Does an incomplete ferrule affect the fracture of endodontically treated teeth? A systematic review of in vitro studies.

OBJECTIVE: The purpose of this systematic review was to assess the impact of the incomplete ferrule on the fracture of endodontically treated teeth (ETT). DATA: The keywords such as "incomplete ferrule," "ferrule," "ferrule effect," "residual dentin," "remaining dentin," or "remaining coronal dentin" were used for searching, and only in vitro studies investigating the incomplete ferrule effect on natural teeth were included. SOURCES: PubMed, Medline, Embase, Cochrane Library, and Science Direct databases, and manual-searching. STUDY SELECTION: The search strategy yielded 1633 hits, and a total of 19 in vitro studies closely related to the effect of incomplete ferrule on ETT were included. CONCLUSION: The presence of an incomplete ferrule may significantly increase the fracture resistance of restored ETT, compared with restored ETT without ferrule. The number of residual axial walls of the incomplete ferrule may have an impact on the fracture resistance and fracture mode. The location of residual axial walls of the incomplete ferrule may affect the fracture resistance but not the fracture mode. CLINICAL IMPLICATIONS: Limited data suggest that the presence of incomplete ferrule has a positive effect on the fracture resistance of restored ETT. An incomplete ferrule can be an alternative for restoring ETT when a complete ferrule is not present. Nevertheless, further high-quality studies are still needed to offer more robust evidence and to take potential confounding factors into account.

Network meta-analysis of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults.

OBJECTIVE: To compare the outcomes associated with the use of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults. METHODS: We searched eight electronic databases from database inception to July 11, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the treatment of chronic constipation. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of the evidence was assessed using the Confidence in Network Meta-Analysis framework. The analysis was conducted using R version 4.3.0. RESULTS: Out of the 37 RCTs, a total of 21 different types of interventions were reported, involving 3,903 patients. This NMA demonstrated that both prebiotics and synbiotics resulted in an increase in frequency of stool movements per week. Compared to placebo, lactulose (Mean difference [MD] = 3.39, 95% Confdence interval [CI] [1.13, 5.65], moderate certainty), mix2 (consisting of Lactulose and Bacillus coagulans) (MD = 3.63, 95% CI [1.37, 5.89], moderate certainty), mix6 (consisting of Lactulose and Bifidobacterium coagulans) (MD = 4.30, 95% CI [1.04, 7.54], low certainty), and mix7 (consisting of Lactulose, Bifidobacterium subtilis, and Enterococcus faecium) (MD = 4.58, 95% CI [1.35, 7.78], moderate certainty) exhibited a significant effect. Notably, mix7 demonstrated the highest probability of being the most effective intervention (94.8%). Furthermore, when compared to L. plantarum, four probiotics and two synbiotics showed significant advantages in the Patient Assessment of Constipation Symptoms (PAC-SYM) score. L. reuteri (MD = -13.74, 95% CI [-22.20, -4.66], very low certainty) exhibited a significant effect in improving the Patient Assessment of Constipation Quality of Life (PAC-QoL) score. In terms of safety, there were no statistically significant differences between the intervention and control groups in all adverse event analyses. CONCLUSIONS: Moderate to very low evidence supports the use of lactulose and synbiotics to increase the number of weekly stool movements in patients, particularly highlighting the significant impact of synbiotics in increasing the number of weekly stool movements in patients with constipation. The use of L. paracasei showed improvements in PAC-SYM scores, while L. reuteri demonstrated enhancements in PAC-QoL scores.

No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study.

Objective: We applied Mendelian randomization to explore the causal relationship between obesity and benign paroxysmal vertigo (BPV). Methods: We chose two types of obesity diseases. Obesity due to excessive calories and other or unspecified obesity from the FinnGen database. We used genomic significance (p < 5 × 10-8) to obtain independent single nucleotide polymorphisms (SNPs) as instrumental variables. Similarly, genome-wide association study data for the disease BPV were selected from the FinnGen database. R was then used to test the data for multiplicity and heterogeneity, as well as to detect the effect of individual SNPs on the results. Random effects inverse variance weighting was used as the main statistical analysis. Results: First, by analyzing, we found an outlier in obesity due to excessive calories (rs12956821). Outliers were then removed, and the statistical results were analyzed without heterogeneity (p > 0.05) and horizontal pleiotropy (p > 0.05), as well as individual SNPs having no effect on the results. Meanwhile, random-effects IVW results showed obesity due to excessive calories (p = 0.481; OR = 0.941), and other or unspecified obesity (p = 0.640; OR = 0.964). Conclusions: The present study did not find a causal relationship between the above two obesity types and BPV at the genetic level.

A WeChat-based nursing intervention program improves the postoperative rehabilitation of breast cancer patients: results from a randomized controlled trial.

Background: In postoperative setting, breast cancer (BC) patients can experience adverse effects, including fatigue, sleep disorders, and pain, which substantially affect their health-related quality of life (HRQoL). This study sought to assess the effectiveness of a WeChat-based multimodal nursing program (WCBMNP) that was specifically designed for the rehabilitation of women following BC surgery. Methods: BC patients were randomly, single-blinded allocated to either the intervention (n=62) or control (n=63) cohorts. Over a period of 6 months (24 weeks), the intervention cohort received a WCBMNP in addition to routine nursing care, while the control cohort received routine nursing care only. To evaluate patients' fear of cancer recurrence (FCR), their overall fear score was assessed using the Japanese version of the Concerns About Recurrence Scale (CARS-J) for primary outcome. The initial outcome (HRQoL) and secondary results, such as fatigue, sleep, and pain, were examined using the Functional Assessment of Cancer Therapy-Breast (FACT-B, version 4.0) and Nursing Rating Scale (NRS), respectively. Results: Two hundred and ten participants, 85 participants were excluded. Compared to the controls (n=63), the intervention cohort (n=62) showed statistically significant improvements in their CARS-J scores. The intervention cohort aggregate scores on the FACT-B improved significantly but were affected by the compounding influences of cohort dynamics, temporal progression, and their interaction. Similar improvements were observed in the social/family and functional well-being domains. Emotional well-being was improved based on the effects of time and group-time interaction. In the intervention cohort, the "BC-specific subscale for additional concerns" was affected by group and time, whereas physical well-being was only affected by time. Conversely, there were no statistically significant changes in the variables of fatigue, sleep, and pain. Conclusions: The WCBMNP reduced FCR and significantly increased the HRQoL of female patients with BC postoperatively. The WCBMNP could be implemented as a postoperative rehabilitation intervention in this patient population to improve outcomes. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2400081557).

Combining a CAD-CAM composite resin palatal wall with a direct composite resin layering technique for the restoration of a large Class IV fracture: A clinical report.

This clinical report presents combining a computer-aided design and computer-aided manufacturing (CAD-CAM) composite resin palatal wall with a direct composite resin layering technique for the esthetic and functional restoration of a large Class IV fracture of a maxillary central incisor to achieve optimal esthetic and functional outcomes.

Network Pharmacology Analysis of Liquid-Cultured Armillaria ostoyae Mycelial Metabolites and Their Molecular Mechanism of Action against Gastric Cancer.

Armillaria sp. are traditional edible medicinal mushrooms with various health functions; however, the relationship between their composition and efficacy has not yet been determined. Here, the ethanol extract of liquid-cultured Armillaria ostoyae mycelia (AOME), a pure wild Armillaria sp. strain, was analyzed using UHPLC-QTOF/MS, network pharmacology, and molecular docking techniques. The obtained extract affects various metabolic pathways, such as JAK/STAT and PI3K/AKT. The extract also contains important compounds such as 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl] benzamide, isoliquiritigenin, and 7-hydroxycoumarin. Moreover, the extract targets key proteins, including EGFR, SCR, and IL6, to suppress the progression of gastric cancer, thereby synergistically inhibiting cancer development. The molecular docking analyses indicated that the main compounds stably bind to the target proteins. The final cell culture experimental data showed that the ethanol extract inhibited MGC-803 gastric cancer cells. In summary, our research revealed the beneficial components of AOME for treating gastric cancer and its associated molecular pathways. However, further research is needed to confirm its effectiveness and safety in gastric cancer patients.

Chemical characterisation of essential oil from Sambucus williamsii Hance leaves and its hepatoprotective effects.

This study is the first to examine the effect of leaves of Sambucus williamsii Hance essential oil on acute liver injury. According to gas chromatography-mass spectrometry analysis, the major constituents of S. williamsii essential oil (SEO)were (S)-falcarinol (62.66%), 17-pentatriacontene (7.78%) and tetrapentacontane (8.64%). Mice were pre-treated with SEO for 6 days followed by inducing liver injury with CCl4. The results indicated that SEO protected the liver against CCl4-induced injuries. Elevated levels of alanine-aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP) in serum were significantly reduced on SEO pre-treatment. SEO pre-treatment significantly inhibited the oxidative stress and inflammation. Furthermore, toll-like receptor-4 (TLR4)/nuclear factor kappa-B (NF-κB) signalling pathways were significantly modulated by SEO in the liver tissue. The findings demonstrate that the essential oil of S. williamsii has enhancing the resistance to CCl4-induced liver injury.

Application of PRI-E-a combined learning method in oral and maxillofacial oncology education.

The traditional lecture-based learning (LBL) method is facing great challenges due to its low efficiency and single proceeding form. We designed a PRI-E learning mode that combined and modified problem-based, case-based, and evidence-based learning with a step-by-step approach. We evaluated the practical learning outcomes of using the PRI-E mode by comparing it with traditional lecture-based learning in oral and maxillofacial oncology education. "PRI-E" consists of the first letters of the English words Passion, Research, Innovation, and Education, and it means "the best Education". This prospective randomized controlled trial included 40 participants. We evenly divided the participants into the PRI-E (n = 20) and LBL group (n = 20) based on the entrance test scores. The same staff group designed and then taught the learning content with different group measures. The evaluation included the final test scores and questionnaire assessments. Without affecting the examination results, the PRI-E teaching method was more satisfactory and popular with participants in terms of ability development and classroom participation. Enacting the PRI-E teaching method required more time, but this did not affect its popularity among the participants. Compared with the LBL learning mode, the PRI-E learning mode was more organized and efficient in oral and maxillofacial oncology education without affecting academic performance. This model has a high degree of satisfaction, which is conducive to training students' comprehensive ability.

Multifaceted Characterization for the Hepatic Clearance of Graphene Oxide and Size-Related Hepatic Toxicity.

Understanding the final fate of nanomaterials (NMs) in the liver is crucial for their safer application. As a representative two-dimensional (2D) soft nanomaterial, graphene oxide (GO) has shown to have high potential for applications in the biomedical field, including in biosensing, drug delivery, tissue engineering, therapeutics, etc. GO has been shown to accumulate in the liver after entering the body, and thus, understanding the GO-liver interaction will facilitate the development of safer bio-applications. In this study, the hepatic clearance of two types of PEGylated GOs with different lateral sizes (s-GOs: ~70 nm and l-GOs: ~300 nm) was carefully investigated. We found that GO sheets across the hepatic sinusoidal endothelium, which then may be taken up by the hepatocytes via the Disse space. The hepatocytes may degrade GO into dot-like particles, which may be excreted via the hepatobiliary route. In combination with ICP-MS, LA-ICP-MS, and synchrotron radiation FTIR techniques, we found that more s-GO sheets in the liver were prone to be cleared via hepatobiliary excretion than l-GO sheets. A Raman imaging analysis of ID/IG ratios further indicated that both s-GO and l-GO generated more defects in the liver. The liver microsomes may contribute to GO biotransformation into O-containing functional groups, which plays an important role in GO degradation and excretion. In particular, more small-sized GO sheets in the liver were more likely to be cleared via hepatobiliary excretion than l-GO sheets, and a greater clearance of s-GO will mitigate their hepatotoxicity. These results provide a better understanding of the hepatic clearance of soft NMs, which is important in the safer-by-design of GO.

BNST GABAergic neurons modulate wakefulness over sleep and anesthesia.

The neural circuits underlying sleep-wakefulness and general anesthesia have not been fully investigated. The GABAergic neurons in the bed nucleus of the stria terminalis (BNST) play a critical role in stress and fear that relied on heightened arousal. Nevertheless, it remains unclear whether BNST GABAergic neurons are involved in the regulation of sleep-wakefulness and anesthesia. Here, using in vivo fiber photometry combined with electroencephalography, electromyography, and video recordings, we found that BNST GABAergic neurons exhibited arousal-state-dependent alterations, with high activities in both wakefulness and rapid-eye movement sleep, but suppressed during anesthesia. Optogenetic activation of these neurons could initiate and maintain wakefulness, and even induce arousal from anesthesia. However, chronic lesion of BNST GABAergic neurons altered spontaneous sleep-wakefulness architecture during the dark phase, but not induction and emergence from anesthesia. Furthermore, we also discovered that the BNST-ventral tegmental area pathway might participate in promoting wakefulness and reanimation from steady-state anesthesia. Collectively, our study explores new elements in neural circuit mechanisms underlying sleep-wakefulness and anesthesia, which may contribute to a more comprehensive understanding of consciousness and the development of innovative anesthetics.

Effect of ceramic type and thickness on the masking ability of chairside machinable all-ceramic crowns.

OBJECTIVES: This study aimed to evaluate the influence of ceramic type and thickness on the masking ability and final aesthetic effects of chairside machinable all-ceramic crowns. METHODS: Six kinds from three types chairside machinable ceramic materials (IPS e.max CAD HT/MT/LT, IPS Empress LT, and VITA Suprinity HT/T) in shade A2 were fabricated to slice specimens into 1.0, 1.5, and 2.0 mm-thick sections (n=10). The color parameters of the specimens against black and white tiles and four resin substrates (A2, A4, B3, and C4 shade) were measured with a spectrophotometer. The translucency parameter (TP) was calculated using color parameters measured over standard white and black backgrounds. The color differences (ΔE) were calculated between there substrate shades (A4, B3, C4 ) and A2 shade (control group). Two-way analysis of variance (ANOVA) was performed on the TP values. The two va-riables were ceramic type and ceramic thickness. Three-way ANOVA was used to determine the effects of ceramic materials, ceramic thickness, and substrate shades on the ΔE values, followed by Tukey test for multiple comparisons (α=0.05). RESULTS: Ceramic type, ceramic thickness, and substrate shade significantly affected the ΔE values (P<0.001). The L* and b* values of the specimens increased with increasing ceramic thickness, except in substrate A2, whereas the ΔE values decreased. The color difference of all 1.0 mm-thick specimens or all specimens over the substrates C4 shade exceeded the clinically acceptable threshold (ΔE>3.3). CONCLUSIONS: The masking ability of chairside machinable all-ceramic crowns is influenced by ceramic type and thickness, and ceramic material. The thickness of ceramic less than 2.0 mm cannot mask the gray shade abutment.

THE ACCURACY OF INTRAORAL SCAN IN OBTAINING DIGITAL IMPRESSIONS OF EDENTULOUS ARCHES: A SYSTEMATIC REVIEW.

OBJECTIVES: Accuracy is a crucial factor when assessing the quality of digital impressions. This systematic review aims to assess the accuracy of intraoral scan (IOS) in obtaining digital impressions of edentulous jaws. METHODS: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was registered in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42022382983). A thorough retrieval of 7 electronic databases was undertaken, encompassing MEDLINE (PubMed), Web of Science, EMBASE, Scopus, Cochrane Library, Virtual Health Library, and Open gray, through September 11, 2023. A snowball search was performed by tracing the reference lists of the included studies. The Population, Intervention, Comparison, and Outcome (PICO) question of this systematic review was: "What is the accuracy of intraoral scan in obtaining digital impressions of edentulous arches?" The Modified Methodological Index for Nonrandomized Studies (MINORS) was employed to assess the risk of bias. RESULTS: Among the studies retrieved from databases and manual search, a total of 25 studies were selected for inclusion in this systematic review, including 9 in vivo and 16 in vitro studies. Twenty-one of the included studies utilized the 3D deviation analysis method, while 4 studies employed the linear or angular deviation analysis method. The accuracy results of in vitro studies indicated a trueness range of 20-600 µm and a precision range of 2-700 µm. Results of in vivo studies indicated a trueness range of 40-1380 µm, while the precision results were not reported. CONCLUSION: According to the results of this study, direct digital impressions by IOS cannot replace the conventional impressions of completely edentulous arches in vivo. Edentulous digital impressions by IOS demonstrated poor accuracy in peripheral areas with mobile tissues, such as the soft palate, vestibular sulcus, and sublingual area.

Circular RNA circVmn2r1 acts as a miR-223-3p sponge to promote kidney aging by regulating NLRP3 expression in mice.

Kidney aging accelerates the progression of various acute and chronic kidney diseases and can also induce pathological changes in other organs throughout the body. Circular RNAs (circRNAs), have been demonstrated to play a vital role in aging and age-related diseases. However, biological functions and the underlying molecular mechanism of circRNAs in kidney aging remain largely unclear. Uncovering the functions of circRNAs in kidney aging and their underlying regulatory mechanisms may shed new light on the development of novel diagnostic and therapeutic strategies for human aging. Here we report the important role of circVmn2r1 in the progression of kidney aging. We found that circVmn2r1 was one of the top expressed circRNAs in mouse kidney by RNA sequencing and was significantly upregulated in 24-month-old mouse kidney compared to 3-month-old. More importantly, we demonstrated that overexpression of circVmn2r1 promoted kidney aging in senescence-accelerated mouse prone 8 (SAMP8) mice. Cellular assays with mouse kidney tubular epithelium (TCMK-1) cells under both gain-of-function and loss-of-function conditions demonstrated that circVmn2r1 inhibited proliferation and promoted senescence, whereas miR-223-3p counteracted these effects. Mechanistic analysis demonstrated that circVmn2r1 acted as a miR-223-3p sponge to relieve the repressive effect of miR-223-3p on its target NLRP3, which we proved could inhibit proliferation and promote senescence of TCMK-1 cells. Our results indicate that circVmn2r1 promotes kidney aging through acting as a miR-223-3p sponge, consequently upregulating NLRP3 expression, and can be a valuable diagnostic marker and an important therapeutic target for kidney aging.

Eimeria tenella pyrroline -5-carboxylate reductase is a secreted protein and involved in host cell invasion.

Chicken coccidiosis, which caused by Eimeria spp, is a parasitic protozoal disease. At present, control measures of this disease depend mainly on anticoccidial drugs and live vaccines. But these control strategies have drawbacks such as drug resistance and limitations in live vaccines production. Therefore, novel control approaches are urgently need to study to control this disease effectively. In this study, the function and characteristics of the pyrroline-5-carboxylate reductase of Eimeria tenella (EtPYCR) protein were preliminary analyzed. The transcription and translation level were analyzed by using qPCR and Western blot. The results showed that the mRNA transcription and translation levels of EtPYCR were higher in unsporulated oocysts (UO) and second generation merozoites (Mrz) than that in sporulated oocysts (SO) and sporozoites. Enzyme activity showed that the enzyme activity of EtPYCR was also higher in the UO and Mrz than that in the SO and sporozoites. Immunofluorescence localization showed EtPYCR was mainly located on the top of sporozoites and the whole cytoplasm and surface of Mrz. The secretion assay indicated that EtPYCR was secretion protein, but not from micronemes. Invasion inhibition assay showed that rabbit anti-rEtPYCR polyclonal antibodies can effectively inhibit sporozoite invasion of DF-1 cells. These results showed that EtPYCR possess several important roles that separate and distinct from its conversion 1-pyrroline-5-carboxylate (P5C) into proline and maybe involved in the host cell invasion and development of parasites in host cells.

OsNAC103, a NAC Transcription Factor, Positively Regulates Leaf Senescence and Plant Architecture in Rice.

Leaf senescence, the last stage of leaf development, is essential for crop yield by promoting nutrition relocation from senescence leaves to new leaves and seeds. NAC (NAM/ATAF1/ATAF2/CUC2) proteins, one of the plant-specific transcription factors, widely distribute in plants and play important roles in plant growth and development. Here, we identified a new NAC member OsNAC103 and found that it plays critical roles in leaf senescence and plant architecture in rice. OsNAC103 mRNA levels were dramatically induced by leaf senescence as well as different phytohormones such as ABA, MeJA and ACC and abiotic stresses including dark, drought and high salinity. OsNAC103 acts as a transcription factor with nuclear localization signals at the N terminal and a transcriptional activation signal at the C terminal. Overexpression of OsNAC103 promoted leaf senescence while osnac103 mutants delayed leaf senescence under natural condition and dark-induced condition, meanwhile, senescence-associated genes (SAGs) were up-regulated in OsNAC103 overexpression (OsNAC103-OE) lines, indicating that OsNAC103 positively regulates leaf senescence in rice. Moreover, OsNAC103-OE lines exhibited loose plant architecture with larger tiller angles while tiller angles of osnac103 mutants decreased during the vegetative and reproductive growth stages due to the response of shoot gravitropism, suggesting that OsNAC103 can regulate the plant architecture in rice. Taken together, our results reveal that OsNAC103 plays crucial roles in the regulation of leaf senescence and plant architecture in rice.

Comparison of effectiveness and safety of lasmiditan and CGRP-antagonists for the acute treatment of migraine in adults: systematic review and network meta-analysis of randomised trials.

OBJECTIVE: To compare the outcomes associated with the use of lasmiditan, rimegepant, ubrogepant, and zavegepant for the acute management of migraine headaches. METHODS: We searched four electronic databases from database inception to August 31, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the acute treatment of migraine. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of evidence using the CINeMA approach. We conducted frequentist network meta-analyses (NMA) to summarise the evidence. Data were analyzed using R-4.3.1. RESULTS: A total of 18 eligible studies including 10 different types of interventions with 22,429 migraine patients were included. NMA results showed that compared to ubrogepant (25 mg and 50 mg) and zavegepant, lasmiditan (100 mg and 200 mg) exhibits an elevated probability of achieving pain relief within a 2-hour interval. Similarly, relative to zavegepant, rimegepant (75 mg) and ubrogepant (50 mg and 100 mg) demonstrate an enhanced likelihood of sustaining pain relief over a 24-hour period. Furthermore, in contrast to ubrogepant (25 mg) and lasmiditan (50 mg), rimegepant (75 mg) presents a heightened probability of achieving freedom from photophobia within 2 h. Regarding safety, lasmiditan carries the highest risk of adverse events, which are associated with an increased incidence of adverse effects, including dizziness, somnolence, asthenia, paresthesia, and fatigue. CONCLUSIONS: In this NMA, a spectrum of evidence ranging from very low to high levels underscores the favorable efficacy and tolerability of rimegepant 75 mg and ubrogepant 100 mg, positioning them as potential candidates for the acute management of migraine. Concurrently, lasmiditan (100 mg and 200 mg) exhibits notable efficacy, albeit accompanied by an increased susceptibility to adverse events. These findings should still be approached with caution, primarily due to the intrinsic limitations associated with indirect comparisons.

Portulaca oleracea L. extract relieve mice liver fibrosis by inhibiting TLR-4/NF-κB, Bcl-2/Bax and TGF-ß1/Smad2 signalling transduction.

Portulaca oleracea L. are annual herb, which has various pharmacological effects including hepatoprotective property. However, the effect of Portulaca oleracea L. (POL-1) in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and its mechanism of action have not been clarified. POL-1 ameliorated the CCl4-induced liver fibrosis in mice, as shown by decreased collagen deposition and the decreased expression of liver fibrosis marker collagen I and α-smooth muscle actin (α-SMA) mRNA. In addition, treatment with POL-1 suppressed the proliferation of activated human hepatic stellate cell line (LX-2). POL-1 inhibited the oxidative stress and inflammation in fibrotic livers of mice. Mechanistically, POL-1 inhibited the CCl4-induced expression of toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa-B (NF-κBp65) p65, Bcl2-associated X (Bax), transforming growth factor-ß1 (TGF-ß1) and drosophila mothers against decapentaplegic 2 (Smad2) proteins, upregulated B-cell lymphoma -2 (Bcl-2) proteins in livers of mice. These findings suggested that POL-1 attenuated liver fibrosis.

Comparative efficacy of exercise modalities on sleep quality in populations with sleep disorders: A systematic review and network meta-analysis.

The effect of various exercise modalities on people with sleep disorders remains unclear. This network meta-analysis aims to explore the effects of various exercise modalities in improving sleep quality in people with sleep disorders. Four electronic databases were searched from inception to April 8, 2023. We conducted pairwise meta-analyses and frequentist network meta-analyses with random effects models. A total of 17 randomized controlled trials enrolled 1090 participants were included. Compared with passive control, with moderate-to-low certainty of evidence, mind-body exercise combined with treatment as usual [standard mean difference (SMD) = -2.26, 95% confidence interval (CI) (-3.29, -1,24)], moderate aerobic exercise combined with light strength exercise [SMD = -1.26, 95% CI (-2.22, -0.31)], mind-body exercise [SMD = -0.81, 95% CI (-1.37, -0.25)] and moderate aerobic exercise [SMD = -0.75, 95% CI (-1.38, -0.13)] were more effect in improving sleep disorders. Various exercise modalities have favorable effects on sleep quality for people with sleep disorders compared with passive control. However, due to the low quality of evidence, well-designed trials should be conducted to elucidate these promising findings in the future.

Holistic bursting cells store long-term memory in auditory cortex.

The sensory neocortex has been suggested to be a substrate for long-term memory storage, yet which exact single cells could be specific candidates underlying such long-term memory storage remained neither known nor visible for over a century. Here, using a combination of day-by-day two-photon Ca2+ imaging and targeted single-cell loose-patch recording in an auditory associative learning paradigm with composite sounds in male mice, we reveal sparsely distributed neurons in layer 2/3 of auditory cortex emerged step-wise from quiescence into bursting mode, which then invariably expressed holistic information of the learned composite sounds, referred to as holistic bursting (HB) cells. Notably, it was not shuffled populations but the same sparse HB cells that embodied the behavioral relevance of the learned composite sounds, pinpointing HB cells as physiologically-defined single-cell candidates of an engram underlying long-term memory storage in auditory cortex.

Insights into the selectivity of a brain-penetrant CDK4/6 vs CDK1/2 inhibitor for glioblastoma used in multiple replica molecular dynamics simulations.

Cyclin dependent kinases (CDKs) play an important role in cell cycle regulation and their dysfunction is associated with many cancers. That is why CDKs have been attractive targets for the treatment of cancer. Glioblastoma is a cancer caused by the aberrant expression of CDK4/6, so exploring the mechanism of the selection of CDK4/6 toward inhibitors relative to the other family members CDK1/2 is essential. In this work, multiple replica molecular dynamics (MRMD) simulations, principal component analysis (PCA), free energy landscapes (FELs), molecular mechanics Poisson-Boltzmann/Generalized Born surface area (MM-PB/GBSA) and other methods were integrated to decipher the selectively binding mechanism of the inhibitor N1J to CDK4/6 and CDK1/2. Molecular electrostatic potential (MESP) analysis provides an explanation for the N1J selectivity. Residue-based free energy decomposition reveals that most of the hot residues are located at the same location of CDKs proteins, but the different types of residues in different proteins cause changes in binding energy, which is considered as a potential developmental direction to improve the selectivity of inhibitors to CDK4/6. These results provide insights into the source of inhibitor and CDK4/6 selectivity for the future development of more selective inhibitors.Communicated by Ramaswamy H. Sarma.