A Broad-specificity Neutralizing Nanobody against Hepatitis E Virus Capsid Protein.

Hepatitis E virus (HEV) is a worldwide zoonotic and public health concern. The study of HEV biology is helpful for designing viral vaccines and drugs. Nanobodies have recently been considered appealing materials for viral biological research. In this study, a Bactrian camel was immunized with capsid proteins from different genotypes (1, 3, 4, and avian) of HEV. Then, a phage library (6.3 × 108 individual clones) was constructed using peripheral blood lymphocytes from the immunized camel, and 12 nanobodies against the truncated capsid protein of genotype 3 HEV (g3-p239) were screened. g3-p239-Nb55 can cross-react with different genotypes of HEV and block Kernow-C1/P6 HEV from infecting HepG2/C3A cells. To our knowledge, the epitope recognized by g3-p239-Nb55 was determined to be a novel conformational epitope located on the surface of viral particles and highly conserved among different mammalian HEV isolates. Next, to increase the affinity and half-life of the nanobody, it was displayed on the surface of ferritin, which can self-assemble into a 24-subunit nanocage, namely, fenobody-55. The affinities of fenobody-55 to g3-p239 were ∼20 times greater than those of g3-p239-Nb55. In addition, the half-life of fenobody-55 was nine times greater than that of g3-p239-Nb55. G3-p239-Nb55 and fenobody-55 can block p239 attachment and Kernow-C1/P6 infection of HepG2/C3A cells. Fenobody-55 can completely neutralize HEV infection in rabbits when it is preincubated with nonenveloped HEV particles. Our study reported a case in which a nanobody neutralized HEV infection by preincubation, identified a (to our knowledge) novel and conserved conformational epitope of HEV, and provided new material for researching HEV biology.

[Changes and influence factors of soil matrix infiltration in Chinese fir plantations with different stand ages in northern Guangxi]. / æ¡‚åŒ—åœ°åŒºä¸åŒæž—é¾„æ‰æœ¨äººå·¥æž—åœŸå£¤åŸºè´¨å ¥æ¸—å˜åŒ–åŠå½±å“å› ç´ .

Soil matrix infiltration is an important pathway for plantations to obtain water, which affects ecological benefits and water conservation function of plantations. The changes of soil matrix infiltration and its influencing factors in different growth stages of Chinese fir plantations remain unclear. We measured soil matrix infiltration process using a tension infiltrometer in Chinese fir plantations (5, 8, 11, and 15 years old) of Beijiang River Forest Farm in Rongshui, Guangxi, and analyzed soil basic physicochemical properties to identify the dominant factors influencing soil matrix infiltration. The results showed that initial infiltration rate, stable infiltration rate, and cumulative infiltration increased with stand ages. The ranges of different stand ages were 141-180 mm·h-1, 109-150 mm·h-1, and 188-251 mm, respectively. The initial infiltration rate, stable infiltration rate, and cumulative infiltration were significantly positively correlated with soil capillary porosity, soil organic matter, soil water stable macroaggregate, sand content, and clay content, while negatively correlated with soil bulk density and silt content. Early thinning had a positive effect on soil matrix infiltration, but thinning measures after 11 years did not enhance soil matrix infiltration further. Philip model was optimal for describing soil matrix infiltration process in this region. In conclusion, soil matrix infiltration capacity of Chinese fir plantations gradually increased from young to middle-aged stands, but matrix infiltration capacity tended to stabilize after 11 years old. Silt content and water stable macroaggregate were the dominant factors influencing matrix infiltration.

Hepatitis E virus ORF3 protein hijacking thioredoxin domain-containing protein 5 (TXNDC5) for its stability to promote viral particle release.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide, responsible for approximately 20 million infections annually. Among the three open reading frames (ORFs) of the HEV genome, the ORF3 protein is involved in virus release. However, the host proteins involved in HEV release need to be clarified. In this study, a host protein, thioredoxin domain-containing protein 5 (TXNDC5), interacted with the non-palmitoylated ORF3 protein by co-immunoprecipitation analysis. We determined that the overexpression or knockdown of TXNDC5 positively regulated HEV release from the host cells. The 17FCL19 mutation of the ORF3 protein lost the ability to interact with TXNDC5. The releasing amounts of HEV with the ORF3 mutation (FCL17-19SSP) were decreased compared with wild-type HEV. The overexpression of TXNDC5 can stabilize and increase ORF3 protein amounts, but not the TXNDC5 mutant with amino acids 1-88 deletion. Meanwhile, we determined that the function of TXNDC5 on the stabilization of ORF3 protein is independent of the Trx-like domains. Knockdown of TXNDC5 could lead to the degradation of ORF3 protein by the endoplasmic reticulum (ER)-associated protein degradation-proteasome system. However, the ORF3 protein cannot be degraded in the knockout-TXNDC5 stable cells, suggesting that it may hijack other proteins for its stabilization. Subsequently, we found that the other members of protein disulfide isomerase (PDI), including PDIA1, PDIA3, PDIA4, and PDIA6, can increase ORF3 protein amounts, and PDIA3 and PDIA6 interact with ORF3 protein. Collectively, our study suggested that HEV ORF3 protein can utilize TXNDC5 for its stability in ER to facilitate viral release. IMPORTANCE: Hepatitis E virus (HEV) infection is the leading cause of acute viral hepatitis worldwide. After the synthesis and modification in the cells, the mature ORF3 protein is essential for HEV release. However, the host protein involved in this process has yet to be determined. Here, we reported a novel host protein, thioredoxin domain-containing protein 5 (TXNDC5), as a chaperone, contributing to HEV release by facilitating ORF3 protein stability in the endoplasmic reticulum through interacting with non-palmitoylated ORF3 protein. However, we also found that in the knockout-TXNDC5 stable cell lines, the HEV ORF3 protein may hijack other proteins for its stabilization. For the first time, our study demonstrated the involvement of TXNDC5 in viral particle release. These findings provide some new insights into the process of the HEV life cycle, the interaction between HEV and host factors, and a new direction for antiviral design.

Anthropometric indicators may explain the high incidence of follicular lymphoma in Europeans: Results from a bidirectional two-sample two-step Mendelian randomisation.

BACKGROUND: Non-Hodgkin's lymphoma incidence rates vary between European and Asian populations. The reasons remain unclear. This two-sample two-step Mendelian randomisation (MR) study aimed to investigate the causal relationship between anthropometric indicators (AIs) and diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) and the possible mediating role of basal metabolic rate (BMR) in Europe. METHODS: We used the following AIs as exposures: body mass index (BMI), whole-body fat mass (WBFM), whole-body fat-free mass (WBFFM), waist circumference(WC), hip circumference(HC), standing height (SH), and weight(Wt). DLBCL and FL represented the outcomes, and BMR was a mediator. A two-sample MR analysis was performed to examine the association between AIs and DLBCL and FL onset. We performed reverse-MR analysis to determine whether DLBCL and FL interfered with the AIs. A two-step MR analysis was performed to determine whether BMR mediated the causality. FINDINGS: WBFFM and SH had causal relationships with FL. A causal association between AIs and DLBCL was not observed. Reverse-MR analysis indicated the causal relationships were not bidirectional. Two-step MR suggested BMR may mediate the causal effect of WBFFM and SH on FL. CONCLUSIONS: We observed a causal relationship between WBFFM and SH and the onset of FL in Europeans, Which may explain the high incidence of follicular lymphoma in Europeans.

A novel strategy for an anti-idiotype vaccine: nanobody mimicking neutralization epitope of porcine circovirus type 2.

Vaccination is the most effective method to protect humans and animals from diseases. Anti-idiotype vaccines are safer due to their absence of pathogens. However, the commercial production of traditional anti-idiotype vaccines using monoclonal and polyclonal antibodies (mAb and pAb) is complex and has a high failure rate. The present study designed a novel, simple, low-cost strategy for developing anti-idiotype vaccines with nanobody technology. We used porcine circovirus type 2 (PCV2) as a viral model, which can result in serious economic loss in the pig industry. The neutralizing mAb-1E7 (Ab1) against PCV2 capsid protein (PCV2-Cap) was immunized in the camel. And 12 nanobodies against mAb-1E7 were screened. Among them, Nb61 (Ab2) targeted the idiotype epitope of mAb-1E7 and blocked mAb-1E7's binding to PCV2-Cap. Additionally, a high-dose Nb61 vaccination can also protect mice and pigs from PCV2 infection. Epitope mapping showed that mAb-1E7 recognized the 75NINDFL80 of PCV2-Cap and 101NYNDFLG107 of Nb61. Subsequently, the mAb-3G4 (Ab3) against Nb61 was produced and can neutralize PCV2 infection in the PK-15 cells. Structure analysis showed that the amino acids of mAb-1E7 and mAb-3G4 respective binding to PCV2-Cap and Nb61 were also similar on the amino acids sequences and spatial conformation. Collectively, our study first provided a strategy for producing nanobody-based anti-idiotype vaccines and identified that anti-idiotype nanobodies could mimic the antigen on amino acids and structures. Importantly, as more and more neutralization mAbs against different pathogens are prepared, anti-idiotype nanobody vaccines can be easily produced against the disease with our strategy, especially for dangerous pathogens.IMPORTANCEAnti-idiotype vaccines utilize idiotype-anti-idiotype network theory, eliminating the need for external antigens as vaccine candidates. Especially for dangerous pathogens, they were safer because they did not contact the live pathogenic microorganisms. However, developing anti-idiotype vaccines with traditional monoclonal and polyclonal antibodies is complex and has a high failure rate. We present a novel, universal, simple, low-cost strategy for producing anti-idiotype vaccines with nanobody technology. Using a neutralization antibody against PCV2-Cap, a nanobody (Ab2) was successfully produced and could mimic the neutralizing epitope of PCV2-Cap. The nanobody can induce protective immune responses against PCV2 infection in mice and pigs. It highlighted that the anti-idiotype vaccine using nanobody has a very good application in the future, especially for dangerous pathogens.

Chinese expert consensus on imaging diagnosis of drug-resistant pulmonary tuberculosis.

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB.

Cortical perforation combined with Masquelet technique to treat extensive bone and soft tissue injury: A case report.

INTRODUCTION: We report a case of a serious traffic accident injury to the lower leg involving a large skin defect with the long bone exposed. In this situation, the usual intervention is flap transplantation after debridement and infection control by completely covering the wound. Flap transplantation has certain limitations; therefore, we chose the surgical strategy of cortical bone drilling-induced membrane technology (Masquelet technique). CASE PRESENTATION: A 28-year-old healthy man was injured in a car accident and presented to the local hospital with a large skin defect and exposed left lower leg long bone. After transfer to our hospital, the patient underwent repeated debridement and skin graft, a cortex borehole combined with bone cement cover, and ankle fusion. The patient achieved full recovery. CONCLUSION: From our experience in treating this case, we conclude that large skin defects, periosteal stripping, and bone exposure due to physical injury can be successfully treated with cortical perforation and the Masquelet technique so as to avoid flap transplantation. Therefore, this method can be used for large segment bone exposure.

Antimicrobial agent chloroxylenol targets ß­catenin­mediated Wnt signaling and exerts anticancer activity in colorectal cancer.

Chloroxylenol is the active ingredient of the antibacterial agent Dettol. The anticancer effect and underlying mechanisms of this compound and other common antimicrobial agents have not been clearly elucidated. In the present study, the effects of chloroxylenol, benzalkonium chloride, benzethonium chloride, triclosan and triclocarban on ß­catenin­mediated Wnt signaling in colorectal cancer were evaluated using the SuperTOPFlash reporter assay. It was demonstrated that chloroxylenol, but not the other antimicrobial agents tested, inhibited the Wnt/ß­catenin signaling pathway by decreasing the nuclear translocation of ß­catenin and disrupting ß­catenin/T­cell factor 4 complex, which resulted in the downregulation of the Wnt target genes Axin2, Survivin and Leucine­rich G protein­coupled receptor­5. Chloroxylenol effectively inhibited the viability, proliferation, migration and invasion, and sphere formation, and induced apoptosis in HCT116 and SW480 cells. Notably, chloroxylenol attenuated the growth of colorectal cancer in the MC38 cell xenograft model and inhibited organoid formation by the patient­derived cells. Chloroxylenol also demonstrated inhibitory effects on the stemness of colorectal cancer cells. The results of the present study demonstrated that chloroxylenol could exert anti­tumor activities in colorectal cancer by targeting the Wnt/ß­catenin signaling pathway, which provided an insight into its therapeutic potential as an anticancer agent.

[Summary of the best evidence for the energy and protein intake targets and calculation in critically ill patients].

OBJECTIVE: To evaluate and summarize the best evidence of energy and protein intake targets and calculation in adult critically ill patients, and to provide evidence-based basis for critical nutrition management. METHODS: Evidence related to energy and protein intake targets and calculation of adult critically ill patients, including guideline, expert consensus, systematic review and evidence summary, were systematically searched in PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Cochrane Library, UpToDate, BMJ Best Practice, Joanna Briggs Institute (JBI), Web of Science, SinoMed, Medive, China National Knowledge Infrastructure, Wanfang database, VIP database, Guidelines International Network (GIN), National Institute for Health and Care Excellence (NICE), National Guideline Clearinghouse (NGC), Registered Nurses Association of Ontario (RNAO), and Society of Critical Care Medicine (SCCM) from January 2012 to June 2022. Two researchers independently evaluated the quality of the included literatures using the JBI Evidence-based Health Care Center evaluation tool and the Appraisal of Clinical Practice Guidelines for Research and Evaluation II (AGREE II), extracted and summarized the best evidence for the nutritional intake goal and calculation of adult critically ill patients, and described the evidence. RESULTS: A total of 18 literatures were included, including 5 clinical guidelines, 8 expert consensus, 3 systematic reviews and 2 evidence summaries. After literature quality evaluation, 18 articles were all enrolled. The evidence was summarized from the four aspects, including energy target calculation method, dose body weight, energy and protein intake target, and calculation method, 24 pieces of the best evidence were finally formed. CONCLUSIONS: The best evidence of energy and protein intake targets and calculation for critically ill patients was summarized based on evidence-based. Clinical medical staff can choose indirect calorimetry to calculate energy goals when equipment is available. Patient's height, body weight should be recorded accurately, dose body weight can be determined by body mass index (BMI). Meanwhile, blood urea nitrogen (BUN) loss, fat-free body weight, simple formulas and other methods should be used to continuously evaluate and adjust protein intake targets, to achieve the purpose of optimizing intensive nutrition support.

Microecological health assessment of water environment and sediment based on metagenomics: a case study of Guixi River in Chongqing, China.

River sediment is vital in containing water pollution and strengthening water remediation. This paper has conducted a study on the microecological health assessment of the sediment and water body of Guixi River in Dianjiang, Chongqing, China, using metagenomics sequencing and microbial biological integrity index (M-IBI) technology. The analysis of physical and chemical characteristics shows that the concentration of TN varies from 2.62 to 9.76 mg/L in each sampling section, and the eutrophication of the water body is relatively severe. The proportion of Cyanobacteria in the sampling section at the sink entrance is higher than that of other sites, where there are outbreaks of water blooms and potential hazards to human health. The dominant functions of each site include carbon metabolism, TCA cycle, and pyruvate metabolism. In addition, the main virulence factors and antibiotic resistance genes in sediment are Type IV pili (VF0082), LOS (CVF494), MymA operon (CVF649), and macrolide resistance genes macB, tetracyclic tetA (58), and novA. Correlation analysis of environmental factors and microorganisms was also performed, and it was discovered that Thiothrix and Acidovorax had obvious gene expression in the nitrogen metabolism pathway, and the Guixi River Basin had a self-purification capacity. Finally, based on the microecological composition of sediment and physical and chemical characteristics of the water body, the health assessment was carried out, indicating that the main pollution area was Dianjiang Middle School and the watershed near the sewage treatment plant. The findings should theoretically support an in-depth assessment of the water environment's microecological health.

Dexmedetomidine attenuates sleep deprivation-induced inhibition of hippocampal neurogenesis via VEGF-VEGFR2 signaling and inhibits neuroinflammation.

Long periods of sleep deprivation (SD) have serious effects on health. While the α2 adrenoceptor agonist dexmedetomidine (DEX) can improve sleep quality for patients who have insomnia, the effect of DEX on cognition and mechanisms after SD remains elusive. C57BL/6 mice were subjected to 20 h SD daily for seven days. DEX (100 µg/kg) was administered intravenously twice daily (at 1:00 p.m. and 3:00 p.m.) during seven days of SD. We found that systemic administration of DEX attenuated cognitive deficits by performing the Y maze and novel object recognition tests and increased DCX+, SOX2+, Ki67+, and BrdU+NeuN+/NeuN+ cell numbers in the dentate gyrus (DG) region of SD mice by using immunofluorescence, western blotting, and BrdU staining. DEX did not reverse the decrease in DCX+, SOX2+, or Ki67+ cell numbers in SD mice after administration of the α2A-adrenoceptor antagonist BRL-44408. Furthermore, the vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) expression was upregulated in SD+DEX mice compared with SD mice. Luminex analysis showed that the neurogenic effects of DEX were possibly related to the inhibition of neuroinflammation, including IL-1α, IL-2, CCL5, and CXCL1. Our results suggested that DEX alleviated the impaired learning and memory of SD mice potentially by inducing hippocampal neurogenesis via the VEGF-VEGFR2 signaling pathway and by suppressing neuroinflammation, and α2A adrenoceptors are required for the neurogenic effects of DEX after SD. This novel mechanism may add to our knowledge of DEX in the clinical treatment of impaired memory caused by SD.

Macro-analysis of climatic factors for COVID-19 pandemic based on Köppen-Geiger climate classification.

This study integrated dynamic models and statistical methods to design a novel macroanalysis approach to judge the climate impacts. First, the incidence difference across Köppen-Geiger climate regions was used to determine the four risk areas. Then, the effective influence of climate factors was proved according to the non-climate factors' non-difference among the risk areas, multi-source non-major component data assisting the proof. It is found that cold steppe arid climates and wet temperate climates are more likely to transmit SARS-CoV-2 among human beings. Although the results verified that the global optimum temperature was around 10 °C, and the average humidity was 71%, there was evident heterogeneity among different climate risk areas. The first-grade and fourth-grade risk regions in the Northern Hemisphere and fourth-grade risk regions in the Southern Hemisphere are more sensitive to temperature. However, the third-grade risk region in the Southern Hemisphere is more sensitive to relative humidity. The Southern Hemisphere's third-grade and fourth-grade risk regions are more sensitive to precipitation.

IFITM2 Presents Antiviral Response through Enhancing Type I IFN Signaling Pathway.

Interferon (IFN) helps cells fight viral infections by further inducing the expression of many downstream IFN-stimulated genes (ISGs). Human interferon-inducible transmembrane proteins (IFITM) are one of these ISGs. The antiviral function of human IFITM1, IFITM2, and IFITM3 are well known. In this study, we report that IFITM can significantly inhibit EMCV infectivity in HEK293 cells. Overexpression of IFITM proteins could promote IFN-ß production. Meanwhile, IFITMs facilitated type I IFN signaling pathway adaptor MDA5 expression. We detected the binding of IFITM2 to MDA5 in a co-immunoprecipitation assay. It was also found that the ability of IFITM2 to activate IFN-ß was significantly inhibited after interfering with MDA5 expression, suggesting that MDA5 may play an important role in the activation of the IFN-ß signaling pathway by IFITM2. Moreover, the N-terminal domain plays an active role in the antiviral activity and the activation of IFN-ß by IFITM2. These findings suggest that IFITM2 plays a vital role in antiviral signaling transduction. In addition, a positive feed-forward loop between IFITM2 and type I IFN establishes a key role for IFITM2 in enforcing innate immune responses.

Lipid phosphatase SAC1 suppresses hepatitis B virus replication through promoting autophagic degradation of virions.

Phosphatidylinositol lipids play vital roles in lipid signal transduction, membrane recognition, vesicle transport, and viral replication. Previous studies have revealed that SAC1-like phosphatidylinositol phosphatase (SACM1L/SAC1), which uses phosphatidylinositol-4-phosphate (PI4P) as its substrate, greatly affects the replication of certain bacteria and viruses in vitro. However, it remains unclear whether and how SAC1 modulates hepatitis B virus (HBV) replication in vitro and in vivo. In the present study, we observed that SAC1 silencing significantly increased HBV DNA replication, subviral particle (SVP) expression, and secretion of HBV virions, whereas SAC1 overexpression exerted the opposite effects. Moreover, SAC1 overexpression inhibited HBV DNA replication and SVP expression in a hydrodynamic injection-based HBV-persistent replicating mouse model. Mechanistically, SAC1 silencing increased the number of HBV-containing autophagosomes as well as PI4P levels on the autophagosome membrane. Moreover, SAC1 silencing blocked autophagosome-lysosome fusion by inhibiting the interaction between synaptosomal-associated protein 29 and vesicle-associated membrane protein 8. Collectively, our data indicate that SAC1 significantly inhibits HBV replication by promoting the autophagic degradation of HBV virions. Our findings support that SAC1-mediated phospholipid metabolism greatly modulates certain steps of the HBV life-cycle and provide a new theoretical basis for antiviral therapy.

Exploring the Temporal Consistency of Arbitrary Style Transfer: A Channelwise Perspective.

Arbitrary image stylization by neural networks has become a popular topic, and video stylization is attracting more attention as an extension of image stylization. However, when image stylization methods are applied to videos, unsatisfactory results that suffer from severe flickering effects appear. In this article, we conducted a detailed and comprehensive analysis of the cause of such flickering effects. Systematic comparisons among typical neural style transfer approaches show that the feature migration modules for state-of-the-art (SOTA) learning systems are ill-conditioned and could lead to a channelwise misalignment between the input content representations and the generated frames. Unlike traditional methods that relieve the misalignment via additional optical flow constraints or regularization modules, we focus on keeping the temporal consistency by aligning each output frame with the input frame. To this end, we propose a simple yet efficient multichannel correlation network (MCCNet), to ensure that output frames are directly aligned with inputs in the hidden feature space while maintaining the desired style patterns. An inner channel similarity loss is adopted to eliminate side effects caused by the absence of nonlinear operations such as softmax for strict alignment. Furthermore, to improve the performance of MCCNet under complex light conditions, we introduce an illumination loss during training. Qualitative and quantitative evaluations demonstrate that MCCNet performs well in arbitrary video and image style transfer tasks. Code is available at https://github.com/kongxiuxiu/MCCNetV2.

NiOx for interface and work function engineering in carbon-based all-inorganic perovskite solar cells.

Carbon-based all-inorganic perovskite solar cells (C-IPSCs) are stable, upscalable and have low CO2-footprint to fabricate. However, they are inefficient in converting light to electricity due to poor hole extraction at perovskite/carbon interface. Here we enable an efficient hole extraction in C-IPSCs with the aid of inorganic p-type nickel oxide nanoparticles (NiOx-NPs) at the interface and in carbon. By tailoring the work function (WF) of carbon, and reducing the energy-level misalignment at the perovskite/carbon interface, NiOx-NPs enable efficient hole transfer, reduce charge recombination and minimize energy loss. As a result, we report 15.01% and 11.02% efficiencies for CsPbI2Br and CsPbIBr2 C-IPSCs, respectively, with a high open-circuit voltage of ∼1.3 V. Unencapsulated interface-modified CsPbI2Br devices maintained 92.8% of their initial efficiency at ambient conditions after nearly 2,000 h; and 94.6% after heating at 60 °C for 170 h. This strategy to tailor carbon interface with perovskite offers an important knob in improving C-IPSCs performance.

Self-assembly of ß-cyclodextrin-pillar[5]arene molecules into supramolecular nanoassemblies: morphology control by stimulus responsiveness and host-guest interactions.

Macrocyclic molecules have attracted considerable attention as new functional materials owing to their unique pore size structure and excellent host-guest properties. With the development of macrocyclic compounds, the properties of mono-modified macrocyclic materials can be improved by incorporating pillar[n]arene or cyclodextrin derivatives through bridge bonds. Herein, we report the self-assembly of amphiphilic di-macrocyclic host molecules (H1-2) based on ß-cyclodextrin and pillar[5]arene units linked by azophenyl or biphenyl groups. In a H2O/DMSO (19 : 1, v/v) mixed polar solvent, an amphiphile H1 with an azophenyl group self-assembled into unique nanorings and exhibited an obvious photoresponsive colour change. This photochromic behaviour makes H1 suitable for application in carbon paper materials on which arbitrary patterns can be erased and rewritten. The amphiphile H2, with a biphenyl unit, self-assembled into spherical micelles. These differences indicate that various linker units lead to changes in the intermolecular and hydrophilic-hydrophobic interactions. In a CHCl3/DMSO (19 : 1, v/v) mixed low-polarity solvent, the amphiphile H1 self-assembled into fibrous aggregates, whereas the molecule H2 assembled into unique nanoring aggregates. In this CHCl3/DMSO mixed solvent system, small nanosheet aggregates were formed by the addition of a guest molecule (G) composed of tetraphenylethene and hexanenitrile groups. With prolonged aggregation time, the small sheet aggregates further aggregated into cross-linked nanoribbons and eventually formed large nanosheet aggregates. The data reveal that the morphology of H1-2 can be controlled by tuning the intermolecular interactions of the molecules via the formation of host-guest complexes. Moreover, the polyhydroxy cyclodextrin unit on H1-2 can be strongly adsorbed on the stationary phase in column chromatography via multiple hydrogen bonds, and the singly modified pillar[5]arenes can be successfully separated by host-guest interactions.

Inhibition of integrated stress response protects against lipid-induced senescence in hypothalamic neural stem cells in adamantinomatous craniopharyngioma.

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a benign tumor with malignant clinical manifestations. ACP adjacent to the hypothalamus often presents with more severe symptoms and higher incidence of hypothalamic dysfunction. However, the mechanism underlying hypothalamic dysfunction remains unclear. METHODS: Immunostaining was performed to determine the nerve damage to the floor of the third ventricle (3VF) adjacent to ACP and to examine the recruitment and senescence of hypothalamic neural stem cells (htNSCs). The accumulation of lipid droplets (LDs) in htNSCs was evaluated via BODIPY staining, oil red O staining, and transmission electron microscopy. In vitro and in vivo assays were used to evaluate the effect of cystic fluid or oxidized low-density lipoprotein and that of oxytocin (OXT) on htNSC senescence and the hypothalamic function. The protein expression levels were analyzed using western blotting. RESULTS: htNSCs with massive LD accumulation were recruited to the damaged 3VF adjacent to ACP. The LDs in htNSCs induced senescence and reduced neuronal differentiation; however, htNSC senescence was effectively prevented by inhibiting either CD36 or integrated stress response (ISR) signaling. Furthermore, OXT pretreatment reduced lipotoxicity via the inhibition of ISR signaling and the repair of the blood-brain barrier. CONCLUSIONS: Reduced LD aggregation or ISR signaling inhibition prevented senescence in htNSCs and identified molecular pathways and potential therapeutic targets that may improve hypothalamic dysfunction in ACP patients.