An ON-type direction-selective ganglion cell in primate retina.

To maintain a stable and clear image of the world, our eyes reflexively follow the direction in which a visual scene is moving. Such gaze-stabilization mechanisms reduce image blur as we move in the environment. In non-primate mammals, this behaviour is initiated by retinal output neurons called ON-type direction-selective ganglion cells (ON-DSGCs), which detect the direction of image motion and transmit signals to brainstem nuclei that drive compensatory eye movements1. However, ON-DSGCs have not yet been identified in the retina of primates, raising the possibility that this reflex is mediated by cortical visual areas. Here we mined single-cell RNA transcriptomic data from primate retina to identify a candidate ON-DSGC. We then combined two-photon calcium imaging, molecular identification and morphological analysis to reveal a population of ON-DSGCs in the macaque retina. The morphology, molecular signature and GABA (γ-aminobutyric acid)-dependent mechanisms that underlie direction selectivity in primate ON-DSGCs are highly conserved with those in other mammals. We further identify a candidate ON-DSGC in human retina. The presence of ON-DSGCs in primates highlights the need to examine the contribution of subcortical retinal mechanisms to normal and aberrant gaze stabilization in the developing and mature visual system.

Passive endocytosis in model protocells.

Semipermeable membranes are a key feature of all living organisms. While specialized membrane transporters in cells can import otherwise impermeable nutrients, the earliest cells would have lacked a mechanism to import nutrients rapidly under nutrient-rich circumstances. Using both experiments and simulations, we find that a process akin to passive endocytosis can be recreated in model primitive cells. Molecules that are too impermeable to be absorbed can be taken up in a matter of seconds in an endocytic vesicle. The internalized cargo can then be slowly released over hours, into the main lumen or putative cytoplasm. This work demonstrates a way by which primitive life could have broken the symmetry of passive permeation prior to the evolution of protein transporters.

Predictive Factors for Successful Same-Day Discharge After Minimally Invasive Colectomy and Stoma Reversal.

BACKGROUND: Same-day discharge after minimally invasive colorectal surgery is a safe, effective practice in specific patients that can enhance the efficiency of enhanced recovery pathways. OBJECTIVE: To identify predictive factors associated with success or failure of same-day discharge. DESIGN: Prospective cohort study from January 2020 to March 2023. SETTINGS: Tertiary colorectal center. PATIENTS: Adult patients eligible for same-day discharge with remote postdischarge follow-up included those with minimal comorbidities, residing near the hospital, having sufficient home support, and owning a mobile device. INTERVENTIONS: Patients were discharged on the day of surgery upon meeting specific criteria, including adequate pain control, tolerance of oral intake, independent mobility, urination, and the absence of complications. Successful same-day discharge was defined as discharge on the day of surgery without unplanned visits in the first 72 hours. MAIN OUTCOME MEASURES: Factors associated with successful or failed same-day discharge after minimally invasive colorectal surgery. RESULTS: A total of 175 patients (85.3%) were discharged on the day of surgery, with 14 patients (8%) having an unplanned visit within 72 hours. Overall, 161 patients (78.5%) were categorized as same-day discharge success and 44 patients (21.5%) as same-day discharge failure. The same-day discharge failure group had a higher Charlson Comorbidity Index (3.7 vs 2.8, p = 0.03). Mean length of stay (0.8 vs 3.0, p = 0.00), 30-day complications (10% vs 48%, p = 0.00), and readmissions (8% vs 27%, p = 0.00) were higher in the same-day discharge failure group. Regression analysis showed that failed same-day discharge was associated with higher comorbidities (OR 0.79; 95% CI, 0.66-0.95) and prolonged postanesthesia care unit time (OR 0.99; 95% CI, 0.99-0.99). Individuals who received a regional nerve block (OR 4.1; 95% CI, 1.2-14) and those who did not consume postoperative opioids (OR 4.6; 95% CI, 1-21) were more likely to have successful same-day discharge. LIMITATIONS: Single-center study. CONCLUSIONS: Our findings indicate that comorbidities and prolonged postanesthesia care unit stays were associated with same-day discharge failure, whereas regional nerve blocks and minimal postoperative opioids were related to success. These factors may inform future research aiming to enhance colorectal surgery recovery protocols. See Video Abstract . FACTORES PREDICTIVOS PARA UN ALTA EXITOSA EL MISMO DA DESPUS DE UNA COLECTOMA MNIMAMENTE INVASIVA Y REVERSIN DEL ESTOMA: ANTECEDENTES:El alta el mismo día después de una cirugía colorrectal mínimamente invasiva es una práctica segura y eficaz en pacientes específicos que puede mejorar la eficiencia de las vías de recuperación mejoradas.OBJETIVO:Identificar factores predictivos asociados con el éxito o fracaso del alta el mismo día.DISEÑO:Estudio de cohorte prospectivo del 01/2020 al 03/2023.AJUSTES:Centro colorrectal terciario.PACIENTES:Los pacientes adultos elegibles para el alta el mismo día con seguimiento remoto posterior al alta incluyeron aquellos con comorbilidades mínimas, que residían cerca del hospital, tenían suficiente apoyo en el hogar y poseían un dispositivo móvil.INTERVENCIONES:Los pacientes fueron dados de alta el día de la cirugía al cumplir con criterios específicos, incluido un control adecuado del dolor, tolerancia a la ingesta oral, movilidad independiente, micción y ausencia de complicaciones. El alta exitosa el mismo día se definió como el alta el día de la cirugía sin visitas no planificadas en las primeras 72 horas.PRINCIPALES MEDIDAS DE RESULTADO:Factores asociados con el alta exitosa o fallida el mismo día después de una cirugía colorrectal mínimamente invasiva.RESULTADOS:Un total de 175 (85,3%) pacientes fueron dados de alta el día de la cirugía y 14 (8%) pacientes tuvieron una visita no planificada dentro de las 72 horas. En total, 161 (78,5%) pacientes se clasificaron como éxito del alta el mismo día y 44 (21,5%) pacientes como fracaso del alta el mismo día. El grupo de fracaso del alta el mismo día tuvo un índice de comorbilidad de Charlson más alto (3,7, 2,8, p = 0,03). La duración media de la estancia hospitalaria (0,8, 3,0, p = 0,00), las complicaciones a los 30 días (10%, 48%, p = 0,00) y los reingresos (8%, 27%, p = 0,00) fueron mayores en el mismo día grupo de fallo de descarga. El análisis de regresión mostró que el alta fallida el mismo día se asoció con mayores comorbilidades (OR 0,79; IC del 95 %: 0,66; 0,95) y tiempo prolongado en la unidad de cuidados postanestésicos (OR 0,99; IC del 95 %: 0,99; 0,99). Las personas que recibieron un bloqueo nervioso regional (OR 4,1; IC del 95 %: 1,2, 14) y aquellos que no consumieron opioides posoperatorios (OR 4,6, IC del 95 %: 1-21) tuvieron más probabilidades de tener éxito en el mismo día -descarga.LIMITACIONES:Estudio unicéntrico.CONCLUSIONES:Nuestros hallazgos indican que las comorbilidades y las estancias prolongadas en la unidad de cuidados postanestésicos se asociaron con el fracaso del alta el mismo día, mientras que los bloqueos nerviosos regionales y los opioides postoperatorios mínimos se relacionaron con el éxito. Estos factores pueden informar investigaciones futuras destinadas a mejorar los protocolos de recuperación de la cirugía colorrectal. (Traducción-Yesenia Rojas-Khalil ).

Willingness to provide a hair sample for drug testing: results from an anonymous multi-city intercept survey.

Background: Hair provision for drug testing can provide secondary measurement to complement self-reported drug use data, thereby providing a more accurate representation of an individual's drug use. Understanding factors associated with hair provision offers valuable insights into recruitment methods.Objective: To identify demographic and drug-related correlates of providing hair samples in a multi-site venue-intercept study.Methods: We utilized venue-intercept sampling for our Rapid Street Reporting study across 12 US cities between January and November 2022. Participants reported past 12-month drug use and were asked if they would provide a hair sample. We conducted multivariable (generalized linear model with logit link) analyses on demographics and drug use characteristics correlated to hair provision for drug testing.Results: Among 3,045 participants, 55.8% were male, 13.6% provided hair samples. Compared to males, those identifying as "other gender" had higher odds of hair collection (adjusted odds ratio = 2.24, 95% confidence interval: 1.28-3.80). Participants identifying as Black (aOR = 0.32, CI: 0.23-0.45) or "other race" (aOR = 0.50, 95% CI: 0.29-0.80) had lower odds of providing hair than those identifying as White. All levels of reported drug use - one drug (aOR=1.50, 95% CI: 1.15-1.96), two-three drugs (aOR=1.51, 95% CI: 1.11-2.05), four or more (aOR = 2.13, 95% CI: 1.50-3.01) - had higher odds of providing hair samples than those reporting no drug use. Similar associations applied to reporting cannabis use with or without another drug (aOR = 1.52-1.81, 95% CI: 1.15-2.38).Conclusion: Differential hair provision based on participant sex, race/ethnicity, and drug use may introduce biases in drug testing, limiting generalizability to individuals from minority backgrounds.

Endodontic microsurgery and prosthodontic treatment of a permanent anterior concrescence: A case report.

Concrescence is a rare dental anomaly in which two adjacent teeth are united only by their cementum. Concrescence most frequently occurs in molars, especially a third mandibular molar and a supernumerary tooth. It is rarely seen in the maxillary anterior teeth. This case report is the first in the literature which details the successful treatment of a concrescence between the maxillary central incisor and a supernumerary tooth through multidisciplinary therapy. The treatment plan included root canal treatment, endodontic microsurgery, and prosthodontic treatment.

Efficacy of the combination of Chinese herbal medicine and negative pressure wound therapy in the treatment of patients with diabetic foot ulcer: A meta-analysis.

This study aimed to systematically evaluate the clinical efficacy of Chinese herbal medicine combined with negative pressure wound therapy (NPWT) in the treatment of diabetic foot ulcers (DFU). Computerised searches of the China National Knowledge Infrastructure, Wanfang, Chinese BioMedical Literature Database, PubMed, Cochrane Library and Embase databases were conducted for randomised controlled trials on the use of Chinese herbal medicines combined with NPWT for the treatment of DFU. The search period ranged from the time of establishment of each database to July 2023. Literature screening and data extraction were performed independently by two investigators, and the quality of the included studies was assessed. The meta-analysis was performed using Review Manager 5.4 software. A total of 25 studies were analysed, including 1777 DFUs, with 890 and 887 patients in the experimental and control groups, respectively. The results showed that the treatment of DFUs with a Chinese herbal medicine in combination with NPWT increased the overall effectiveness (odds ratio [OR] = 4.32, 95% confidence interval [CI]: 2.96-6.30, p < 0.001), wound healing rate (mean difference [MD] = 18.35, 95% CI: 13.07-23.64, p < 0.001) and ankle brachial index (MD = 0.10, 95% CI: 0.06-0.14, p < 0.001); reduced the wound healing time (MD = -11.01, 95% CI: -13.25 to -8.78, p < 0.001) and post-treatment wound area (MD = -1.73, 95% CI: -2.46 to -1.01, p < 0.001); decreased the C-reactive protein level (MD = -3.57, 95% CI: -5.13 to -2.00, p < 0.001); and increased vascular endothelial growth factor level (MD = 19.20, 95% CI: 8.36-30.05, p < 0.001). Thus, Chinese herbal medicines combined with NPWT can effectively promote wound healing, reduce inflammation and shorten the disease course in patients with DFU, while demonstrating precise clinical efficacy.

Using Holographic Microscopy To Measure the Effect of Confinement on Crowding Agents in Lipid Vesicles.

The hydrodynamic effects of macromolecular crowding inside cells are often studied in vitro by using polymers as crowding agents. Confinement of polymers inside cell-sized droplets has been shown to affect the diffusion of small molecules. Here we develop a method, based on digital holographic microscopy, to measure the diffusion of polystyrene microspheres that are confined within lipid vesicles containing a high concentration of solute. We apply the method to three solutes of varying complexity: sucrose, dextran, and PEG, prepared at ∼7 % (w/w). We find that diffusion inside and outside the vesicles is the same when the solute is sucrose or dextran that is prepared below the critical overlap concentration. For poly(ethylene glycol), which is present at a concentration higher than the critical overlap concentration, the diffusion of microspheres inside vesicles is slower, hinting at the potential effects of confinement on crowding agents.

A retrospective analysis of early discharge following minimally invasive colectomy in an enhanced recovery pathway.

BACKGROUND: There is increasing evidence to support discharge prior to gastrointestinal recovery following colorectal surgery. Furthermore, many patients are discharged early despite being excluded from an ambulatory colectomy pathway. The objective of this study was to determine the outcomes of patients discharged early following laparoscopic colectomy in an enhanced recovery pathway (ERP). METHODS: A retrospective review of all adult patients undergoing elective laparoscopic colectomy at a single university-affiliated colorectal referral center (08/2017-06/2021) was performed. Patients were included if they had undergone elective laparoscopic colectomy or ileostomy closure and excluded if they had been enrolled in an ambulatory colectomy pathway. Patients were then divided into three groups: LOS =1 day, LOS 2-3 days, and LOS 4+ days. The main outcomes were 30-day emergency room (ER) visits and readmissions. Reasons for inpatient stay per post-operative day (POD) were also recorded. RESULTS: A total of 497 patients were included [LOS1 n = 63 (13%), LOS2-3 n = 284 (57%), and LOS4+ n = 150 (30%)]. There were no differences in patient characteristics, diagnosis, or procedure between the groups. Patients were discharged with gastrointestinal recovery (GI-3) in 54% LOS1 vs. 98% LOS2-3 vs. 100% LOS4+ (p<0.001). Shorter procedure duration, transversus abdominus plane block, and lower opioid requirements were associated with shorter LOS (p<0.001). The absence of flatus was the most common reason to keep patients hospitalized: 61% on POD1, 21% on POD2, and 8% on POD3 (p<0.001). There were no differences in 30-day emergency visits, or readmission between the groups. In the LOS1 group, there were no differences in outcomes between patients with full return of bowel function at discharge compared to those without. CONCLUSION: Discharge on POD1 was not associated with increased emergency department use, complications, or readmissions. Importantly, full return of bowel function at discharge did not affect outcomes. There may be potential to expand eligibility criteria for ambulatory colectomy protocol.

RNA polymerase clamp conformational dynamics: long-lived states and modulation by crowding, cations, and nonspecific DNA binding.

The RNA polymerase (RNAP) clamp, a mobile structural element conserved in RNAP from all domains of life, has been proposed to play critical roles at different stages of transcription. In previous work, we demonstrated using single-molecule Förster resonance energy transfer (smFRET) that RNAP clamp interconvert between three short-lived conformational states (lifetimes ∼ 0.3-0.6 s), that the clamp can be locked into any one of these states by small molecules, and that the clamp stays closed during initial transcription and elongation. Here, we extend these studies to obtain a comprehensive understanding of clamp dynamics under conditions RNAP may encounter in living cells. We find that the RNAP clamp can populate long-lived conformational states (lifetimes > 1.0 s) and can switch between these long-lived states and the previously observed short-lived states. In addition, we find that clamp motions are increased in the presence of molecular crowding, are unchanged in the presence of elevated monovalent-cation concentrations, and are reduced in the presence of elevated divalent-cation concentrations. Finally, we find that RNAP bound to non-specific DNA predominantly exhibits a closed clamp conformation. Our results raise the possibility of additional regulatory checkpoints that could affect clamp dynamics and consequently could affect transcription and transcriptional regulation.

NIR Light-Mediated Mitochondrial RNA Modification for Cancer RNA Interference Therapeutics.

Mitochondrial RNA (mtRNA) plays a critical role in synthesis of mitochondrial proteins. Interfering mtRNA is a highly effective way to induce cell apoptosis. Herein, we report a near-infrared (NIR) light-mediated mitochondrial RNA modification approach for long-term imaging and effective suppression of tumors. A tumor-targetable NIR fluorescent probe f-CRI consisting of a cyclic RGD peptide, a NIR fluorophore IR780, and a singlet oxygen (1 O2 )-labile furan group for RNA modification was rationally designed and synthesized. This probe was demonstrated to dominantly accumulate in cellular mitochondria and could be covalently conjugated onto mtRNA upon 808 nm irradiation resulting in prolonged retention in tumors. More notably, this covalent modification of mtRNA by f-CRI could perturb the function of mitochondria leading to remarkable tumor suppression. We thus envision that our current approach would offer a potential approach for cancer RNA interference therapeutics.

Alkaline Phosphatase-Controllable and Red Light-Activated RNA Modification Approach for Precise Tumor Suppression.

RNA interference (RNAi) has proved to be a promising modality for disease treatment. However, the promise of conventional RNA therapeutics for clinical application is severely impeded by low delivery efficiency and susceptibility of RNAs to serum RNases. Therefore, developing advanced RNAi technology is an increasing demand for achieving precise medicine. Herein, for the first time, we propose an alkaline phosphatase (ALP)-controllable and red light-activated RNA modification (ALARM) approach for anti-tumor therapeutic application. An ALP-responsive NIR fluorogenic probe f-RCP consisting of a tumor-targeting cyclic RGD peptide, an ALP-activated photosensitizer CyOP, and an 1O2-susceptible furan module for RNA modification was rationally designed and synthesized. Studies have demonstrated that f-RCP can specifically target to liver carcinoma HepG2 cells and spontaneously emit activated NIR/photoacoustic signals upon cleavage by the ALP enzyme, allowing for sensitive detection of ALP-positive tumors. More notably, we surprisingly found that the capability of f-RCP producing singlet oxygen (1O2) under red light irradiation could be simultaneously unlocked, which can ignite the covalent cyclization reaction between furan and nucleobases of intracellular RNA molecules, leading to significant mitochondrial damage and severe apoptosis of tumor cells, in consequence realizing efficient tumor suppression. Most importantly, the potential therapeutic mechanism was first explored on the transcriptomic level. This delicate ALARM strategy may open up new insights into cancer gene therapy.

In Vivo Quantitative Assessment of a Radiation Dose Based on Ratiometric Photoacoustic Imaging of Tumor Apoptosis.

Accurately assessing the radiation level of tumors and surrounding tissues is of great significance for the optimization of clinical therapeutic interventions as well as minimizing the radiation-induced side effects. Therefore, the development of noninvasive and sensitive biological dosimeters is vital to achieve quantitative detection of a radiation dose in a living system. Herein, as a proof of concept, we report a tumor-targeted and caspase-3-activatable NIR fluorogenic probe AcDEVD-Cy-RGD consisting of a hemicyanine fluorophore as a signal reporter, a caspase-3 specific Asp-Glu-Val-Asp (DEVD) peptide, and a cyclic Arg-Gly-Asp peptide (cRGD) for tumor targeting. Upon cleavage with activated caspase-3, this probe not only displays the lighted-up NIR fluorescence, but also ratiometric photoacoustic (PA710/PA680) signals concurrently in a caspase-3 concentration-dependent manner, allowing for sensitive and quantitative detection of caspase-3 activity through both fluorescence and PA imaging, which provides the possibility for real-time monitoring of tumor cell apoptosis in a living system. More notably, we utilized this probe to successfully realize the direct visualization of tumor response to chemo- or radiotherapy and, for the first time, achieve the accurate estimation of radiation doses imparted to the tumors. We thus believe that our current strategy would offer an attractive and valuable means for the precise assessment of locally delivered radiation doses in various clinical settings.

The time-resolved atomic, molecular and optical science instrument at the Linac Coherent Light Source.

The newly constructed time-resolved atomic, molecular and optical science instrument (TMO) is configured to take full advantage of both linear accelerators at SLAC National Accelerator Laboratory, the copper accelerator operating at a repetition rate of 120 Hz providing high per-pulse energy as well as the superconducting accelerator operating at a repetition rate of about 1 MHz providing high average intensity. Both accelerators power a soft X-ray free-electron laser with the new variable-gap undulator section. With this flexible light source, TMO supports many experimental techniques not previously available at LCLS and will have two X-ray beam focus spots in line. Thereby, TMO supports atomic, molecular and optical, strong-field and nonlinear science and will also host a designated new dynamic reaction microscope with a sub-micrometer X-ray focus spot. The flexible instrument design is optimized for studying ultrafast electronic and molecular phenomena and can take full advantage of the sub-femtosecond soft X-ray pulse generation program.

cGAN-assisted imaging through stationary scattering media.

Analyzing images taken through scattering media is challenging, owing to speckle decorrelations from perturbations in the media. For in-line imaging modalities, which are appealing because they are compact, require no moving parts, and are robust, negating the effects of such scattering becomes particularly challenging. Here we explore the use of conditional generative adversarial networks (cGANs) to mitigate the effects of the additional scatterers in in-line geometries, including digital holographic microscopy. Using light scattering simulations and experiments on objects of interest with and without additional scatterers, we find that cGANs can be quickly trained with minuscule datasets and can also efficiently learn the one-to-one statistical mapping between the cross-domain input-output image pairs. Importantly, the output images are faithful enough to enable quantitative feature extraction. We also show that with rapid training using only 20 image pairs, it is possible to negate this undesired scattering to accurately localize diffraction-limited impulses with high spatial accuracy, therefore transforming a shift variant system to a linear shift invariant (LSI) system.

Subtle changes in pH affect the packing and robustness of fatty acid bilayers.

Connecting molecular interactions to emergent properties is a goal of physical chemistry, self-assembly, and soft matter science. We show that for fatty acid bilayers, vesicle rupture tension, and permeability to water and ions are coupled to pH via alterations to lipid packing. A change in pH of one, for example, can halve the rupture tension of oleic acid membranes, an effect that is comparable to increasing lipid unsaturation in phospholipid systems. We use both experiments and molecular dynamics simulations to reveal that a subtle increase in pH can lead to increased water penetration, ion permeability, pore formation rates, and membrane disorder. For changes in membrane water content, oleic acid membranes appear to be more than a million times more sensitive to protons than to sodium ions. The work has implications for systems in which fatty acids are likely to be found, for example in the primitive cells on early Earth, biological membranes especially during digestion, and other biomaterials.

Alterations of monoamine neurotransmitters, HPA-axis hormones, and inflammation cytokines in reserpine-induced hyperalgesia and depression comorbidity rat model.

BACKGROUND: Pain and depression often occur simultaneously, but the mechanism of this condition is still unclear. METHODS: The aim of this study was to examine the alterations of monoamine neurotransmitters, hypothalamic-pituitary-adrenal (HPA) axis hormones, and inflammation cytokines in hyperalgesia and depression comorbidities. The reserpine-induced "Sprague Dawley" (SD) rat models were used, and the concentrations of monoamine neurotransmitters serotonin (5-HT), norepinephrine (NE), dopamine (DA), and their metabolic products 5-hydroxyindoleacetic acid (5-HIAA), Homovanillic acid (HVA), 3,4-Dihydroxyphenylacetic acid (DOPAC) in raphe nucleus region were tested by High Performance Liquid Chromatography (HPLC). Serum levels of Adrenocorticotropic Hormone (ACTH), Cortisol (CORT), and inflammatory cytokines interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-4, IL-10 were assessed by enzyme linked immunosorbent assay. RESULTS: Repeated reserpine injection induced hyperalgesia and depressive behaviors with decreased sucrose preference and horizontal movement distance, and increased immobility time in forced swimming test. The concentrations of 5-HT and NE in raphe nucleus, and ACTH and CORT in serum were elevated in the model group. And the model group showed increases in serum IL-1ß and IL-6, and decrease in serum IL-10. CONCLUSION: More research in these areas is needed to understand the pathogenesis of the disease, so as to find more and better therapeutic targets.

A tetrapeptide class of biased analgesics from an Australian fungus targets the µ-opioid receptor.

An Australian estuarine isolate of Penicillium sp. MST-MF667 yielded 3 tetrapeptides named the bilaids with an unusual alternating LDLD chirality. Given their resemblance to known short peptide opioid agonists, we elucidated that they were weak (Ki low micromolar) µ-opioid agonists, which led to the design of bilorphin, a potent and selective µ-opioid receptor (MOPr) agonist (Ki 1.1 nM). In sharp contrast to all-natural product opioid peptides that efficaciously recruit ß-arrestin, bilorphin is G protein biased, weakly phosphorylating the MOPr and marginally recruiting ß-arrestin, with no receptor internalization. Importantly, bilorphin exhibits a similar G protein bias to oliceridine, a small nonpeptide with improved overdose safety. Molecular dynamics simulations of bilorphin and the strongly arrestin-biased endomorphin-2 with the MOPr indicate distinct receptor interactions and receptor conformations that could underlie their large differences in bias. Whereas bilorphin is systemically inactive, a glycosylated analog, bilactorphin, is orally active with similar in vivo potency to morphine. Bilorphin is both a unique molecular tool that enhances understanding of MOPr biased signaling and a promising lead in the development of next generation analgesics.

Defining Belonging and Its Association to Binge Drinking among College Students.

Objective: This study investigated the relationship between the students' combined belonging and binge drinking. Combined belonging was defined as a combination of both subjective (perceived belonging) and objective (participation in school activities) measures of belonging. Participants: The sample included 33,360 college students enrolled in U.S. States collegiate institutions. Methods: Data were obtained from an online survey through the Healthy Minds Study from 2018 to 2019. Logistic regression models estimated odds ratios and corresponding 95% confidence intervals. Results: Overall, 39.3% of students met criteria for binge drinking. Combined belonging had the highest odds of binge drinking compared to their counterparts. Being 21 and 22 years of age was the strongest risk factor for binge drinking. Conclusions: Interventions should be tailored to include objective and subjective measures of belonging to effectively reduce college binge drinking.

ASPP2 inhibits hepatitis B virus replication by preventing nucleus translocation of HSF1 and attenuating the transactivation of ATG7.

Hepatitis B virus (HBV) is a kind of virus with the capability to induce autophagy, thereby facilitating its replication. Reducing hepatocyte autophagy is proved to be a useful way to inhibit HBV replication. Herein, we reported that p53-binding protein 2 (apoptosis-stimulating protein of p53-2, ASPP2) could attenuate HBV-induced hepatocyte autophagy in a p53-independent manner. Mechanistically, overexpressed ASPP2 binds to HSF1 in cytoplasm of HBV-infected cells, which prevents the translocation of HSF1 to nuclei, thereby inhibiting the transactivation of Atg7. By regulating the transcription of Atg7, ASPP2 reduces hepatocyte autophagy, thereby inhibiting HBV replication. Therefore, ASPP2 is a key regulator of cell autophagy, and overexpression of ASPP2 could be a novel method to inhibit HBV replication in hepatocytes.

Thermally Driven Membrane Phase Transitions Enable Content Reshuffling in Primitive Cells.

Self-assembling single-chain amphiphiles available in the prebiotic environment likely played a fundamental role in the advent of primitive cell cycles. However, the instability of prebiotic fatty acid-based membranes to temperature and pH seems to suggest that primitive cells could only host prebiotically relevant processes in a narrow range of nonfluctuating environmental conditions. Here we propose that membrane phase transitions, driven by environmental fluctuations, enabled the generation of daughter protocells with reshuffled content. A reversible membrane-to-oil phase transition accounts for the dissolution of fatty acid-based vesicles at high temperatures and the concomitant release of protocellular content. At low temperatures, fatty acid bilayers reassemble and encapsulate reshuffled material in a new cohort of protocells. Notably, we find that our disassembly/reassembly cycle drives the emergence of functional RNA-containing primitive cells from parent nonfunctional compartments. Thus, by exploiting the intrinsic instability of prebiotic fatty acid vesicles, our results point at an environmentally driven tunable prebiotic process, which supports the release and reshuffling of oligonucleotides and membrane components, potentially leading to a new generation of protocells with superior traits. In the absence of protocellular transport machinery, the environmentally driven disassembly/assembly cycle proposed herein would have plausibly supported protocellular content reshuffling transmitted to primitive cell progeny, hinting at a potential mechanism important to initiate Darwinian evolution of early life forms.