According to Install-Salvati method, the affected knee was divided into three groups, such as high patella (patella height>1.2 mm, 347 knees joints), median patella (patella height ranged from 0.8 to 1.2 mm, 561 knees joints), and low patella (patella height<0.8 mm, 118 knees joints). Lower femur angle, upper tibia angle, femoral neck shaft angle, femoral tibial angle, joint gap angle, hip-knee-ankle angle, patella-femoral angle and patella height among different groups were observed and compared. RESULTS: (1) In varus KOA group, there were statistical differnces in hip-knee-ankle angle, tibiofemoral angle, lower femoral angle, upper tibial angle, joint space angle, and femoral neck shaft angle of patients with different K-L grades (P<0.05). Hip-knee-ankle angle, tibiofemoral angle, lower femoral angle, upper tibial angle, joint space angle and K-L grade were significantly positively correlated at 0.01(P<0.05);femoral neck shaft angle and K-L grade showed negative correlation at 0.01(P<0.05). (2) In valgus KOA group, hip-knee-ankle angle, there were statistical differences in tibiofemoral angle, inferior femoral angle, superior tibial angle, joint space angle, and femoral neck shaft angle of patients with different K-L grades(P<0.05). Hip-knee-ankle angle, tibiofemoral angle, lower femoral angle, upper tibial angle, and femoral neck shaft angle showed negative correlation with K-L grades at level of 0.01 (P<0.05);joint gap angle and K-L grades showed significantly positive correlation at level of 0.01(P<0.05). (3) In high patella group, there were statistically differences in patellar height and patellar femoral angle of different K-L grades(P<0.05);there were no statistical difference in patella height and patellar femoral angle of different K-L grades in median patella group. There was no significant difference in patella heightin low patella group with different K-L grades(P>0.05), and there was statistical difference in patellofemoral angle(P<0.05). Patellar height and patella-femoral angle of high patella group were significantly positively correlated with K-L grades at the level of 0.01 (P<0.05);patella height and patella-femoral angle were not correlated with K-L grades in median patella group(P>0.05). There was no correlation between height of patella and K-L grade in low patella group (P>0.05). There was significant negative correlation between patella-femoral angle and K-L grade at level of 0.05 (P<0.05). CONCLUSION: Inferior femoral angle, tibiofemoral angle, joint gap angle, hip-knee-ankle angle, femoral neck shaft angle and high patella are related to K-L classification of varus KOA, which could be used for early diagnosis and provide objective data for efficacy analysis of conservative treatment.

A Simple Disk Stacking Plus Micro-Elution Method for Rapid Detection of the Synergistic Effect of Aztreonam and Ceftazidime/Avibactam Against Metallo-ß-Lactamase Producing Enterobacterales.

Purpose: To establish and evaluate a simple disk stacking plus micro-elution (DSE) method that can be routinely performed to rapidly detect the synergistic effect between aztreonam (ATM) and ceftazidime/avibactam (CZA) against metallo-ß-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE). Methods: The DSE method was established, and a total of 32 MBL-producing CRE isolates collected from multiple centers were tested for ATM-CZA synergy. The results obtained after 8 h of incubation were compared with those obtained by a reference checkerboard assay (CBA) after 18~24 h. Reproducibility experiments were completed on three separate days. Results: The reproducibility study showed that the results of the DSE method were precise. Compared with CBA, the DSE method exhibited excellent performance, with 92.8% sensitivity, 100.0% specificity 93.8% categorical agreement, 0.0% very major error, 0.0% major error, and 6.2% minor error over three days of testing. Conclusion: The DSE method is a simple, rapid and practical method for ATM-CZA combination testing. Further evaluation should be completed to improve its clinical application.

Polyphosphate kinase 1 is involved in formation, the morphology and ultramicrostructure of biofilm of Mycobacterium smegmatis and its survivability in macrophage.

The most unique characteristic of Mycobacterium tuberculosis is persistence in the human host, and the biofilm formation is related to the persistance. Polyphosphate (polyP) kinase 1 (PPK1) is conserved in Mycobacteria and is responsible for polyP synthesis. polyP is a chain molecule linked by high-energy phosphate bonds, which is considered to play a very important role in bacterial persistence. However, the relationship of PPK1 and mycobacterial biofilm formation is still adequately unclear. In current study, ppk1-deficient mutant (MT), ppk1-complemented (CT) and wild-type strains of M. smegmatis mc2 155 were used to investigate the formation, morphology and ultramicrostructure of the biofilm and to analyze the lipid levels and susceptibility to vancomycin antibiotic. And then WT, MT and CT strains were used to infect macrophages and to analyze the expression levels of various inflammatory factors, respectively. We found that PPK1 was required for M. smegmatis polyP production in vivo and polyP deficiency not only attenuated the biofilm formation, but also altered the phenotype and ultramicrostructure of the biofilm and reduced the cell lipid composition (except for C16.1 and C17.1, most of the fatty acid components from C8-C24). Moreover, the ppk1-deficient mutant was also significantly more sensitive to vancomycin which targets the cell wall, and its ability to survive in macrophages was decreased, which was related to the change of the expression level of inflammatory factors in macrophage. This study demonstrates that the PPK1 can affect the biofilm structure through affecting the content of short chain fatty acid and promote intracellular survival of M. smegmatis by altering the expression of inflammatory factors. These findings establish a basis for investigating the role of PPK1 in the persistence of M. tuberculosis, and provide clues for treating latent infection of M. tuberculosis with PPK1 as a potential drug target.

Indoline CD4-mimetic compounds mediate potent and broad HIV-1 inhibition and sensitization to antibody-dependent cellular cytotoxicity.

Binding to the host cell receptors, CD4 and CCR5/CXCR4, triggers large-scale conformational changes in the HIV-1 envelope glycoprotein (Env) trimer [(gp120/gp41)3] that promote virus entry into the cell. CD4-mimetic compounds (CD4mcs) comprise small organic molecules that bind in the highly conserved CD4-binding site of gp120 and prematurely induce inactivating Env conformational changes, including shedding of gp120 from the Env trimer. By inducing more "open," antibody-susceptible Env conformations, CD4mcs also sensitize HIV-1 virions to neutralization by antibodies and infected cells to antibody-dependent cellular cytotoxicity (ADCC). Here, we report the design, synthesis, and evaluation of novel CD4mcs based on an indoline scaffold. Compared with our current lead indane scaffold CD4mc, BNM-III-170, several indoline CD4mcs exhibit increased potency and breadth against HIV-1 variants from different geographic clades. Viruses that were selected for resistance to the lead indane CD4mc, BNM-III-170, are susceptible to inhibition by the indoline CD4mcs. The indoline CD4mcs also potently sensitize HIV-1-infected cells to ADCC mediated by plasma from HIV-1-infected individuals. Crystal structures indicate that the indoline CD4mcs gain potency compared to the indane CD4mcs through more favorable π-π overlap from the indoline pose and by making favorable contacts with the vestibule of the CD4-binding pocket on gp120. The rational design of indoline CD4mcs thus holds promise for further improvements in antiviral activity, potentially contributing to efforts to treat and prevent HIV-1 infection.

Panax notoginseng saponins promote hair follicle growth in mice via Wnt/ß-Catenin signaling pathway.

Panax notoginseng saponins (PNS), the active ingredients of the traditional Chinese medicine Panax notoginseng, have strong neuroprotective and anti-platelet aggregation effects. To investigate whether PNS can promote hair follicle growth in C57BL/6J mice, the optimal concentration of PNS was initially determined, followed by clarification of the mechanism underlying their effects. Twenty-five male C57BL/6J mice had the hair on a 2 × 3 cm2 area of the dorsal skin shaved and were equally divided into five groups: control group, 5% minoxidil (MXD) group, and three PNS treatment groups [2% (10 mg/kg), 4% (20 mg/kg), and 8% (40 mg/kg) PNS]. They were then intragastrically administered the corresponding drugs for 28 days. The effects of PNS on C57BL/6J mice were analyzed by subjecting their dorsal depilated skin samples to different assessments, including hematoxylin and eosin staining, immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting (WB). The group with 8% PNS exhibited the largest number of hair follicles from 14 days onwards. Compared with the control group, the number of hair follicles increased significantly in the mice treated with 8% PNS and 5% MXD, which significantly increased in a PNS-dose-dependent manner. Immunohistochemistry and immunofluorescence results revealed that treatment with 8% PNS activated the metabolism of hair follicle cells, with them showing higher rates of proliferation and apoptosis than those in the normal group. In qRT-PCR and WB analysis, the expression of ß-catenin, Wnt10b, and LEF1 was upregulated in the PNS and MDX groups compared with that in the control group. Examination of the WB bands revealed that the greatest inhibitory effect of Wnt5a occurred in mice in the 8% PNS group. PNS may promote the growth of hair follicles in mice, with 8% PNS demonstrating the strongest effect. The mechanism behind this may be related to the Wnt/ß-catenin signaling pathway.

Structural and Functional Characterization of Indane-Core CD4-Mimetic Compounds Substituted with Heterocyclic Amines.

The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer on the virion surface interacts with the host receptors, CD4 and CCR5/CXCR4, to mediate virus entry into the target cell. CD4-mimetic compounds (CD4mcs) bind the gp120 Env, block CD4 binding, and inactivate Env. Previous studies suggested that a C(5)-methylamino methyl moiety on a lead CD4mc, BNM-III-170, contributed to its antiviral potency. By replacing the C(5) chain with differentially substituted pyrrolidine, piperidine, and piperazine ring systems, guided by structural and computational analyses, we found that the 5-position of BNM-III-170 is remarkably tolerant of a variety of ring sizes and substitutions, both in regard to antiviral activity and sensitization to humoral responses. Crystallographic analyses of representative analogues from the pyrrolidine series revealed the potential for 5-substituents to hydrogen bond with gp120 Env residue Thr 283. Further optimization of these interactions holds promise for the development of CD4mcs with greater potency.