STAMENLESS1 activates SUPERWOMAN 1 and FLORAL ORGAN NUMBER 1 to control floral organ identities and meristem fate in rice.

Floral patterns are unique to rice and contribute significantly to its reproductive success. SL1 encodes a C2H2 transcription factor that plays a critical role in flower development in rice, but the molecular mechanism regulated by it remains poorly understood. Here, we describe interactions of the SL1 with floral homeotic genes, SPW1, and DL in specifying floral organ identities and floral meristem fate. First, the sl1 spw1 double mutant exhibited a stamen-to-pistil transition similar to that of sl1, spw1, suggesting that SL1 and SPW1 may located in the same pathway regulating stamen development. Expression analysis revealed that SL1 is located upstream of SPW1 to maintain its high level of expression and that SPW1, in turn, activates the B-class genes OsMADS2 and OsMADS4 to suppress DL expression indirectly. Secondly, sl1 dl displayed a severe loss of floral meristem determinacy and produced amorphous tissues in the third/fourth whorl. Expression analysis revealed that the meristem identity gene OSH1 was ectopically expressed in sl1 dl in the fourth whorl, suggesting that SL1 and DL synergistically terminate the floral meristem fate. Another meristem identity gene, FON1, was significantly decreased in expression in sl1 background mutants, suggesting that SL1 may directly activate its expression to regulate floral meristem fate. Finally, molecular evidence supported the direct genomic binding of SL1 to SPW1 and FON1 and the subsequent activation of their expression. In conclusion, we present a model to illustrate the roles of SL1, SPW1, and DL in floral organ specification and regulation of floral meristem fate in rice.

Highly efficient clustering of long-read transcriptomic data with GeLuster.

MOTIVATION: The advancement of long-read RNA sequencing technologies leads to a bright future for transcriptome analysis, in which clustering long reads according to their gene family of origin is of great importance. However, existing de novo clustering algorithms require plenty of computing resources. RESULTS: We developed a new algorithm GeLuster for clustering long RNA-seq reads. Based on our tests on one simulated dataset and nine real datasets, GeLuster exhibited superior performance. On the tested Nanopore datasets it ran 2.9-17.5 times as fast as the second-fastest method with less than one-seventh of memory consumption, while achieving higher clustering accuracy. And on the PacBio data, GeLuster also had a similar performance. It sets the stage for large-scale transcriptome study in future. AVAILABILITY AND IMPLEMENTATION: GeLuster is freely available at https://github.com/yutingsdu/GeLuster.

Rationally Designed Dual Base Pair Mismatch Enables Toehold-Mediated Strand Displacement to Efficiently Recognize Single-Nucleotide Polymorphism without Enzymes.

The efficiency of the enzyme-free toehold-mediated strand displacement (TMSD) technique is often insufficient to detect single-nucleotide polymorphism (SNP) that possesses only single base pair mismatch discrimination. Here, we report a novel dual base pair mismatch strategy enabling TMSD biosensing for SNP detection under enzyme-free conditions when coupled with catalytic hairpin assembly (CHA) and fluorescence resonance energy transfer (FRET). The strategy is based on a competitive strand displacement reaction mechanism, affected by the thermodynamic stability originating from rationally designed dual base pair mismatch, for the specific recognition of mutant-type DNA. In particular, enzyme-free nucleic acid circuits, such as CHA, emerge as a powerful method for signal amplification. Eventually, the signal transduction of this proposed biosensor was determined by FRET between streptavidin-coated 605 nm emission quantum dots (605QDs, donor) and Cy5/biotin hybridization (acceptor, from CHA) when incubated with each other. The proposed biosensor displayed high sensitivity to the mutant target (MT) with a detection concentration down to 4.3 fM and led to high discrimination factors for all types of mismatches in multiple sequence contexts. As such, the application of this proposed biosensor to investigate mechanisms of the competitive strand displacement reaction further illustrates the versatility of our dual base pair mismatch strategy, which can be utilized for the creation of a new class of biosensors.

Reprogrammable Magnetic Soft Actuators with Microfluidic Functional Modules via Pixel-Assembly.

Magnetic soft actuators and robots have attracted considerable attention in biomedical applications due to their speedy response, programmability, and biocompatibility. Despite recent advancements, the fabrication process of magnetic actuators and the reprogramming approach of their magnetization profiles continue to pose challenges. Here, a facile fabrication strategy is reported based on arrangements and distributions of reusable magnetic pixels on silicone substrates, allowing for various magnetic actuators with customizable architectures, arbitrary magnetization profiles, and integration of microfluidic technology. This approach enables intricate configurations with decent deformability and programmability, as well as biomimetic movements involving grasping, swimming, and wriggling in response to magnetic actuation. Moreover, microfluidic functional modules are integrated for various purposes, such as on/off valve control, curvature adjustment, fluid mixing, dynamic microfluidic architecture, and liquid delivery robot. The proposed method fulfills the requirements of low-cost, rapid, and simplified preparation of magnetic actuators, since it eliminates the need to sustain pre-defined deformations during the magnetization process or to employ laser heating or other stimulation for reprogramming the magnetization profile. Consequently, it is envisioned that magnetic actuators fabricated via pixel-assembly will have broad prospects in microfluidics and biomedical applications.

Bisphenol A Analogues Induce Neuroendocrine Disruption via Gut-Brain Regulation in Zebrafish.

There is epidemiological evidence in humans that exposure to endocrine-disrupting chemicals such as bisphenol A (BPA) is tied to abnormal neuroendocrine function with both behavioral and intestinal symptoms. However, the underlying mechanism of this effect, particularly the role of gut-brain regulation, is poorly understood. We exposed zebrafish embryos to a concentration series (including environmentally relevant levels) of BPA and its analogues. The analogue bisphenol G (BPG) yielded the strongest behavioral impact on zebrafish larvae and inhibited the largest number of neurotransmitters, with an effective concentration of 0.5 µg/L, followed by bisphenol AF (BPAF) and BPA. In neurod1:EGFP transgenic zebrafish, BPG and BPAF inhibited the distribution of enteroendocrine cells (EECs), which is associated with decreased neurotransmitters level and behavioral activity. Immune staining of ace-α-tubulin suggested that BPAF inhibited vagal neural development at 50 and 500 µg/L. Single-cell RNA-Seq demonstrated that BPG disrupted the neuroendocrine system by inducing inflammatory responses in intestinal epithelial cells via TNFα-trypsin-EEC signaling. BPAF exposure activated apoptosis and inhibited neural developmental pathways in vagal neurons, consistent with immunofluorescence imaging studies. These findings show that both BPG and BPAF affect the neuroendocrine system through the gut-brain axis but by different mechanisms, revealing new insights into the modes of bisphenol-mediated neuroendocrine disruption.

Atypical absence seizures and gene variants: A gene-based review of etiology, electro-clinical features, and associated epilepsy syndrome.

Atypical absence seizures are generalized non-convulsive seizures that often occur in children with cognitive impairment. They are common in refractory epilepsy and have been recognized as one of the hallmarks of developmental epileptic encephalopathies. Notably, pathogenic variants associated with AAS, such as GABRG2, GABRG3, SLC6A1, CACNB4, SCN8A, and SYNGAP1, are also linked to developmental epileptic encephalopathies. Atypical absences differ from typical absences in that they are frequently drug-resistant and the prognosis is dependent on the etiology or related epileptic syndromes. To improve clinicians' understanding of atypical absences and provide novel perspectives for clinical treatment, we have reviewed the electro-clinical characteristics, etiologies, treatment, and prognosis of atypical absences, with a focus on the etiology of advancements in gene variants, shedding light on potential avenues for improved clinical management.

Evaluating mAbs binding abilities to Omicron subvariant RBDs: implications for selecting effective mAb therapies.

The ongoing evolution of the Omicron lineage of SARS-CoV-2 has led to the emergence of subvariants that pose challenges to antibody neutralization. Understanding the binding dynamics between the receptor-binding domains (RBD) of these subvariants spike and monoclonal antibodies (mAbs) is pivotal for elucidating the mechanisms of immune escape and for advancing the development of therapeutic antibodies. This study focused on the RBD regions of Omicron subvariants BA.2, BA.5, BF.7, and XBB.1.5, employing molecular dynamics simulations to unravel their binding mechanisms with a panel of six mAbs, and subsequently analyzing the origins of immune escape from energetic and structural perspectives. Our results indicated that the antibody LY-COV1404 maintained binding affinities across all studied systems, suggesting the resilience of certain antibodies against variant-induced immune escape, as seen with the mAb 1D1-Fab. The newly identified mAb 002-S21F2 showed a similar efficacy profile to LY-COV1404, though with a slightly reduced binding to BF.7. In parallel, mAb REGN-10933 emerged as a potential therapeutic candidate against BF.7 and XBB.1.5, reflecting the importance of identifying variant-specific antibody interactions, akin to the binding optimization observed in BA.4/5 and XBB.1.5. And key residues that facilitate RBD-mAb binding were identified (T345, L441, K444, V445, and T500), alongside residues that hinder protein-protein interactions (D420, L455, K440, and S446). Particularly noteworthy was the inhibited binding of V445 and R509 with mAbs in the presence of mAb 002-S21F2, suggesting a mechanism for immune escape, especially through the reduction of V445 hydrophobicity. These findings enhance our comprehension of the binding interactions between mAbs and RBDs, contributing to the understanding of immune escape mechanisms. They also lay the groundwork for the design and optimization of antiviral drugs and have significant implications for the development of treatments against current and future coronaviruses.

Experimental and DFT calculation study on the efficient removal of high fluoride wastewater from metallurgical wastewater by kaolinite.

Fluoride pollution and water scarcity are urgent issues. Reducing fluoride concentration in water is crucial. Kaolinite has been used to study adsorption and fluoride removal in water and to characterize material properties. The experimental results showed that the adsorption capacity of kaolinite decreased with increasing pH. The highest adsorption of fluoride occurred at pH 2, with a capacity of 11.1 mg/g. The fluoride removal efficiency remained high after four regeneration cycles. The fitting results with the Freundlich isotherm model and the external diffusion model showed that the non-homogeneous adsorption of kaolinite fit the adsorption behavior better. Finally, the adsorption mechanism was analyzed by FT-IR and XPS. The binding energies of various adsorption sites and the chemical adsorption properties of atomic states were discussed in relation to DFT calculations. The results showed that Al and H sites were the main binding sites, and the bonding stability for different forms of fluoride varies, with the size of Al-F (-7.498 eV) > H-F (-6.04 eV) > H-HF (-3.439 eV) > Al-HF (-3.283 eV). Furthermore, the density of states and Mulliken charge distribution revealed that the 2p orbital of F was found to be active in the adsorption process and was the main orbital for charge transfer.

Germanene saturable absorber for mode-locked operation in an all-fiber laser with multiple dispersion environments.

In this paper, a high-quality germanene-polyvinyl alcohol (PVA) saturable absorber (SA) with a modulation depth of 3.05% and a saturation intensity of 17.95M W/c m 2 was prepared. Stable conventional mode-locking and harmonic mode-locking (HML) were achieved in germanene-based Er-doped fiber lasers (EDFL) using dispersion management techniques. In a cavity with a net dispersion value of -0.22p s 2, the conventional soliton had a center wavelength of 1558.2 nm, a repetition frequency of 19.09 MHz, and a maximum 3 dB spectrum bandwidth of 3.5 nm. The highest repetition frequencies achieved in cavities with net dispersion values of -2.81p s 2, -1.73p s 2, and -1.09p s 2 were 9.48 MHz, 12.75 MHz, and 12.10 MHz for HML, respectively. Furthermore, the effects of dispersion, power, and the polarization state on HML were systematically investigated. Our research results fully demonstrate the capability of germanene as an optical modulator in generating conventional mode-locked and harmonic mode-locked solitons. This provides meaningful references for promoting its application in ultrafast fiber lasers.

Association between screen time and self-reported balance disorders in middle-aged and older adults: national health and nutrition examination survey.

BACKGROUND: Balance disorders can give rise to sensations of instability, lightheadedness, vertigo, disequilibrium, or syncope, ultimately leading to grave medical, physical, emotional, and societal ramifications. These conditions are highly prevalent among individuals aged 40 and above. Screen time encompasses activities associated with television viewing, video game playing, and non-work-related computer usage. Prolonged screen exposure may engender a spectrum of health issues and even elevate overall mortality rates. However, the available evidence on the potential link between excessive screen time and balance dysfunction remains limited. AIMS: The primary aim of this study was to explore the possible association between prolonged screen exposure and impaired balance function. METHODS: This cross-sectional study utilized data from participants who completed a comprehensive questionnaire in the NHANES database between 1999 and 2002, all of whom were aged over 40 and under 85 years. Participants' screen time was categorized into two groups (< 4 h/d and ≥4 h/d) for subsequent data analysis. Logistic regression, combined with propensity score matching (PSM), was employed to investigate the correlation between screen time and balance disorders. RESULTS: A total of 5176 participants were enrolled in this study, comprising 2,586 men and 2,590 women, with a prevalence rate of balance disorders at 25.7% (1331/5176). The incidence of balance disorders was found to be significantly higher among individuals who spent 4 hours or more per day on screen time compared to those with less screen time (P<0.001). Multivariate logistic analysis conducted on the unmatched cohort revealed a significant association between screen time and balance disorders, with an odds ratio (OR) 1.8 (95%CI 1.57 ∼ 2.05). These findings remained consistent even after adjusting for confounding factors, yielding an OR 1.43 (95%CI 1.24 ∼ 1.66). Moreover, the association persisted when employing various multivariate analyses such as propensity score matching adjusted model, standardized mortality ratio weighting model and pairwise algorithmic model; all resulting in ORs ranging from 1.38 to 1.43 and p-values < 0.001. CONCLUSIONS: After controlling for all covariates, screen time (watching TV, playing video games, and using computers outside of work) was associated with balance dysfunction among middle-aged and older adults. This finding may offer a possible idea for the prevention of dizziness and balance disorders. Nevertheless, additional research is imperative to further validate these results.

Ecological characteristics of sugar beet plant and rhizosphere soil in response to high boron stress: A study of the remediation potential.

High boron (B) stress degrades the soil environment and reduces plant productivity. Sugar beet has a high B demand and potential for remediation of B-toxic soils. However, the mechanism regarding the response of sugar beet plants and rhizosphere soil microbiome to high B stress is not clear. In the potted soil experiment, we set different soil effective B environments (0.5, 5, 10, 30, 50, and 100 mg kg-1) to study the growth status of sugar beets under different B concentrations, as well as the characteristics of soil enzyme activity and microbial community changes. The results showed that sugar beet growth was optimal at 5 mg kg-1 of B. Exceeding this concentration the tolerance index decreased. The injury threshold EC20 was reached at an available B concentration of 35.8 mg kg-1. Under the treatment of 100 mg kg-1, the B accumulation of sugar beet reached 0.22 mg plant-1, and the tolerance index was still higher than 60%, which had not yet reached the lethal concentration of sugar beet. The abundance of Acidobacteriota, Chloroflexi and Patescibacteria increased, which was beneficial to the resistance of sugar beet to high B stress. In summary, under high B stress sugar beet had strong tolerance, enhanced capacity for B uptake and enrichment, and changes in soil microbial community structure. This study provides a theoretical basis for clarifying the mechanism of sugar beet resistance to high B stress and soil remediation.

Loss of microbial functional diversity following Spartina alterniflora invasion reduces the potential of carbon sequestration and nitrogen removal in mangrove sediments-from a gene perspective.

Mangrove ecosystems play an important role in carbon (C) sequestration and nitrogen (N) removal. Although Spartina alterniflora has successively invaded native mangrove habitats during the preceding two decades, the effects of this invasion on the microbial functional potential involved in nutrient cycling remain unclear. In this study, metagenomic sequencing was used to investigate microbial C and N cycling in sediments derived from S. alterniflora and three native mangrove species (Kandelia obovata, Avicennia marina, and Aegiceras corniculatum). Greater differences in functional profiles of C and N cycling-related genes were observed between S. alterniflora and mangrove sediments than between different mangrove sediments. Functional diversity was lower in S. alterniflora sediments than in native mangrove sediments. The growth of Thaumarchaeota and Proteobacteria, was enhanced due to their resilience to diversity loss, while the growth of oligotrophs, such as Chloroflexi and Firmicutes, was inhibited in S. alterniflora sediments. Compared to mangrove sediments, the abundance of genes involved in C fixation and methane production was lower in S. alterniflora sediments. However, S. alterniflora significantly increased the gene abundance of pmo which controlled the oxidation process of CH4 to carbon dioxide. Additionally, genes involved in nitrification were enriched, whereas genes involved in N reduction processes, such as denitrification and dissimilatory nitrate reduction to ammonium, N immobilization, and N mineralization, were depleted in S. alterniflora sediments compared to mangrove sediments. Partial least squares regression models demonstrated that the decrease in soil organic C and increase in pH after S. alterniflora invasion induced the loss of microbial functional diversity, which was the main driver of changes in the abundances of genes involved in C and N cycling. Overall, our findings indicate that S. alterniflora invasion modifies the microbial functional profile of nutrient cycling in native mangrove ecosystems and potentially weakens the capacity of mangroves to sequester carbon and remove nitrogen.

Research on phytotoxicity assessment and photosynthetic characteristics of nicosulfuron residues on Beta vulgaris L.

Nicosulfuron is a common herbicide used to control weeds in maize fields. In northeast China, sugar beet is often grown as a subsequent crop after maize, and its frequently suffers from soil nicosulfuron residue damage, but the related toxicity evaluation and photosynthetic physiological mechanisms are not clear. Therefore, we experimented to evaluate the impacts of nicosulfuron residues on beet growth, photochemical properties, and antioxidant defense system. The results showed that when the nicosulfuron residue content reached 0.3 µg kg-1, it inhibited the growth of sugar beet. When it reached 36 µg kg-1 (GR50), the growth stagnated. Compared to the control group, a nicosulfuron residue of 36 µg kg-1 significantly decreased beet plant height (70.93 %), leaf area (91.85 %), dry weights of shoot (70.34 %) and root (32.70 %). It also notably reduced the potential photochemical activity (Fv/Fo) by 12.41 %, the light energy absorption performance index (PIabs) by 46.09 %, and light energy absorption (ABS/CSm) by 6.56 %. It decreased the capture (TRo/CSm) by 9.30 % and transferred energy (ETo/CSm) by 16.13 % per unit leaf cross-section while increasing the energy flux of heat dissipation (DIo/CSm) by 22.85 %. This ultimately impaired the photochemical capabilities of PSI and PSII, leading to a reduction in photosynthetic performance. Furthermore, nicosulfuron increased malondialdehyde (MDA) content while decreasing superoxide dismutase (SOD) and catalase (CAT) activities. In conclusion, this research clarified the toxicity risk level, lethal dose, and harm mechanism of the herbicide nicosulfuron residue. It provides a theoretical foundation for the rational use of herbicides in agricultural production and sugar beet planting management.

[Diagnostic Value of Ultrasound for Thyroid Nodules With a Spoke-Wheel Blood Flow Pattern].

Objective To explore the diagnostic value of ultrasound for thyroid nodules with a spoke-wheel blood flow pattern.Methods The clinical data of the patients with thyroid nodules presenting a spoke-wheel blood flow pattern examined by ultrasound were collected,and the gray-scale ultrasound features of the nodules were recorded.The diagnostic performance of the Thyroid Imaging Reporting and Data System by American College of Radiology (ACR TI-RADS),Chinese Thyroid Imaging Reporting and Data System (C-TIRADS),and combined specific indicators for the thyroid nodules with a spoke-wheel blood flow pattern was evaluated by comparison with the pathological results,which was regarded as the gold standard.Results A total of 64 patients with thyroid nodules were finally included,including 47 patients with malignant nodules and 17 patients with benign nodules.In addition to the general ultrasound features,central scar mostly appeared in malignant nodules (χ2=5.968,P=0.015),while central coarse calcification was more common in benign nodules (χ2=10.899,P=0.001).After the combination of central scar and central gross calcification,the diagnostic performance of ACR TI-RADS and C-TIRADS was improved (both P<0.001).Conclusions When the thyroid nodule shows a spoke-wheel blood flow pattern,one should be cautious of the possibility of malignancy.Combining central scar and central coarse calcification can improve the accuracy of ultrasonic diagnosis.

Electroluminescence and temperature-dependent time-resolved photoluminescence of monolithically integrated triple-wavelength InGaN-based LED.

Here, we propose a monolithically integrated triple-wavelength InGaN-based LED structure and conduct comprehensive research on its emission dynamics under electrical and optical excitation. Through experimental and numerical analyses, a carrier transport and a recombination process can be manipulated in bandgap-engineered multiple quantum wells (MQWs), thus realizing the manipulation of emission properties. A rational triple-wavelength LED structure is heteroepitaxially grown, which shows excellent color stability versus injected currents. Furthermore, utilizing the temperature-dependent time-resolved photoluminescence (TRPL), triple-wavelength peaks display different TRPL decay behaviors. Especially, an anomalous three-stage decay phenomenon is found for a low-energy peak measured at 10 K, accompanied by a decay profile transition with the increasing temperature. The underlying mechanisms are revealed and correlated with carrier localization, interaction between different QWs, and competition between radiative and nonradiative recombination.

Synthesis of Yellow Fluorescence Carbon Dots for the Applications of Vitamin B12 Detection and Cell Imaging.

In this work, bright yellow fluorescent and multifunctional carbon dots (N-CDs) were prepared by hydrothermal method from O-phenylenediamine and 4-aminobenzoic acid. The fluorescence characterization showed that the N-CDs possessed good optical properties (QY = 32%) and excitation dependent multi-color emission. By exciting with 390 nm, the strong selective interaction of VB12 with N-CDs could result in a sharp decrease in the luminescence of N-CDs at 567 nm. An efficient fluorescence sensor in aqueous solution was constructed which could linearly respond VB12 in wide concentration ranges of 0-90 µM and 140-250 µM. The linear correlation coefficients of N-CDs and VB12 were 0.9950 and 0.9968, respectively, and the detection limit was 0.119 µM. N-CDs were performed for sensitive determination of VB12 in real samples. Moreover, the N-CDs were exploited to image cell. This N-CDs was a sensitive fluorescence probe to monitor VB12 and presented prospective potential in living cells imaging. Schematic diagram of the synthesis process and application research of N-CDs.

Turning Complexity into Simplicity: In Situ Synthesis of High-Performance Si@C Anode in Battery Manufacturing Process by Partially Carbonizing the Slurry of Si Nanoparticles and Dual Polymers.

For Si/C anodes, achieving excellent performance with a simple fabrication process is still an ongoing challenge. Herein, we report a green, facile and scalable approach for the in situ synthesis of Si@C anodes during the electrode manufacturing process by partially carbonizing Si nanoparticles (Si NPs) and dual polymers at a relatively low temperature. Due to the proper mass ratio of the two polymer precursors and proper carbonization temperature, the resultant Si-based anode demonstrates a typical Si@C core-shell structure and has strong mechanical properties with the aid of dual-interfacial bonding between the Si NPs core and carbon shell layer, as well as between the C matrix and the underlying Cu foil. Consequently, the resultant Si@C anode shows a high specific capacity (3458.1 mAh g-1 at 0.2 A g-1), good rate capability (1039 mAh g-1 at 4 A g-1) and excellent cyclability (77.94% of capacity retention at a high current density of 1 A g-1 after 200 cycles). More importantly, the synthesis of the Si@C anode is integrated in situ into the electrode manufacturing process and, thus, significantly decreases the cost of the lithium-ion battery but without sacrificing the electrochemical performance of the Si@C anode. Our results provide a new strategy for designing next-generation, high-capacity and cost-effective batteries.

Novel Omicron Variants Enhance Anchored Recognition of TMEM106B: A New Pathway for SARS-CoV-2 Cellular Invasion.

The recent discovery that TMEM106B serves as a receptor mediating ACE2-independent SARS-CoV-2 entry into cells deserves attention, especially in the background of the frequent emergence of mutant strains. Here, the structure-dynamic features of this novel pathway are dissected deeply. Our investigation revealed that the large loop (RBD@471-491) could anchor TMEM106B, which was then firmly locked by another loop (RBD@444-451). The novel and widely disseminated Omicron variants (BA.2.86/EG.5.1) affect the anchoring recognition of proteins, with BA.2.86 being more likely to impact cells with limited or undetectable ACE2 expression. The large loop of the EG.5.1 variant captures TMEM106B poorly due to impaired electrostatic complementarity. Furthermore, we emphasize that antibody design against these two loops could enhance the protection of ACE2 low-expressing cells according to the alanine scanning mutagenesis of multiple antibodies. We hope this study will provide a novel perspective for the prevention and treatment against this new viral invasion pathway.

A two dimensional Co(OH)2 catalytic gravity-driven membrane for water purification: a green and facile fabrication strategy and excellent water decontamination performance.

Cobalt-based materials are reported to be the most efficient catalysts in sulfate radical advanced oxidation processes (SR-AOPs). A green and facile method was developed in this work to prepare uniform Co(OH)2 hexagonal nanosheets, which was void of any organic solvents via mere ambient temperature stirring. The obtained nanosheets were assembled into a catalytic gravity-driven membrane, through which the removal efficiency of a typical pharmaceutical contaminant, ranitidine (RNTD), could reach ∼100% within 20 min. Meanwhile, the catalytic membrane also demonstrated effective removal performance towards various pollutants. In order to augment the long-term stability of catalytic membranes, Co(OH)2/rGO composites were fabricated using the same strategy, and a Co(OH)2/rGO catalytic membrane was prepared correspondingly. The Co(OH)2/rGO membrane could maintain a ∼100% removal of RNTD over a constant reaction period lasting for up to 165 hours, which was approximately 11 times that of the sole Co(OH)2 membrane (15 h). Analysis of element chemical states, metal ion concentration in filtrates, and quenching experiments suggested that the combination with rGO could promote the electron transfer to accelerate the Co(II) regeneration, restrain the cobalt dissolution to alleviate the active site loss, and contribute to the production of 1O2via synergistic effects of oxygen-containing groups in rGO. Toxicity assessment was performed on RNTD and its degradation intermediates to confirm the reduction in ecotoxicity of the treated feed. Overall, this work not only offered guidance for the application of nanosheets in AOP membranes, but also had implications for the environmentally-friendly preparation protocol to obtain functional metal hydroxides.

Cancer Mutations Converge on a Collection of Protein Assemblies to Predict Resistance to Replication Stress.

Rapid proliferation is a hallmark of cancer associated with sensitivity to therapeutics that cause DNA replication stress (RS). Many tumors exhibit drug resistance, however, via molecular pathways that are incompletely understood. Here, we develop an ensemble of predictive models that elucidate how cancer mutations impact the response to common RS-inducing (RSi) agents. The models implement recent advances in deep learning to facilitate multidrug prediction and mechanistic interpretation. Initial studies in tumor cells identify 41 molecular assemblies that integrate alterations in hundreds of genes for accurate drug response prediction. These cover roles in transcription, repair, cell-cycle checkpoints, and growth signaling, of which 30 are shown by loss-of-function genetic screens to regulate drug sensitivity or replication restart. The model translates to cisplatin-treated cervical cancer patients, highlighting an RTK-JAK-STAT assembly governing resistance. This study defines a compendium of mechanisms by which mutations affect therapeutic responses, with implications for precision medicine. SIGNIFICANCE: Zhao and colleagues use recent advances in machine learning to study the effects of tumor mutations on the response to common therapeutics that cause RS. The resulting predictive models integrate numerous genetic alterations distributed across a constellation of molecular assemblies, facilitating a quantitative and interpretable assessment of drug response. This article is featured in Selected Articles from This Issue, p. 384.