Cholesterol metabolism: physiological versus pathological aspects in intracerebral hemorrhage.

Cholesterol is an important component of plasma membranes and participates in many basic life functions, such as the maintenance of cell membrane stability, the synthesis of steroid hormones, and myelination. Cholesterol plays a key role in the establishment and maintenance of the central nervous system. The brain contains 20% of the whole body's cholesterol, 80% of which is located within myelin. A huge number of processes (e.g., the sterol regulatory element-binding protein pathway and liver X receptor pathway) participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis, intracellular transport, and efflux. Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences. Therefore, we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases. Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype, with high mortality and morbidity. Historical cholesterol levels are associated with the risk of intracerebral hemorrhage. Moreover, secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation, such as neuroinflammation, demyelination, and multiple types of programmed cell death. Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage. In this paper, we review normal cholesterol metabolism in the central nervous system, the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage, and the links between cholesterol metabolism and cell death. We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.

Narcissism, perfectionism, and self-promoting behavior on social networking sites among university students in Pakistan / Narcisismo, perfeccionismo y comportamiento de autopromoción en sitios de redes sociales entre estudiantes universitarios en Pakistán

Existe un debate considerable en la literatura sobre cómo el narcisismo predice diversos comportamientos asociados con la utilidad de los sitios de redes sociales, pero los investigadores han prestado menos atención a explorar los mediadores potenciales de esta relación. Con base en la literatura existente, anticipamos que el narcisismo predice comportamientos de autopromoción en los sitios de redes sociales. El estudio actual también investigó el papel mediador del perfeccionismo multidimensional entre el narcisismo y el comportamiento de autopromoción. Se recopiló un total de 605 cuestionarios completos de estudiantes de universidades de Rawalpindi e Islamabad, Pakistán, mediante un muestreo conveniente. El estudio utilizó el Inventario de Personalidad Narcisista (Ames et al., 2006), un cuestionario de desarrollo propio sobre comportamiento de autopromoción en sitios de redes sociales y la Escala de Perfeccionismo Multidimensional (Hewitt et al., 1991). Los hallazgos indicaron que las mujeres en comparación con los hombres y las solteras en comparación con las casadas obtuvieron puntuaciones más altas en narcisismo. Los niveles educativos más altos se asociaron con tasas más altas de narcisismo. Los resultados también sugieren que el narcisismo se correlaciona con el perfeccionismo orientado a uno mismo y, más significativamente, con el narcisismo orientado a los demás. El perfeccionismo orientado a uno mismo y a los demás medió significativamente la relación entre el narcisismo y el comportamiento de autopromoción en los sitios de redes sociales.(AU)

There is considerable debate in the literature about how narcis-sism predicts various behaviors associated with the utility of social net-working sites, but researchers have paid less attention to exploring the po-tential mediators of this relationship.Based on the existing literature, we anticipated that narcissism predicts self-promoting behaviors on social networking sites. The current study also investigated the mediating role of multidimensional perfectionismbetween narcissism and self-promoting behavior. A total of 605 complete questionnaires weregathered fromstu-dents from universities from Rawalpindi and Islamabad, Pakistan using convenient sampling. The study used Narcissistic Personality Inventory (Ames et al., 2006), self-developed Self-promoting Behavior on social net-working sites questionnaire, and the Multidimensional Perfectionism Scale (Hewitt et al., 1991). Findings indicated that females as compared to males and single as comparedto married individuals scored higher on narcissism. Higher educational levels were associated with higher rates of narcissism. The results also suggestthat narcissism correlated with self-oriented per-fectionism, and more significantlywith others-oriented narcissism. Self-oriented and others-oriented perfectionism significantly mediated the rela-tionship between narcissism and self-promoting behavior on social net-working sites.(AU)

[Establishment of a humanized mouse model of HIV-1 infection and quantification of integrated HIV proviral DNA in vivo].

In recent years, virological, pathological, and immunological studies need to be carried out for the emerging anti-human immunodeficiency virus (HIV) therapies such as gene therapy, broadly neutralizing antibodies, and the derived chimeric antigen receptor (CAR)-T immunotherapy, which necessitates suitable, simple, and inexpensive small-animal models and methods for accurate quantification of the viral genome in the HIV-1 infected. In our research, the HIV-∆ENV-Jurkat-EGFP-mCherry cell line was engineered through the infection with a dual-labelled HIV pseudovirus. A nested quantitative PCR (nested-qPCR) method with the cellular genome as the integrated standard was established for the quantification of HIV proviral copies. We administered intravenous injections of healthy human peripheral blood mononuclear cell (PBMC) into NOD/Prkdcscid/IL2rgnull (NPG) mice. To verify engraftment kinetics, we analyzed the percentages of hCD45+, hCD3+, hCD4+, and hCD8+ cells in the peripheral blood of hu-PBMC-NPG mice. To evaluate HIV-1 infection in hu-PBMC-NPG mice, we inoculated these mice with HIV NL4-3-NanoLuc by intraperitoneal (IP) injection. We then monitored the luciferase expression by the small animal imaging system and measured the viral load in the spleen by qPCR. The infiltration of human PBMCs in mice was detected 3-5 weeks after intravenous injection, and the percentage of hCD45 in humanized mouse PBMCs were more than 25% five weeks after IP inoculation. The expression of the virus-associated luciferase protein was detected by luciferase imaging 27 days post infection. Moreover, the viral total DNA, RNA, and proviral DNA copies reached 18 000 copies/106 cells, 15 000 copies/µg RNA, and 15 000 copies/106 cells, respectively, in the mouse spleen. Taken together, we reported a convenient method for building a simple humanized mouse model of HuPBMC-NPG/severe combined immunodeficiency (SCID) by intravenous injection with hu-PBMCs without advanced surgical skills and irradiation. Furthermore, we established a convenient method for the efficient determination of proviral DNA to assess HIV replication in vivo, viral reservoir sizes, and efficacy of novel anti-HIV therapies including CAR-T immunotherapy and gene therapy.

[Transperineal versus transrectal ultrasound-guided prostate biopsy in detection of clinically significant and insignificant prostate cancer: A prospective randomized controlled trial].

OBJECTIVE: To compare transperineal prostate biopsy (TPB) with transrectal ultrasound-guided prostate biopsy (TRUSB) in detection of clinically significant prostate cancer (csPCa) and insignificant PCa (insPCa). METHODS: We conducted a prospective randomized clinical study on 279 patients receiving TPB (n = 144) or TRUSB (n = 135) from January 2022 to January 2023, and compared the detection rates of csPCa and insPCa between the two groups. RESULTS: The detection rate of PCa was significantly higher in the TPB than in the TRUSB group (37.50% vs 28.15%, P = 0.026). There were no statistically significant differences between the TPB and TRUSB groups in the detection rates of insPCa (6.94% ï¼»n = 10ï¼½ vs 4.45% ï¼»n = 6ï¼½, P > 0.05) and csPCa (30.56% ï¼»n = 44ï¼½ vs 23.70% ï¼»n = 32ï¼½, P > 0.05), nor in the detection rate of csPCa between different groups of age, PSA concentration and prostate volume (P > 0.05). No statistically significant differences were observed between the TPB and TRUSB groups either in the positive rate of biopsy punctures (ï¼»16.44 ± 2.86ï¼½% vs ï¼»12.48 ± 2.39ï¼½%, P > 0.05) or in the biopsy-related complications of urinary retention, urinary tract infection, hematuria and rectal bleeding (P > 0.05). CONCLUSION: TPB is more effective than TRUSB in detection of PCa, but there is no statistically significant difference between the two approaches in the detection rates of csPCa and insPCa.

Jujuboside A through YY1/CYP2E1 signaling alleviated type 2 diabetes-associated fatty liver disease by ameliorating hepatic lipid accumulation, inflammation, and oxidative stress.

Non-alcoholic fatty liver disease (NAFLD) was a chronic complication of type 2 diabetes mellitus (T2DM), and this comorbid disease lacked therapeutic drugs. Semen Ziziphi Spinosae (SZS) was the seed of Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow, and it could alleviate the symptoms of T2DM patients. As a triterpene saponin, Jujuboside A (Ju A) was the main active substance isolated from SZS and could improve hyperglycemia of diabetic mice. However, it was still unknown whether Ju A has protective effects on T2DM-associated NAFLD. Our study showed that Ju A attenuated T2DM-associated liver damage by alleviating hepatic lipid accumulation, inflammatory response, and oxidative stress in the liver of db/db mice, and high glucose (HG) and free fatty acid (FFA) co-stimulated human hepatocellular carcinomas (HepG2) cells. Along with the improved hyperglycemia and liver injury, Ju A restrained Yin Yang 1 (YY1)/cytochrome P450 2E1 (CYP2E1) signaling in vivo and in vitro. YY1 overexpression intercepted the protective effects of Ju A on T2DM-induced liver injury via promoting hepatic lipid accumulation, inflammatory response, and oxidative stress. While, the blocking effect of YY1 overexpression on Ju A's hepatoprotective effect was counteracted by further treatment of CYP2E1 specific inhibitor diethyldithiocarbamate (DDC) in vitro. In-depth mechanism research showed that Ju A through YY1/CYP2E1 signaling promoted hepatic fatty acid ß-oxidation, and inhibited inflammatory response and oxidative stress by activating peroxisome proliferator-activated receptor alpha (PPARα), leading to the improvement of T2DM-associated NAFLD. Ju A might be a potential agent in the treatment and health care of T2DM-associated liver disease, especially NAFLD.

Haploidentical Versus Mismatched Unrelated Donor Hematopoietic Cell Transplantation: HLA Factors and Donor Age Considerations.

HLA-mismatched unrelated donors and haploidentical related donors are suitable stem cell sources for hematopoietic cell transplantation (HCT) when patients lack HLA-matched donors. Clinical outcome after mismatched HCT is influenced by HLA factors including the similarity of peptide-binding motifs (PBMs) between the patient and unrelated donor, and of the HLA-B leader in unrelated and haploidentical donors. Whether these factors can aid in the selection between mismatched unrelated and haploidentical donors is not known. To address this question, we investigated outcomes between the two donor types defined by matching for the PBM and leader peptide. We compared PBM-matched (n = 614) and mismatched (n = 958) MMUDs with calcineurin-inhibitor-based prophylaxis to four haploidentical groups that received post-transplant cyclophosphamide (PTCy)-based prophylaxis. The haploidentical groups were B-leader matched/DRB1-mismatched (n = 722), B-leader matched/DRB1-matched (n = 154), B-leader mismatched/DRB1-mismatched (n = 493), and B-leader mismatched/DRB1-matched (n = 63). Multivariate analysis showed that the B-leader matched/DRB1-mismatched haploidentical group had the best overall survival (OS) compared to the PBM-matched MMUD, while other haploidentical groups had comparable OS. The PBM-mismatched MMUD showed the poorest outcomes, similar to the B-leader mismatched/DRB1-matched haploidentical group. Among non-HLA factors, donor age was the most significant predictor of OS. These results suggest that a B-leader matched/DRB1 mismatched haploidentical donor might be the preferred choice among donors of similar age. If such a donor is not available, the youngest donor from either PBM-matched unrelated or other haploidentical groups could be a beneficial choice. These findings need validation with both donor groups receiving PTCy-based graft-versus-host disease prophylaxis.

Shared genetics and causal association between plasma levels of SARS-CoV-2 entry receptor ACE2 and Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the highest risk of COVID-19 infection, hospitalization, and mortality. However, it remains largely unclear about the link between AD and COVID-19 outcomes. ACE2 is an entry receptor for SARS-CoV-2. Circulating ACE2 is a novel biomarker of death and associated with COVID-19 outcomes. METHODS: Here, we explored the shared genetics and causal association between AD and plasma ACE2 levels using large-scale genome-wide association study, gene expression, expression quantitative trait loci, and high-throughput plasma proteomic profiling datasets. RESULTS: We found a significant causal effect of genetically increased circulating ACE2 on increased risk of AD. Cross-trait association analysis identified 19 shared genetic variants, and three variants rs3104412, rs2395166, and rs3135344 at chromosome 6p21.32 were associated with COVID-19 infection, hospitalization, and severity. We mapped 19 variants to 117 genes, which were significantly upregulated in lung, spleen, and small intestine, downregulated in brain tissues, and involved in immune system, immune disease, and infectious disease pathways. The plasma proteins corresponding to LST1, AGER, TNXB, and APOC1 were predominantly associated with COVID-19 infection, ventilation, and death. CONCLUSION: Together, our findings suggest the shared genetics and causal association between AD and plasma ACE2 levels, which may partially explain the link between AD and COVID-19.

Characteristic Extraction and Assessment Methods for Transformers DC Bias Caused by Metro Stray Currents.

Metro stray currents flowing into transformer-neutral points cause the high neutral DC and a transformer to operate in the DC bias state.Because neutral DC caused by stray current varies with time, the neutral DC value cannot be used as the only characteristic indicator to evaluate the DC bias risk level. Thus, unified characteristic extraction and assessment methods are proposed to evaluate the DC bias risk of a transformer caused by stray current, considering the signals of transformer-neutral DC and vibration. In the characteristic extraction method, the primary characteristics are obtained by comparing the magnitude and frequency distributions of transformer-neutral DC and vibration with and without metro stray current invasion. By analyzing the correlation coefficients, the final characteristics are obtained by clustering the primary characteristics with high correlation. Then, the magnitude and frequency characteristics are extracted and used as indicators to evaluate the DC bias risk. Moreover, to avoid the influence of manual experience on indicator weights, the entropy weight method (EWM) is used to establish the assessment model. Finally, the proposed methods are applied based on the neutral DC and vibration test data of a certain transformer. The results show that the characteristic indicators can be extracted, and the transformer DC bias risk can be evaluated by using the proposed methods.

Modification and Synergistic Studies of a Novel Frog Antimicrobial Peptide against Pseudomonas aeruginosa Biofilms.

The overuse of traditional antibiotics has resulted in bacterial resistance and seriously compromised the therapeutic efficacy of traditional antibiotics, making the exploration of new antimicrobials particularly important. Several studies have shown that bioactive peptides have become an important source of new antimicrobial drugs due to their broad-spectrum antibacterial action and lack of susceptibility to resistance. In this study, a novel bioactive peptide Nigrosin-6VL was characterised from the skin secretion of the golden cross band frog, Odorrana andersonii, by using the 'shotgun' cloning strategy. Modifications on the Rana Box of Nigrosin-6VL revealed its critical role in antimicrobial functions. The peptide analogue, 2170-2R, designed to preserve the Rana Box structure while enhancing cationicity, exhibited improved therapeutic efficacy, particularly against Gram-negative bacteria, with a therapeutic value of 45.27. Synergistic studies demonstrated that 2170-2R inherits the synergistic antimicrobial activities of the parent peptides and effectively enhances the antimicrobial capacity of cefepime and gentamicin against both planktonic cells and biofilms. Specifically, 2170-2R can synergise effectively with cefepime and gentamicin against different strains of P. aeruginosa biofilms. Consequently, 2170-2R holds promise as a potent antimicrobial agent developed to combat infections induced by Pseudomonas aeruginosa.

Metabolomics Combined with Physiology and Transcriptomics Reveal the Response of Samsoniella hepiali to Key Metabolic Pathways and Its Degradation Mechanism during Subculture.

During the subculture of filamentous fungi, obvious signs of degradation occur which affect the growth and development of the strain, change the content of metabolites, and interfere with gene expression. However, the specific molecular mechanism of filamentous fungi degradation is still unclear. In this study, a filamentous fungus Samsoniella hepiali was used as the research object, and it was continuously subcultured. The results showed that when the strain was subcultured to the F8 generation, the strain began to show signs of degradation, which was manifested by affecting the apparent morphology, reducing the growth rate and sporulation, and destroying the antioxidant system. Further transcriptome and metabolomics analyses were performed, and the results showed differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) that were mainly enriched in four metabolic pathways: ABC transporters; fatty acid degradation; alanine, aspartate, and glutamate metabolism; and purine metabolism. Many of the metabolites that were significantly enriched in different pathways may mainly be regulated by genes belonging to proteins and enzymes, such as Abcd3, Ass1, and Pgm1. At the same time, in the process of subculture, many genes and metabolites that can induce apoptosis and senescence continue to accumulate, causing cell damage and consuming a lot of energy, which ultimately leads to the inhibition of mycelial growth. In summary, this study clarified the response of S. hepiali strains to key metabolic pathways during subculture and some reasons for the degradation of strains.

Bioinspired film-terminated ridges for enhancing friction force on lubricated soft surfaces.

Enhancing friction force in lubricated, compliant contacts is of particular interest due to its wide application in various engineering and biological systems. In this study, we have developed bioinspired surfaces featuring film-terminated ridges, which exhibit a significant increase in lubricated friction force compared to flat samples. We propose that the enhanced sliding friction can be attributed to the energy dissipation at the lubricated interface caused by elastic hysteresis resulting from cyclic terminal film deformation. Furthermore, increasing inter-ridge spacing or reducing terminal film thickness are favorable design criteria for achieving high friction performance. These findings contribute to our understanding of controlling lubricated friction and provide valuable insights into surface design strategies for novel functional devices.

Impact of Race and Ethnicity on Outcomes after Umbilical Cord Blood Transplantation.

BACKGROUND: Umbilical cord blood transplant (UCBT) improves access to transplant for patients lacking a fully matched donor. Previous Center for International Blood and Marrow Transplant Research (CIBMTR) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT. The current study draws on a larger modern cohort and compares outcomes among White, Latinx, Black, and Asian patients. OBJECTIVE: To compare outcomes by social determinants of health. STUDY DESIGN: We designed a retrospective study using CIBMTR data. US patients were between ages 1 and 80; 983 received single and 1529 double UCBT as reported to CIBMTR, following either a myeloablative (N=1752) or reduced intensity conditioning (N=759) for Acute Myeloid Leukemia, Acute Lymphoid Leukemia, or Myelodysplasia. The primary outcome was 2-year OS. Secondary outcomes included disease free survival, transplant related mortality (TRM), acute and chronic graft vs host disease (GVHD), and GVHD free, relapse free survival (GRFS). RESULTS: For 1705 adults, in univariate analysis, 2-year OS was 41.5% (99% CI, 37.6-45.3) for Whites, 36.1% (99% CI, 28.2-44.5) for Latinx, 45.8% (99% CI, 36.7-55.1) for Blacks, and 44.5% (99% CI, 33.6-55.6) for Asians. In multivariate analysis of adults, Latinx patients had inferior OS compared to black patients (p=0.0005, HR 1.45, 99% CI 1.18-1.79). OS improved over time for all racial/ethnic groups. GVHD rates were comparable among the different racial/ethnic groups. In the 807 children, the 2-year OS in univariate analysis was 66.1% (99% CI, 59.7-72.2) for Whites, 57.1% (99%CI, 49-64.9) for Latinx, 46.8% (99%CI, 35.3-58.4) for Blacks, and 53.8% (99%CI, 32.7-74.2) for Asians. In multivariate analysis, no difference in OS was observed among racial/ethnic groups (p = 0.051). Grade III/IV acute GVHD was higher in Blacks compared with Whites (p= 0.0016, HR 2.25, 99% CI 1.36-3.74) and Latinx (p= 0.0016, HR 2.17, 99% CI 1.43-3.30). There was no survival advantage to receiving a UCB unit from a donor of similar race and ethnicity, for any racial/ethnic groups, for both children and adults. Black and Latinx adult patients were more likely to live in areas defined as high poverty. Patients from high poverty level areas had worse OS (p =0.03), due to a higher rate of TRM (p=0.04). Educational level, and type of insurance did not impact overall survival, GVHD, TRM or other transplant outcomes. Children from areas with a higher poverty level had higher TRM, regardless of race and ethnicity (p=0.02). Public health insurance, such as Medicaid, was also associated with a higher TRM (p=0.02). However, poverty did not impact pediatric OS, DFS, or other post-transplant outcomes. CONCLUSIONS: OS for UCBT has improved over time. In adults, OS is comparable among Whites, Blacks, and Asians and lower for Latinx patients. In children, OS is comparable among Whites, Blacks, Latinx, and Asians, but Grade III/IV acute GVHD was higher in Black patients. There was no survival benefit to matching UCB unit and patient by race and ethnicity for adults and children.

Efficient Dlx2-mediated astrocyte-to-neuron conversion and inhibition of neuroinflammation by NeuroD1.

In vivo astrocyte-to-neuron (AtN) conversion induced by overexpression of neural transcriptional factors has great potential for neural regeneration and repair. Here, we demonstrate that a single neural transcriptional factor, Dlx2, converts mouse striatal astrocytes into neurons in a dose-dependent manner. Lineage-tracing studies in Aldh1l1-CreERT2 mice confirm that Dlx2 can convert striatal astrocytes into DARPP32+ and Ctip2+ medium spiny neurons (MSNs). Time-course studies reveal a gradual conversion from astrocytes to neurons in 1 month, with a distinct intermediate state in between astrocytes and neurons. Interestingly, when Dlx2-infected astrocytes start to lose astrocytic markers, the other local astrocytes proliferate to maintain astrocytic levels in the converted areas. Unexpectedly, although Dlx2 efficiently reprograms astrocytes into neurons in the gray matter striatum, it also induces partial reprogramming of astrocytes in the white matter corpus callosum. Such partial reprogramming of white matter astrocytes is associated with neuroinflammation, which can be suppressed by the addition of NeuroD1. Our results highlight the importance of investigating AtN conversion in both the gray matter and white matter to thoroughly evaluate therapeutic potentials. This study also unveils the critical role of anti-inflammation by NeuroD1 during AtN conversion.

Utilizing ultrasound combined with quinoa protein to improve the texture and rheological properties of Chinese style reduced-salt pork meatballs (lion's head).

This study aimed to investigate the effect of ultrasound treatment times (30 min and 60 min) and levels of quinoa protein (QPE) addition (1 % and 2 %) on the quality of Chinese style reduced-salt pork meatballs, commonly known as lion's head. The water-holding capacity (WHC), gel and rheology characteristics, and protein conformation were assessed. The results indicated that extending the ultrasound treatment time and elevating the quinoa protein content caused conspicuous improvements (P<0.05) in the cooking yield, WHC, textural characteristics, color difference, and salt-soluble protein (SSP) solubility of the meatballs. Furthermore, the structural alterations induced by the ultrasound treatment combined with quinoa protein addition included enhancement in ß-sheet, ß-turn, and random coil structure contents, along with a red-shift in the intrinsic fluorescence peak. Additionally, the storage (G') and loss modulus (G'') of the raw meatballs significantly enhanced (P<0.05), indicating a denser gel structure in parallel with the microstructure. In conclusion, the findings demonstrated that ultrasound combined with quinoa protein enhanced the WHC and texture properties of Chinese style reduced-salt pork meatballs by improving SSP solubility.

Direct air capture of CO2 using biochar prepared from sewage sludge: Adsorption capacity and kinetics.

As an emerging carbon-negative emission technology, carbon dioxide (CO2) capture from the air is an essential safeguard for alleviating global warming. Sludge-activated carbon with excellent mesoporous structure is a potential material for CO2 capture. In this paper, the amino modified sewage sludge materials were used to prepare the porous CO2 adsorbent from air. The effect of preparation conditions on the microstructure of sewage sludge-based activated carbon materials was analyzed by microstructural characterization, and the impacts of activator, pyrolysis temperature, and the concentration of modifier on the CO2 adsorption performance of sewage sludge-based activated carbon materials were also systematically investigated. The results show that the pyrolysis temperature, the type of activator and the modifier concentration significantly affect the adsorption performance of sewage sludge-based CO2 adsorption materials. Among them, the sewage sludge-based CO2 adsorption material prepared with solid NaOH as an activator, with an activation temperature of 600 °C and loading concentration of 20 %, exhibited the best performance, that is the CO2 adsorption capacity reached 1.17 mmol/g, and the half time is about four min, which shows better performance, compared with other adsorbents for CO2 capture from air. The research results can reduce CO2 emissions on the one hand, and on the other hand, realize the resourceful utilization of sewage sludge, which sheds light on "treating the wastes with wastes".

Internal Superwettability Inversion of a COF-Encapsulated Melamine Sponge Prepared by a One-Step Synthesis at Room Temperature.

Superwettable materials have been attracting attention due to their unique properties, showing great application prospects in a variety of fields including oil-water separation. Herein, a kind of covalent organic framework (COF)-encapsulated melamine sponge (MS) capable of internal superwettability inversion is prepared by a one-step synthesis at room temperature. COF is produced in situ on the skeleton of MS, which is favorable for practical application, and the prepared COF-encapsulated sponge (MS@COF) exhibits superhydrophobicity (water contact angle of about 157.0°) due to the rough surface provided by the micro/nanostructure of COF. More importantly, MS@COF displays reversibly superhydrophilicity by simple prewetting, achieving superwettability inversion conveniently, unlike the previous switchable materials that rely on external conditions. This facile intrinsic superwettability inversion greatly enriches the application prospects of this kind of smart sponge.

Stabilization of TGF-ß Receptor 1 by a Receptor-Associated Adaptor Dictates Feedback Activation of the TGF-ß Signaling Pathway to Maintain Liver Cancer Stemness and Drug Resistance.

Dysregulation of the transforming growth factor-ß (TGF-ß) signaling pathway regulates cancer stem cells (CSCs) and drug sensitivity, whereas it remains largely unknown how feedback regulatory mechanisms are hijacked to fuel drug-resistant CSCs. Through a genome-wide CRISPR activation screen utilizing stem-like drug-resistant properties as a readout, the TGF-ß receptor-associated binding protein 1 (TGFBRAP1) is identified as a TGF-ß-inducible positive feedback regulator that governs sensitivity to tyrosine kinase inhibitors (TKIs) and promotes liver cancer stemness. By interacting with and stabilizing the TGF-ß receptor type 1 (TGFBR1), TGFBRAP1 plays an important role in potentiating TGF-ß signaling. Mechanistically, TGFBRAP1 competes with E3 ubiquitin ligases Smurf1/2 for binding to TGFΒR1, leading to impaired receptor poly-ubiquitination and proteasomal degradation. Moreover, hyperactive TGF-ß signaling in turn up-regulates TGFBRAP1 expression in drug-resistant CSC-like cells, thereby constituting a previously uncharacterized feedback mechanism to amplify TGF-ß signaling. As such, TGFBRAP1 expression is correlated with TGFΒR1 levels and TGF-ß signaling activity in hepatocellular carcinoma (HCC) tissues, as well as overall survival and disease recurrence in multiple HCC cohorts. Therapeutically, blocking TGFBRAP1-mediated stabilization of TGFBR1 by selective inhibitors alleviates Regorafenib resistance via reducing CSCs. Collectively, targeting feedback machinery of TGF-ß signaling pathway may be an actionable approach to mitigate drug resistance and liver cancer stemness.

A cargo sorting receptor mediates chloroplast protein trafficking through the secretory pathway.

Nucleus-encoded chloroplast proteins can be transported via the secretory pathway. The molecular mechanisms underlying the trafficking of chloroplast proteins between the intracellular compartments are largely unclear, and a cargo sorting receptor has not previously been identified in the secretory pathway. Here we report a cargo sorting receptor that is specifically present in Viridiplantae and mediates the transport of cargo proteins to the chloroplast. Using a forward genetic analysis, we identified a gene encoding a transmembrane protein (MtTP930) in barrel medic (Medicago truncatula). Mutation of MtTP930 resulted in impaired chloroplast function and a dwarf phenotype. MtTP930 is highly expressed in the aerial parts of the plant and is localized to the ER exit sites (ERESs) and Golgi. MtTP930 contains typical cargo sorting receptor motifs, interacts with Sar1, Sec12 and Sec24, and participates in coat protein II (COPII) vesicular transport. Importantly, MtTP930 can recognize the cargo proteins plastidial N-glycosylated nucleotide pyrophosphatase/ phosphodiesterase (MtNPP) and α-carbonic anhydrase (MtCAH) in the ER, and then transport them to the chloroplast via the secretory pathway. Mutation of a homolog of MtTP930 in Arabidopsis (Arabidopsis thaliana) resulted in a similar dwarf phenotype. Furthermore, MtNPP-GFP failed to localize to chloroplasts when transgenically expressed in Attp930 protoplasts, implying that these cargo sorting receptors are conserved in plants. These findings fill a gap in our understanding of the mechanism by which chloroplast proteins are sorted and transported via the secretory pathway.

Unpacking the hazards: An analytic study of injury patterns and risk factors in urban instant delivery.

The rapid growth of urban instant delivery, facilitated by digital platforms and characterized by on-demand, short-term, task-based labor, has raised concerns about safety, particularly with the increasing frequency of instant delivery crashes (IDCs). This study addresses knowledge gaps in understanding injury patterns and risk factors associated with IDCs. Utilizing data extracted from judicial verdicts on IDC disputes in China, encompassing demographic, contextual, crash, and injury information, the research employs ordered logit regression to identify significant factors affecting injury patterns, the number of injuries per person (IPP), and injury severity. Overall, traffic injuries related to instant delivery services have gradually improved since 2020, as evidenced by the severity of individual accidents, the number of injuries, and the economic losses. Analysis of 648 injuries among 448 non-fatal victims reveals a prevalence of lower extremity injuries, followed by external, upper extremity, and head injuries. While the majority of victims suffered a single injury, approximately 22 % experienced major injuries. Female delivery riders exhibited higher injury ratios across various body regions. Rider risk behavior, type of delivery vehicles, and the mode of transport of non-delivery travelers emerged as significant influencers of injury patterns. Notably, functional and physical intersection areas exhibited the highest injury ratios among facility types. Contrary to conventional wisdom, older riders and travelers aged above 50 were associated with higher injury severity, challenging the perception of young age as the primary risk factor. The prominence of lower extremity injuries underscores the necessity for heightened protective measures for delivery riders. Major injuries among victims emphasize potential long-term consequences and associated costs. The significance of gender, age, and risk behavior as determining factors highlights the need for targeted safety interventions. These findings offer crucial insights for stakeholders, guiding the formulation of precise safety measures and informed policy initiatives within the dynamic landscape of instant delivery safety.