Using an ER-specific optogenetic mechanostimulator to understand the mechanosensitivity of the endoplasmic reticulum.

The ability of cells to perceive and respond to mechanical cues is essential for numerous biological activities. Emerging evidence indicates important contributions of organelles to cellular mechanosensitivity and mechanotransduction. However, whether and how the endoplasmic reticulum (ER) senses and reacts to mechanical forces remains elusive. To fill the knowledge gap, after developing a light-inducible ER-specific mechanostimulator (LIMER), we identify that mechanostimulation of ER elicits a transient, rapid efflux of Ca2+ from ER in monkey kidney COS-7 cells, which is dependent on the cation channels transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and polycystin-2 (PKD2) in an additive manner. This ER Ca2+ release can be repeatedly stimulated and tuned by varying the intensity and duration of force application. Moreover, ER-specific mechanostimulation inhibits ER-to-Golgi trafficking. Sustained mechanostimuli increase the levels of binding-immunoglobulin protein (BiP) expression and phosphorylated eIF2α, two markers for ER stress. Our results provide direct evidence for ER mechanosensitivity and tight mechanoregulation of ER functions, placing ER as an important player on the intricate map of cellular mechanotransduction.

Higher disease burden and lower utilization in mongolian with breast cancer: a 9-year retrospective cohort study of 18.19 million adults in China.

BACKGROUND: Whether health inequalities of disease burden and medical utilization exist by ethnicity in Asian breast cancer (BC) patients remains unclear. We aim to measure ethnic disparities in disease burden and utilization among Mongolian and Han female breast cancer patients in China. MATERIALS AND METHODS: Based on data extracted from Inner Mongolia Regional Health Information Platform, a retrospective cohort study was established during 2012-2021. Disease burden including incidence, 5-year prevalence, mortality, survival rate, and medical cost were analyzed and compared between Han and Mongolian patients. RESULTS: A total of 34,878 female patients (mean [SD] age, 52.34 [10.93] years) were included among 18.19 million Chinese, and 4,315 [12.03%] participants were Mongolian. Age-standardized rates of incidence are 32.68 (95% CI: 20.39-44.98) per 100,000. Higher age-specific incidence and 5-year prevalence were observed in Mongolian than in Han. The cost of breast cancer annually per capita was significantly lower for Mongolian than Han in FBC ($1,948.43 [590.11-4 776.42] vs. $2,227.35 [686.65-5,929.59], P<0.001). Mongolian females showed higher all-cause mortality (30.92, [95% CI: 28.15-33.89] vs. 27.78, [95% CI: 26.77-28.83] per 1,000, P=0.036) and breast cancer-specific mortality (18.78, [95% CI: 16.64-21.13] vs. 15.22, [95% CI: 14.47-16.00] per 1,000, P=0.002) than Han females. After adjusting covariates, Mongolian were associated with increased all-cause mortality (HR, 1.21, [95% CI, 1.09-1.34]; P<0.001) and breast cancer-specific mortality (HR, 1.31, [95% CI, 1.14-1.49]; P<0.001). CONCLUSION: The findings of this cohort study highlight a higher level of disease burden with unmet medical demand in Mongolian patients, suggesting that more practical efforts should be made for the minority. Further research is needed to explore the concrete mechanisms of the disparities as well as eliminate health disproportion.

The relationship between accommodation, binocular function and myopia progression in myopic children wearing orthokeratology lenses.

PURPOSE: To determine the relationship between changes in accommodative and binocular function with myopia progression in myopic children over a two-year follow-up period, and to determine when changes in visual functions stabilized after switching from spectacles to orthokeratology (Ortho-K). METHODS: This prospective, self-controlled study followed thirty-six participants (aged 8-14 years) for two years after they switched from spectacles to Ortho-K. Accommodative and binocular function were assessed prior to and 1, 3, 6, 12, 18 and 24 months after commencing Ortho-K. Measurements included accommodative amplitude, accommodative response, accommodative facility, accommodative convergence/accommodation (AC/A), ocular alignment, positive relative accommodation (PRA), negative relative accommodation (NRA), horizontal vergence range, reading ability and stereoacuity. Myopia progression was quantified by the change in axial length. RESULTS: Ocular alignment, monocular and binocular accommodative facility, and PRA stabilized after 1 month. The distance blur point in the convergence range, the distance break and recovery point in the divergence range, accommodative amplitude, calculated AC/A, stereoacuity and reading ability stabilized within 6 months. After two years of Ortho-K, NRA significantly increased (p = 0.044), while it showed no significant difference after one-year of lens wear (p = 0.49). The distance break point in the convergence range showed no significant difference (p = 0.20), but significantly decreased after one-year (p = 0.005). There were no significant correlations between the change in axial length with changes in accommodative or binocular function (p > 0.05). CONCLUSION: Accommodative and binocular function changed significantly after switching from spectacles to Ortho-K and most of the parameters stabilized within the first 6 months. There was no association between the change in accommodative or binocular function and myopia progression.

Force-induced tail-autotomy mitochondrial fission and biogenesis of matrix-excluded mitochondrial-derived vesicles for quality control.

Mitochondria constantly fuse and divide for mitochondrial inheritance and functions. Here, we identified a distinct type of naturally occurring fission, tail-autotomy fission, wherein a tail-like thin tubule protrudes from the mitochondrial body and disconnects, resembling autotomy. Next, utilizing an optogenetic mitochondria-specific mechanostimulator, we revealed that mechanical tensile force drives tail-autotomy fission. This force-induced fission involves DRP1/MFF and endoplasmic reticulum tubule wrapping. It redistributes mitochondrial DNA, producing mitochondrial fragments with or without mitochondrial DNA for different fates. Moreover, tensile force can decouple outer and inner mitochondrial membranes, pulling out matrix-excluded tubule segments. Subsequent tail-autotomy fission separates the matrix-excluded tubule segments into matrix-excluded mitochondrial-derived vesicles (MDVs) which recruit Parkin and LC3B, indicating the unique role of tail-autotomy fission in segregating only outer membrane components for mitophagy. Sustained force promotes fission and MDV biogenesis more effectively than transient one. Our results uncover a mechanistically and functionally distinct type of fission and unveil the role of tensile forces in modulating fission and MDV biogenesis for quality control, underscoring the heterogeneity of fission and mechanoregulation of mitochondrial dynamics.

Carbon Nanofibrous Aerogels Derived from Electrospun Polyimide for Multifunctional Piezoresistive Sensors.

The fabrication of carbon aerogels with ultralow density, high electrical conductivity, and ultraelasticity still remains substantial challenges. This study utilizes electrospun polyimide aerogel as the source to fabricate flexible carbon nanofibrous aerogel (PI-CNA) capable of multifunctional applications. The lightweight PI-CNA based piezoresistive sensor shows a wide linear range (0-217 kPa), rapid response/recovery time, and fatigue resistance (12,000 cycles). More importantly, the superior pressure sensing enables the PI-CNA for all-range healthcare sensing, including pulse monitoring, physiological activity detection, speech recognition, and gait recognition. Moreover, the EMI SE and the A coefficient of the PI-CNA reach 45 dB and 0.62, respectively, indicating the outstanding absorption dominated EMI shielding effects due to the multiple reflections and absorption. Furthermore, PI-CNA exhibits satisfying Joule heating performance up to 120 °C with rapid response time (10-30 s) under low supply voltages (1.5-5 V) and possesses sufficient heating reliability and repeatability in long-term repeated heating/cooling cycles. The fabricated PI-CNA shows significant potential applications in wearable technologies, energy conversion, electronic skin, and artificial intelligence.

Corrective mechanisms of motion extrapolation.

Transmission and processing of sensory information in the visual system takes time. For motion perception, our brain can overcome this intrinsic neural delay through extrapolation mechanisms and accurately predict the current position of a continuously moving object. But how does the system behave when the motion abruptly changes and the prediction becomes wrong? Here we address this question by studying the perceived position of a moving object with various abrupt motion changes by human observers. We developed a task in which a bar is monotonously moving horizontally, and then motion suddenly stops, reverses, or disappears-then-reverses around two vertical stationary reference lines. Our results showed that participants overestimated the position of the stopping bar but did not perceive an overshoot in the motion reversal condition. When a temporal gap was added at the reverse point, the perceptual overshoot of the end point scaled with the gap durations. Our model suggests that the overestimation of the object position when it disappears is not linear as a function of its speeds but gradually fades out. These results can thus be reconciled in a single process where there is an interplay of the cortical motion prediction mechanisms and the late sensory transient visual inputs.

Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment.

Amultifunctional liposomal polydopamine nanoparticle (MPM@Lipo) was designed in this study, to combine chemotherapy, photothermal therapy (PTT) and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis (RA) treatment. MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia, thus contributing to the repolarization of M1 macrophages into M2 phenotype. Furthermore, MPM@Lipo could accumulate at inflammatory joints, inhibit the production of inflammatory factors, and protect cartilage in vivo, effectively alleviating RA progression in a rat adjuvant-induced arthritis model. Moreover, upon laser irradiation, MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen, resulting in excellent RA treatment effects. Overall, the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.

Binocular function in the aging visual system: fusion, suppression, and stereoacuity.

Introduction: Changes in vision that occur in normal healthy aging can be seen in fundamental measures of monocular vision. However, the nature of the changes in binocular vision with age remain unclear. Methods: A total of 28 older (53-66 years) and 28 younger adults (20-31 years) were enrolled in this study. We performed a battery of tests to assess differences in monocular contrast thresholds and various binocular visual functions including dichoptic masking weight and strength, the binocular balance point for fused stimuli, and stereoacuity in the aging and control groups. Results: Aging significantly increased monocular contrast thresholds (p < 0.001). Although this suggests that aging reduces the effective "input gain" to vision, we also found a significantly elevated contribution of those weaker signals to interocular suppression (p < 0.001). Consequently, there was no significant net difference in the strength of interocular suppression (p = 0.065). We did not find a significant difference of absolute balance point between the two groups (p = 0.090). Lastly, the mean stereoacuity was worse in the older group compared to the younger group (p = 0.002). Discussion: Our findings confirm previous results showing differences in contrast sensitivity and stereoacuity with aging. Furthermore, we find a change in interocular suppression that is a possible consequence of the change in contrast sensitivity. It is suggestive of a cortical system that maintains a homeostatic balance in interocular suppression across the lifespan.

Role of corticosteroids in the treatment of critically ill sepsis patients: a meta-analysis review.

OBJECTIVE: It was to systematically evaluate the effect of corticosteroids on 28d all-cause mortality (ACM), in-hospital death rate, and ICU death rate in critically ill sepsis patients. METHODS: PubMed, Embase, and Medline databases were used to screen the published literatures on the therapeutic effect of corticosteroids in the treatment of critically ill sepsis patients. After evaluating the quality of the included literatures, RevMan 5.3 software was used for meta-analysis. 4524 literatures regarding the application of corticosteroids to treat critically ill sepsis patients were preliminarily searched. After screening was carried out, 9 literatures were finally included. 2,850 patients were treated with corticosteroids and 2867 patients were treated with placebo. RESULTS: The meta-analysis of the effect of corticosteroids versus placebo on 28dACM showed [OR = 0.87, 95% CI 0.78-0.98, Z = 2.22, P = 0.03], P < 0.05; the meta-analysis of the outcome of corticosteroids versus placebo on ICU death rate showed [OR = 0.77, 95% CI 0.63-0.94, Z = 2.60, P = 0.009], P < 0.05; and the meta-analysis of the effect of corticosteroids versus placebo on in-hospital death rate showed [OR = 0.80, 95% CI 0.66-0.96, Z = 2.34, P = 0.002], P < 0.05. CONCLUSION: In summary, corticosteroids can reduce the death rate of critically ill sepsis patients to a certain extent and have good clinical application value.

Glutamatergic Projection from the Ventral Tegmental Area to the Zona Incerta Regulates Fear Response.

Innate defensive behavior is important for animal survival. The Vglut2+ neurons in the ventral tegmental area (VTA) have been demonstrated to play important roles in innate defensive behaviors, but the neural circuit mechanism is still unclear. Here, we find that VTA - zona incerta (ZI) glutamatergic projection is involved in regulating innate fear responses. Combining calcium signal recording and chemogentics, we find that VTA-Vglut2+ neurons respond to foot shock stimulus. Inhibition of VTA-Vglut2+ neurons reduces foot shock-evoked freezing, while chemogentic activation of these neurons results in an enhanced fear response. Using viral tracing and immunofluorescence, we show that VTA - Vglut2+ neurons send direct excitatory outputs to the ZI. Moreover, we find that the activity of VTAVglut2 - ZI projection is pivotal in modulating fear response. Together, our study reveals a new VTA - ZI glutamatergic circuit in mediating innate fear response and provides a potential target for treating post-traumatic stress disorder.

Ecological evolution of algae in connected reservoirs under the influence of water transfer: Algal density, community structure, and assembly processes.

Reservoir connectivity provides a solution for regional water shortages. Understanding the water quality of reservoirs and the response of algal communities to water transfer could provide the basis for a long-term evolutionary model of reservoirs. In this study, a water-algal community model was established to study the effects of water transfer on water quality and algal communities in reservoirs. The results showed that water transfer significantly decreased total nitrogen and nitrate concentrations. However, the water transfer resulted in an increase in the CODMn concentration and conductivity in the receiving reservoir. Additionally, the algal density and chlorophyll-a (chl-a) concentration showed an increase with water transfer. Bacillariophyta, Cyanophyta, and Chlorophyta were the dominant algal phyllum in all three reservoirs. Water transfer induced the evolution of the algal community by driving changes in the chemical parameters of the receiving reservoir and led to more complex relationships within the algal community. The effects of stochastic processes on algal communities were also enhanced in the receiving reservoirs. These results provide specific information for water quality safety management and eutrophication prevention in connected reservoirs.

Ultrasensitive Optical Detection and Elimination of Residual Microtumors with a Postoperative Implantable Hydrogel Sensor for Preventing Cancer Recurrence.

In vivo optical imaging of trace biomarkers in residual microtumors holds significant promise for cancer prognosis but poses a formidable challenge. Here, a novel hydrogel sensor is designed for ultrasensitive and specific imaging of the elusive biomarker. This hydrogel sensor seamlessly integrates a molecular beacon nanoprobe with fibroblasts, offering both high tissue retention capability and an impressive signal-to-noise ratio for imaging. Signal amplification is accomplished through exonuclease I-mediated biomarker recycling. The resulting hydrogel sensor sensitively detects the biomarker carcinoembryonic antigen with a detection limit of 1.8 pg mL-1 in test tubes. Moreover, it successfully identifies residual cancer nodules with a median diameter of less than 2 mm in mice bearing partially removed primary triple-negative breast carcinomas (4T1). Notably, this hydrogel sensor is proven effective for the sensitive diagnosis of invasive tumors in post-surgical mice with infiltrating 4T1 cells, leveraging the role of fibroblasts in locally enriching tumor cells. Furthermore, the residual microtumor is rapidly photothermal ablation by polydopamine-based nanoprobe under the guidance of visualization, achieving ≈100% suppression of tumor recurrence and lung metastasis. This work offers a promising alternative strategy for visually detecting residual microtumors, potentially enhancing the prognosis of cancer patients following surgical interventions.

Screening of the Active Substances for the Assessment of Walnut Kernel in the Treatment of Scopolamine-Induced AD Animals.

SCOPE: Alzheimer's disease (AD) has been a challenge and hotspot in the field of neuroscience research due to the high morbidity. As we all know, walnut kernel (WK) ingestion has been linked to benefits to brain health and has the function of improving memory. This study follows the AD model induced by scopolamine to reveal the active fractions and substances of walnut in the treatment of AD. METHODS AND RESULTS: The histopathological analysis and brain tissue biochemistry assay are revealed the active fractions of WK, and this result determines that walnut kernel organic acids have significant therapeutic effect on AD. The strategy of studying ingredients pointed at lesions is integrated to ascertain the selected brain-targeted effective substances of WK for blood-brain barrier by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry, and a total of eight organic acids are figured out definite absorptivity in rat brains. Finally, the binding interaction between the effective substances and target proteins is analyzed by molecular docking, and the main function related active markers are ascertained as glansreginin A, glansreginic acid, ellagic acid, and ellagic acid 4-O-xyloside. CONCLUSIONS: The comprehensive process is helpful to the clinical application of WK as a promising cholinesterase inhibitors for nutritional intervention.

"They're scared that somebody's gonna judge them": Female African American youth in Foster Care's perspectives on sexual and reproductive health communication with caregivers.

BACKGROUND: Obtaining accurate information is critical for youth's sexual and reproductive health (SRH). Youth not in foster care often learn about SRH from their biological parents. Separated from their biological parents, youth in care depend on healthcare providers and caregivers for SRH information. However, they often receive insufficient information and feel unsupported in meeting their needs for SRH information. PURPOSE: This study explored female African American adolescents in foster care's perspectives on effective SRH communication with caregivers to help them avoid sexual risks. METHODS: A qualitative study was conducted using semi-structured interviews. We used purposive sampling to recruit 16 adolescents aged 18 to 20 years old with a history of foster care placement. The transcribed interviews underwent inductive thematic analysis. The Positive Youth Development theory underpinned this research. RESULTS: Two prominent themes emerged: establishing a relationship and preferred communication approach. Youth reported that for caregivers to engage in effective SRH communication, they must first establish a relationship by being aware of the youth's childhood trauma, building trust, having patience, and being vulnerable. Youth also appreciated caregivers who ensured comfortability and were honest and straightforward. DISCUSSION: Caregivers should be trained on adverse childhood experiences, trauma-informed approaches, SRH knowledge, and communication. IMPLICATIONS TO PRACTICE: Healthcare providers should make use of the time spent with youth and discuss SRH topics during clinical encounters. This time spent with youth may be their only chance to obtain accurate SRH information. Youth's perspectives regarding communication about SRH should be implemented in future SRH communication interventions.

The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx.

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca2+ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca2+ ([Ca2+]i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca2+]i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca2+]i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca2+]i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca2+ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca2+]i.

Correlation of IVIM/DKI Parameters with Hypoxia Biomarkers in Fibrosarcoma Murine Models: Direct Control of MRI and Pathological Sections.

RATIONALE AND OBJECTIVES: To investigate whether intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) parameters correlate with hypoxia biomarkers, namely hypoxia inducible factor-1ɑ (HIF-1ɑ), carbonic anhydrase IX (CAIX), and pimonidazole (PIMO), in fibrosarcoma (FS) murine models. MATERIALS AND METHODS: A model of 30 FS nude mice was established. All mice underwent magnetic resonance imaging (MRI) scans after which the IVIM (standard apparent diffusion coefficient [standard ADC], pure diffusion coefficient [D], pseudo-diffusion coefficient [D*], and perfusion fraction [f]) and DKI parameters (mean diffusion [MD], mean kurtosis [MK]) were obtained. Based on an MRI-pathology controlled method, correlations between each MRI parameter and hypoxia biomarkers were assessed by Pearson or Spearman tests. An independent sample t-test or Wilcoxon's rank sum test, and receiver operating characteristic curves were used to identify whether MRI parameters could differentiate between high and low expressions of hypoxia biomarkers. RESULTS: The IVIM/DKI parameters showed varying degrees of correlation with HIF-1α, CAIX, and PIMO expression. Among them, the D, f, and MK values could confirm HIF-1α expression, while D, f, and MK values could assess CAIX expression. Finally, standard D and MK values could evaluate PIMO expression levels. CONCLUSION: IVIM and DKI parameters can be used to reflect hypoxic biomarkers of FS and have the potential to detect tumor hypoxia.

Cubosomes-assisted transdermal delivery of doxorubicin and indocyanine green for chemo-photothermal combination therapy of melanoma.

Melanoma is a highly aggressive form of skin cancer with limited therapeutic options. Chemo-photothermal combination therapy has demonstrated potential for effectively treating melanoma, and transdermal administration is considered the optimal route for treating skin diseases due to its ability to bypass first-pass metabolism and enhance drug concentration. However, the stratum corneum presents a formidable challenge as a significant barrier to drug penetration in transdermal drug delivery. Lipid-nanocarriers, particularly cubosomes, have been demonstrated to possess significant potential in augmenting drug permeation across the stratum corneum. Herein, cubosomes co-loaded with doxorubicin (DOX, a chemotherapeutic drug) and indocyanine green (ICG, a photothermal agent) (DOX-ICG-cubo) transdermal drug delivery system was developed to enhance the therapeutic efficiency of melanoma by improving drug permeation. The DOX-ICG-cubo showed high encapsulation efficiency of both DOX and ICG, and exhibited good stability under physiological conditions. In addition, the unique cubic structure of the DOX-ICG-cubo was confirmed through transmission electron microscopy (TEM) images, polarizing microscopy, and small angle X-ray scattering (SAXS). The DOX-ICG-cubo presented high photothermal conversion efficiency, as well as pH and thermo-responsive DOX release. Notably, the DOX-ICG-cubo exhibited enhanced drug permeation efficiency, good biocompatibility, and improved in vivo anti-melanoma efficacy through the synergistic effects of chemo-photothermal therapy. In conclusion, DOX-ICG-cubo presented a promising strategy for melanoma treatment.

Two parallel medial prefrontal cortex-amygdala pathways mediate memory deficits via glutamatergic projection in surgery mice.

The neural circuit mechanisms underlying postoperative cognitive dysfunction (POCD) remain elusive. We hypothesized that projections from the medial prefrontal cortex (mPFC) to the amygdala are involved in POCD. A mouse model of POCD in which isoflurane (1.5%) combined with laparotomy was used. Virally assisted tracing techniques were used to label the relevant pathways. Fear conditioning, immunofluorescence, whole-cell patch-clamp recordings, and chemogenetic and optogenetic techniques were applied to investigate the role of mPFC-amygdala projections in POCD. We find that surgery impairs memory consolidation but not retrieval of consolidated memories. In POCD mice, the glutamatergic pathway from the prelimbic cortex to the basolateral amygdala (PL-BLA) shows reduced activity, whereas the glutamatergic pathway from the infralimbic cortex to the basomedial amygdala (IL-BMA) shows enhanced activity. Our study indicates that the hypoactivity in the PL-BLA pathway interrupts memory consolidation, whereas the hyperactivity in the IL-BMA promotes memory extinction, in POCD mice.

Characteristics of methane emissions from alpine thermokarst lakes on the Tibetan Plateau.

Understanding methane (CH4) emission from thermokarst lakes is crucial for predicting the impacts of abrupt thaw on the permafrost carbon-climate feedback. However, observational evidence, especially from high-altitude permafrost regions, is still scarce. Here, by combining field surveys, radio- and stable-carbon isotopic analyses, and metagenomic sequencing, we present multiple characteristics of CH4 emissions from 120 thermokarst lakes in 30 clusters along a 1100 km transect on the Tibetan Plateau. We find that thermokarst lakes have high CH4 emissions during the ice-free period (13.4 ± 1.5 mmol m-2 d-1; mean ± standard error) across this alpine permafrost region. Ebullition constitutes 84% of CH4 emissions, which are fueled primarily by young carbon decomposition through the hydrogenotrophic pathway. The relative abundances of methanogenic genes correspond to the observed CH4 fluxes. Overall, multiple parameters obtained in this study provide benchmarks for better predicting the strength of permafrost carbon-climate feedback in high-altitude permafrost regions.

In situ architecture and membrane fusion of SARS-CoV-2 Delta variant.

Among the current five Variants of Concern, infections caused by SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, the architecture of intact Delta virions remains veiled. Moreover, pieces of molecular evidence for the detailed mechanism of S-mediated membrane fusion are missing. Here, we showed the pleomorphic nature of Delta virions from electron beam inactivated samples and reported the in situ structure and distribution of S on the authentic Delta variant. We also captured the virus-virus fusion events, which provided pieces of structural evidence for Delta's attenuated dependency on cellular factors for fusion activation, and proposed a model of S-mediated membrane fusion. Besides, site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S than that of the WT S. Together, these results disclose distinctive factors of Delta being the most virulent SARS-CoV-2 variant.