Suppressing Deep-Level Trap Toward Over 13% Efficient Solution-Processed Kesterite Solar Cell.

Cu2ZnSn (S,Se)4 (CZTSSe), a promising absorption material for thin-film solar cells, still falls short of reaching the balance limit efficiency due to the presence of various defects and high defect concentration in the thin film. During the high-temperature selenization process of CZTSSe, the diffusion of various elements and chemical reactions significantly influence defect formation. In this study, a NaOH-Se intermediate layer introduced at the back interface can optimize Cu2ZnSnS4 (CZTS)precursor films and subsequently adjust the Se and alkali metal content to favor grain growth during selenization. Through this back interface engineering, issues such as non-uniform grain arrangement on the surface, voids in bulk regions, and poor contact at the back interface of absorber layers are effectively addressed. This method not only optimizes morphology but also suppresses deep-level defect formation, thereby promoting carrier transport at both interfaces and bulk regions of the absorber layer. Consequently, CZTSSe devices with a NaOH-Se intermediate layer improved fill factor, open-circuit voltage, and efficiency by 13.3%. This work initiates from precursor thin films via back interface engineering to fabricate high-quality absorber layers while advancing the understanding regarding the role played by intermediate layers at the back interface of kesterite solar cells.

Interaction between HTR2A rs3125 and negative life events in suicide attempts among patients with major depressive disorder: a cross-sectional study.

BACKGROUND: Both genetic and environmental factors play crucial roles in the development of major depressive disorder (MDD) and suicide attempts (SA). However, the interaction between both items remains unknown. This study aims to explore the interactions between the genetic variants of the serotonin 2 A receptor (HTR2A) and the nitric oxide synthase 1 (NOS1) and environmental factors in patients who experience MDD and SA. METHODS: A total of 334 patients with MDD and a history of SA (MDD-SA) were recruited alongside 518 patients with MDD with no history of SA (MDD-NSA), and 716 healthy controls (HC). The demographic data and clinical characteristics were collected. Sequenom mass spectrometry was used to detect eight tag-single nucleotide polymorphisms (tagSNPs) in HTR2A (rs1328683, rs17068986, and rs3125) and NOS1 (rs1123425, rs2682826, rs3741476, rs527590, and rs7959232). Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-environment interactions. RESULTS: Four tagSNPs (rs17068986, rs3125, rs527590, and rs7959232) exhibited significant differences between the three groups. However, these differences were not significant between the MDD-SA and MDD-NSA groups after Bonferroni correction. A logistic regression analysis revealed that negative life events (OR = 1.495, 95%CI: 1.071-2.087, P = 0.018), self-guilt (OR = 2.263, 95%CI: 1.515-3.379, P < 0.001), and negative cognition (OR = 2.252, 95%CI: 1.264-4.013, P = 0.006) were all independently associated with SA in patients with MDD. Furthermore, GMDR analysis indicated a significant interaction between HTR2A rs3125 and negative life events. Negative life events in conjunction with the HTR2A rs3125 CG + GG genotype were associated with a higher SA risk in patients with MDD when compared to the absence of negative life events in conjunction with the CC genotype (OR = 2.547, 95% CI: 1.264-5.131, P = 0.009). CONCLUSION: Several risk factors and a potential interaction between HTR2A rs3125 and negative life events were identified in patients with SA and MDD. The observed interaction likely modulates the risk of MDD and SA, shedding light on the pathogenesis of SA in patients with MDD.

Water saving irrigation mediates bioactive pigments metabolism and storage capacity in tomato fruit.

Tomato fruit consumption is influenced by flavor and nutrient quality. In the present study, we investigate the impact of water saving irrigation (WSI) as a pre-harvest management on flavor and nutrient quality of tomato fruit. Our results demonstrate that WSI-treated tomato fruit exhibited improved sensory scores as assessed by a taste panel, accompanied by elevated levels of SlGLK2 expression, sugars, acids, and carotenoid contents compared to non-treated fruit. Notably, WSI treatment significantly enhanced the development of chloroplast and plastoglobulus in chromoplast, which served as carotenoid storage sites and upregulated the expression of carotenoid biosynthetic genes. Furthermore, integrated transcriptome and metabolome analysis revealed heightened expression of sugar and flavonoid metabolism pathways in WSI-treated tomato fruit. Remarkably, the master regulator SlMYB12 displayed a substantially increased expression due to WSI. These findings suggest that WSI is an effective and sustainable approach to enhance the pigments metabolism and storage capacity as well as the organoleptic characteristics and nutritional value of tomato fruit, offering a win-win solution for both water conservation and quality improvement in agro-food production.

Effects of Cu (II) on the Growth of Chlorella vulgaris and Its Removal Efficiency of Pollutants in Synthetic Piggery Digestate.

C. vulgaris has a positive effect on the removal of nutrients from pig farm biogas slurry. However, swine wastewater often contains heavy metal ions, such as Cu (II), which may have impacts on the nutrient removal performance of C. vulgaris. Additionally, the heavy metal ions in wastewater can be adsorbed by microalgae. In this study, the stress effect of Cu (II) on the growth of Chlorella vulgaris, the Cu (II) removal by microalgae, and the effect of different concentrations of Cu (II) on the nutrient removal efficiency of C. vulgaris in biogas slurries were explored. The results showed that the microalgae biomass of microalgae on the sixth day of the experiment was the highest in the treatment with a Cu (II) concentration of 0.5 mg/L, which was 30.1% higher than that of the 2.5 mg/L group. C. vulgaris had higher removal efficiencies of Cu (II) at a Cu (II) concentration of 0.1~1.5 mg/L. The-OH, C=O, -COOH, and C-O groups on the surface of the algal cells play a significant role in the removal of Cu (II). The removal rates of COD, NH3-N, TN, and TP by C. vulgaris at a Cu (II) concentration of 0.5 mg/L were the highest, which were 89.0%, 53.7%, 69.6%, and 47.3%, respectively.

Sensitizing chemotherapy for glioma with fisetin mediated by a microenvironment-responsive nano-drug delivery system.

Drug resistance has become an obstacle to successful cancer chemotherapies, with therapeutic agents effectively traversing the blood-brain barrier (BBB) remaining a great challenge. A microenvironment responsive and active targeting nanoparticle was constructed to enhance the penetration of drugs, leading to improved therapeutic effects. Dynamic light scattering demonstrated that the prepared nanoparticle had a uniform size. The cRGD modification renders the nanoparticle with active targeting capabilities to traverse the BBB for chemotherapy. The disulfide-bond-containing nanoparticle can be disintegrated in response to a high concentration of endogenous glutathione (GSH) within the tumor microenvironment (TME) for tumor-specific drug release, resulting in more effective accumulation. Notably, the released fisetin further increased the uptake of doxorubicin by glioma cells and exerted synergistic effects to promote apoptosis, induce cellular G2/M cycle arrest, and inhibit cell proliferation and migration in vitro. Moreover, the nanoparticle showed favorable anti-glioma effects in vivo. Our study provides a new strategy to overcome drug resistance by utilizing a natural product to sensitize conventional chemotherapeutics with well-designed targeted nanodelivery systems for cancer treatment.

Dosimetric Effect of Thymus and Thoracic Duct on Radiation-Induced Lymphopenia in Patients With Primary Lung Cancer Who Received Thoracic Radiation.

Purpose: Radiation-induced lymphopenia is a well-recognized factor for tumor control and survival in patients with cancer. This study aimed to determine the role of radiation dose to the thymus and thoracic duct on radiation-induced lymphopenia. Methods and Materials: Patients with primary lung cancer treated with thoracic radiation therapy between May 2015 and February 2020 with whole blood count data were eligible. Clinical characteristics, including age, gender, histology, stage, chemotherapy regimen, radiation dosimetry, and absolute lymphocyte count (ALC) were collected. The thymus and thoracic duct were contoured by one investigator for consistency and checked by one senior physician. The primary endpoint was radiation-induced decrease in lymphocytes, defined as the difference in ALC (DALC) before and after radiation therapy. Results: The data of a total of 116 consecutive patients were retrospectively retrieved. Significant correlations were found between DALC and several clinical factors. These factors include stage, chemotherapy or concurrent chemoradiation, biologically effective dose (BED), mean lung dose, mean body dose, effective dose to immune cells (EDIC), mean thymus dose (MTD), and mean thoracic duct dose (MTDD) (all P < .05). Ridge regression showed that DALC = 0.0063 × BED + 0.0172 × EDIC + 0.0002 × MTD + 0.0147 × MTDD + 0.2510 (overall P = .00025 and F = 5.85). The combination model has the highest area under the curve of 0.77 (P < .001) when fitting the logistic regression model on DALC categorized as binary endpoint. The sensitivity and specificity of the combined model were 89% and 58%, respectively. Conclusions: This study demonstrated for the first time that radiation doses to the thymus and thoracic duct are strongly associated with radiation-induced lymphopenia patients with lung cancer. Further validation studies are needed to implement thymus and thoracic duct as organs at risk.

[Pollution Characteristics and Source Apportionment of VOCs in Urban Areas of Liaocheng in Summer].

Based on the online monitoring data of volatile organic compounds(VOCs) and ozone(O3) in Liaocheng in June 2021, the concentration levels, compositional characteristics, daily variation characteristics, and ozone formation potential(OFP) of VOCs on polluted days and clean days were systematically analyzed. Potential source areas of VOCs were identified by the potential source contribution function(PSCF) and concentration-weighted trajectory(CWT). The sources of VOCs in Liaocheng were analyzed using the characteristic species ratio and positive matrix factorization(PMF). The results showed that the hourly mean values of VOCs concentrations on polluted days and clean days in Liaocheng in June 2021 were(115.38±59.12) µg·m-3 and(88.10±33.04) µg·m-3, respectively, and the concentration levels of VOCs in each category showed that oxygenated volatile organic compounds(OVOCs)>alkanes>halogenated hydrocarbons>aromatic hydrocarbons>alkenes>alkynes>organosulfur. VOCs species with large differences in concentrations between polluted and clean days were among the top ten species of the hourly mean VOCs concentrations. The daily trends of concentrations of total VOCs, alkanes, alkynes, aromatic hydrocarbons, halogenated hydrocarbons, and organosulfur showed that the daytime concentrations were lower than the nighttime concentrations, and the daily changes in OVOCs concentrations showed the characteristics of high in the daytime and low at nighttime. The OFP was 285.29 µg·m-3 on polluted days and 212.00 µg·m-3 on clean days, and OVOCs, alkenes, and aromatic hydrocarbons contributed significantly to ozone formation. The PSCF and CWT results found that the potential source areas of VOCs in Liaocheng were concentrated in the northern and northeastern part of Dongchangfu District and the central and southwestern part of Chiping District. The results of the characteristic species ratio indicated that the VOCs in Liaocheng might have been more from coal combustion, gasoline volatilization, and motor vehicle exhaust. The results of PMF showed that industrial emission sources(30.57%), motor vehicle exhaust and oil and gas volatilization sources(19.44%), combustion sources(17.23%), air aging and secondary generation sources(13.69%), solvent usage sources(12.75%), and natural sources(6.32%) were the main sources of VOCs in Liaocheng.

Nonmonotonic enhancement of diversity-induced resonance in systems of mobile oscillators.

Diversity is omnipresent in natural and synthetic extended systems, the phenomenon of diversity-induced resonance (DIR), wherein a moderate degree of the diversity can provoke an optimal collective response, provides researchers a brand-new strategy to amplify and utilize the weak signal. As yet the relevant advances focus mostly on the ideal situations where the interactions among elements are uncorrelated with the physical proximity of agents. Such a consideration overlooks interactions mediated by the motion of agents in space. Here, we investigate the signal response of an ensemble of spatial mobile heterogeneous bistable oscillators with two canonical interacting modes: dynamic and preset. The oscillators are considered as mass points and perform random walks in a two-dimensional square plane. Under the dynamic scheme, the oscillators can only interact with other oscillators within a fixed vision radius. For the preset circumstance, the interaction among oscillators occurs only when all of them are in a predefined region at the same moment. We find that the DIR can be obtained in both situations. Additionally, the strength of resonance nonmonotonically rises with respect to the increase of moving speed, and the optimal resonance is acquired by an intermediate magnitude of speed. Finally, we propose reduced equations to guarantee the occurrence of such mobility-optimized DIR on the basis of the fast switching approximation theory and also examine the robustness of such phenomenon through the excitable FitzHugh-Nagumo model and a different spatial motion mechanism. Our results reveal for the first time that the DIR can be optimized by the spatial mobility and thus has promising potential application in the communication of mobile agents.

Intercellular competitive growth dynamics with microenvironmental feedback.

Normal life activities between cells rely crucially on the homeostasis of the cellular microenvironment, but aging and cancer will upset this balance. In this paper we introduce the microenvironmental feedback mechanism to the growth dynamics of multicellular organisms, which changes the cellular competitive ability and thereby regulates the growth of multicellular organisms. We show that the presence of microenvironmental feedback can effectively delay aging, but cancer cells may grow uncontrollably due to the emergence of the tumor microenvironment (TME). We study the effect of the fraction of cancer cells relative to that of senescent cells on the feedback rate of the microenvironment on the lifespan of multicellular organisms and find that the average lifespan shortened is close to the data for non-Hodgkin's lymphoma in Canada from 1980 to 2015. We also investigate how the competitive ability of cancer cells affects the lifespan of multicellular organisms and reveal that there is an optimal value of the competitive ability of cancer cells allowing the organism to survive longest. Interestingly, the proposed microenvironmental feedback mechanism can give rise to the phenomenon of Parrondo's paradox: When the competitive ability of cancer cells switches between a too-high and a too-low value, multicellular organisms are able to live longer than in each case individually. Our results may provide helpful clues for targeted therapies aimed at the TME.

Nonlinear Landau-Zener-Stückelberg-Majorana tunneling and interferometry of extended Bose-Hubbard flux ladders.

The nonlinear Landau-Zener-Stückelberg-Majorana (LZSM) tunneling dynamics and interferometry of an extended Bose-Hubbard flux ladder are studied. Based on the mean-field theory, the dispersion relation of the system is given, and it is found that loop structures periodically appear in the band structure and the nonlinear LZSM interference occurs naturally without Floquet engineering, which can be effectively modulated by atomic interactions. The nonlinear energy bands and the unique chirality feature of the flux ladder system can be identified through the dynamics of nonlinear Landau-Zener tunneling. Remarkably, the critical position of the noise in the interference pattern can be employed to identify the loop structure in the energy band, establishing an effective link between the nonlinear loop structure and LZSM interferometry. The position, intensity, symmetry, and width of interference patterns strongly depend on the magnetic field, atomic interactions, rung-to-leg coupling ratio, and energy bias, which provides an effective way to measure these parameters using the nonlinear LZSM interferometry. This paper further expands the dynamics of flux ladder systems to complex interaction regions and has potential applications in the precise measurement of related nonlinear systems.

Electrolytic Characteristics of Microhole Array Manufacturing Using Polyacrylamide Electrolyte in 304 Stainless Steel.

Because of the ease with which oxide films form on its surfaces, stainless steel has strong corrosion resistance and excellent processing performance. Electrochemical machining (ECM) is a flexible process that can create microstructures on stainless steel (SS304); however, with traditional masked ECM, the efficiency and accuracy of microstructure machining are low. Proposed here is the use of a non-Newtonian fluid [polyacrylamide (PAM)] as the electrolyte. To date, there have been few papers on the electrochemical dissolution behavior of stainless-steel micromachining with a non-Newtonian fluid as the electrolyte. The aims of the study reported here were to investigate the electrochemical properties of SS304 with PAM and PAM-NaOH as electrolytes, and to explain their electrochemical corrosion mechanisms. The effects of different electrolytes were compared, and the polarization curves of SS304 in PAM and PAM-NaOH electrolyte solutions with different components were analyzed and compared with that in NaNO3 electrolyte. Then, the effects of the main processing parameters (pulse voltage, frequency, and duty ratio) on the machining performance were investigated in detail. A microhole array was obtained with a good quality comprising an average diameter of 330.11 µm, an average depth of 16.13 µm, and a depth-to-diameter ratio of 0.048. Using PAM to process microstructures on stainless-steel surfaces was shown to be feasible, and experiments indicated that the mixed electrolyte (PAM-NaOH) had not only the physical characteristics of a non-Newtonian fluid but also the advantages of a traditional electrolyte to dissolve processing products, and it effectively improved the processing accuracy of masked ECM for SS304.

Mitigating the impact of bisphenol A exposure on mortality: Is diet the key? A cohort study based on NHANES.

Bisphenol A (BPA) is a widespread environmental pollutant linked to detrimental effects on human health and reduced life expectancy following chronic exposure. This prospective cohort study aimed to examine the association between BPA exposure and mortality in American adults and to explore the potential mitigating effects of dietary quality on BPA-related mortality. This study utilized data from 8761 American adults in the 2003-2016 National Health and Nutrition Examination Survey (NHANES). Urinary BPA levels were employed to assess BPA exposure, and dietary quality was evaluated using the Healthy Eating Index-2015 (HEI-2015). All-cause, cardiovascular disease (CVD), and cancer mortality statuses were determined until December 31, 2019, resulting in a cumulative follow-up of 80,564 person-years. The results showed that the highest tertile of urinary BPA levels corresponded to a 36% increase in all-cause mortality and a 62% increase in CVD mortality compared to the lowest tertile. In contrast, the highest tertile of HEI-2015 scores was associated with a 29% reduction in all-cause mortality relative to the lowest tertile. Although no significant interaction was found between HEI-2015 scores and urinary BPA levels concerning mortality, the association between HEI-2015 scores and both all-cause and CVD mortality was statistically significant at low urinary BPA levels. Continuous monitoring of BPA exposure is crucial for evaluating its long-term adverse health effects. Improving dietary quality can lower all-cause mortality and decrease the risk of all-cause and CVD mortality at low BPA exposure levels. However, due to the limited protective effect of dietary quality against BPA exposure, minimizing BPA exposure remains a vital goal.

Recent progress in the effect of ferroptosis of HSCs on the development of liver fibrosis.

Fibrosis is a common pathological process that must take place for multiple chronic liver diseases to develop into cirrhosis and liver cancer. Liver fibrosis (LF) is regulated by various cytokines and signaling pathways in its occurrence and development. Ferroptosis is an important mode of cell death caused by iron-dependent oxidative damage and is regulated by iron metabolism and lipid peroxidation signaling pathways. In recent years, numerous studies have shown that ferroptosis is closely related to LF. As the main material secreted by the extracellular matrix, hepatic stellate cells (HSCs) are a general concern in the development of LF. Therefore, targeting HSC ferroptosis against LF is crucial. This review describes the current status of treating LF by inducing HSC ferroptosis that would aid studies in better understanding the current knowledge on ferroptosis in HSCs and the future research direction in this field.

The nonautophagic functions of autophagy-related proteins.

ABBREVIATIONS: ATG: autophagy related; BECN1: beclin 1; cAMP: cyclic adenosine monophosphate; dsDNA: double-stranded DNA; EMT: epithelial-mesenchymal transition; IFN: interferon; ISCs: intestinal stem cells; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK/JNK: mitogen-activated protein kinase/c-Jun N-terminal kinases; MTOR: mechanistic target of rapamycin kinase; STING1: stimulator of interferon response cGAMP interactor 1; UVRAG: UV radiation resistance associated; VPS: vacuolar protein sorting.

A sensitive ratiometric fluorescence probe with a large spectral shift for sensing and imaging of palladium.

Palladium (Pd) is an important heavy metal with excellent catalytic properties and widely used in organic chemistry and the pharmaceutical industry. Efficient and convenient analytical techniques for Pd are urgently needed due to the hazardous effects of Pd on the environment and human health. Herein, we have developed five new ratiometric probes for the selective detection of Pd0 based on the Pd-catalyzed Tsuji-Trost reaction. Among them, the F-substituted probe PF-Pd showed the largest spectral shift (148 nm) and the most sensitive response (detection limit 2.11 nM). PF-Pd was employed to determine Pd0 in tap water or lake water samples, which presented satisfactory accuracy and precision. In addition, profiting from its distinct colorimetric response, visual detection of Pd0 was performed on PF-Pd loaded test strips or in field soil samples. Furthermore, fluorescence imaging of living 4T1 cells demonstrated that PF-Pd is suitable for imaging of intracellular Pd0. The good analytical performance of PF-Pd may enable it to be widely used in the convenient, rapid, sensitive and selective detection of Pd0 in environmental or biological analysis.

The brassinosteroid signaling component SlBZR1 promotes tomato fruit ripening and carotenoid accumulation.

The plant hormone ethylene is essential for climacteric fruit ripening, although it is unclear how other phytohormones and their interactions with ethylene might affect fruit ripening. Here, we explored how brassinosteroids (BRs) regulate fruit ripening in tomato (Solanum lycopersicum) and how they interact with ethylene. Exogenous BR treatment and increased endogenous BR contents in tomato plants overexpressing the BR biosynthetic gene SlCYP90B3 promoted ethylene production and fruit ripening. Genetic analysis indicated that the BR signaling regulators Brassinazole-resistant1 (SlBZR1) and BRI1-EMS-suppressor1 (SlBES1) act redundantly in fruit softening. Knocking out SlBZR1 inhibited ripening through transcriptome reprogramming at the onset of ripening. Combined transcriptome deep sequencing and chromatin immunoprecipitation followed by sequencing identified 73 SlBZR1-repressed targets and 203 SlBZR1-induced targets involving major ripening-related genes, suggesting that SlBZR1 positively regulates tomato fruit ripening. SlBZR1 directly targeted several ethylene and carotenoid biosynthetic genes to contribute to the ethylene burst and carotenoid accumulation to ensure normal ripening and quality formation. Furthermore, knock-out of Brassinosteroid-insensitive2 (SlBIN2), a negative regulator of BR signaling upstream of SlBZR1, promoted fruit ripening and carotenoid accumulation. Taken together, our results highlight the role of SlBZR1 as a master regulator of tomato fruit ripening with potential for tomato quality improvement and carotenoid biofortification.

Rapid Start-Up Characteristics of Anammox under Different Inoculation Conditions.

The long multiplication time and extremely demanding enrichment environment requirements of Anammox bacteria (AAOB) have led to difficult reactor start-ups and hindered its practical dissemination. Few feasibility studies have been reported on the recovery of AAOB activity initiation after inlet substrate disconnection caused by an unfavorable condition, and few factors, such as indicators of the recovery process, have been explored. Therefore, in this experiment, two modified expanded granular sludge bed reactors (EGSB) were inoculated with 1.5 L anaerobic granular sludge (AGS) + 1 L Anammox sludge (AMS) (R1) and 2.5 L anaerobic granular sludge (AGS) (R2), respectively. After a long-term (140 days) starvation shock at a high temperature (38 °C), the bacteria population activity recovery experiments were conducted. After 160 days, both reactors were successfully started up, and the total nitrogen removal rates exceeded 87%. Due to the experimental period, the total nitrogen removal rate of R2 was slightly higher than that of R1 in the final stage. However, it is undeniable that R2 had a relatively long activity delay during startup, while R1 had no significant activity delay during startup. The sludge obtained from R1 had a higher specific anammox activity (SAA). Analysis of the extracellular polymer substances (EPS) results showed that the extracellular polymer content in R1 was higher than that in R2 throughout the recovery process, indicating that R1 had higher sludge stability and denitrification performance. Scanning electron microscopy (SEM) analysis showed that more extracellular filamentous bacteria could be seen in the R1 reactor with better morphology of Anammox bacteria. In contrast, the R2 reactor had fewer extracellular hyphae and micropores as a percentage and higher filamentous bacteria content. The results of microbial 16SrDNA analysis showed that R1 used AAOB as inoculum to initiate Anammox, and the reactor was enriched with Anammox bacteria earlier and in much greater abundance than R2. The experimental results indicated that inoculating mixed anaerobic granular sludge and Anammox sludge to initiate an anammox reactor was more effective.

Double resonance induced by group coupling with quenched disorder.

Results show that the astrocytes can not only listen to the talk of large assemble of neurons but also give advice to the conversations and are significant sources of heterogeneous couplings as well. In the present work, we focus on such regulation character of astrocytes and explore the role of heterogeneous couplings among interacted neuron-astrocyte components in a signal response. We consider reduced dynamics in which the listening and advising processes of astrocytes are mapped into the form of group coupling, where the couplings are normally distributed. In both globally coupled overdamped bistable oscillators and an excitable FitzHugh-Nagumo (FHN) neuron model, we numerically and analytically demonstrate that two types of bell-shaped collective response curves can be obtained as the ensemble coupling strength or the heterogeneity of group coupling rise, respectively, which can be seen as a new type of double resonance. Furthermore, through the bifurcation analysis, we verify that these resonant signal responses stem from the competition between dispersion and aggregation induced by heterogeneous group and positive pairwise couplings, respectively. Our results contribute to a better understanding of the signal propagation in coupled systems with quenched disorder.

Targeting RNA G-quadruplex with repurposed drugs blocks SARS-CoV-2 entry.

The rapid emergence of SARS-CoV-2 variants of concern, the complexity of infection, and the functional redundancy of host factors, underscore an urgent need for broad-spectrum antivirals against the continuous COVID-19 pandemic, with drug repurposing as a viable therapeutic strategy. Here we report the potential of RNA G-quadruplex (RG4)-targeting therapeutic strategy for SARS-CoV-2 entry. Combining bioinformatics, biochemical and biophysical approaches, we characterize the existence of RG4s in several SARS-CoV-2 host factors. In silico screening followed by experimental validation identify Topotecan (TPT) and Berbamine (BBM), two clinical approved drugs, as RG4-stabilizing agents with repurposing potential for COVID-19. Both TPT and BBM can reduce the protein level of RG4-containing host factors, including ACE2, AXL, FURIN, and TMPRSS2. Intriguingly, TPT and BBM block SARS-CoV-2 pseudovirus entry into target cells in vitro and murine tissues in vivo. These findings emphasize the significance of RG4 in SARS-CoV-2 pathogenesis and provide a potential broad-spectrum antiviral strategy for COVID-19 prevention and treatment.

Brd4 proteolysis-targeting chimera nanoparticles sensitized colorectal cancer chemotherapy.

Bromodomain-Containing Protein 4 (BRD4) is a member of the BET family of bromodomains, which participates in gene transcription process and is closely related to tumor progression. We observed the up-regulated expression of BRD4 in colorectal cancer (CRC) after doxorubicin (DOX) treatment, which might be a potential mechanism for DOX resistance. This study constructed the tumor-targeting (cyclo (Arg-Gly-Asp-D-Phe-Lys)-poly(ethylene glycol)-poly(ε-caprolactone)) (cRGD-PEG-PCL) copolymer for co-delivery of DOX and BRD4 PROTAC degrader ARV-825 (ARV-DOX/cRGD-P) for CRC treatment. The ARV-DOX/cRGD-P complexes elicited synergistic anti-tumor effect via cell cycle arrest and the increased cell apoptosis, and mechanism studies implicated the regulation of proliferation- and apoptosis-related pathways in vitro. Moreover, the administration of ARV-DOX/cRGD-P significantly improved anti-tumor activity in subcutaneous colorectal tumors and colorectal intraperitoneal disseminated tumor models in mice by promoting tumor apoptosis, suppressing tumor proliferation and angiogenesis. Taken together, these data reveal that ARV-825 can heighten DOX sensitivity in CRC treatment and BRD4 is a potential therapeutic target for DOX-resistant CRC. The ARV-DOX/cRGD-P preparations have outstanding anti-cancer effects and may be used for clinical treatment of colorectal cancer in the future.