CRISPR/Cas Technology: The Unique Synthetic Biology Genome-Editing Tool Shifting the Paradigm in Viral Diagnostics, Defense, and Therapeutics.

The emergence of the COVID-19 pandemic has starkly exposed our significantly limited ability to promptly identify and respond to emergent biological threats. Consequently, there is an urgent need to advance biotechnological methods for addressing both known and unforeseen biological hazards. Recently, the CRISPR/Cas system has revolutionized genetic engineering, enabling precise and efficient synthetic biology applications. Therefore, this review aims to provide a comprehensive introduction to the fundamental principles underlying the CRISPR/Cas system and assess the advantages and limitations of various CRISPR/Cas-based techniques applicable to the detection of, defense against, and treatment of viral infections. These techniques include viral diagnostics, the development of antiviral vaccines, B cell engineering for antibody production, viral activation/interference, and epigenetic modifications. Furthermore, this review delves into the challenges and bioethical considerations associated with use of the CRISPR/Cas system. With the continuous evolution of technology, the CRISPR/Cas system holds considerable promise for addressing both existing and unforeseen biological threats.

Double-Shelled Open Hollow Metal-Organic Frameworks for Efficient Aqueous Zn-Ion Batteries.

Multi-shelled hollow metal-organic frameworks (MH-MOFs) are highly promising as electrode materials due to their impressive surface area and efficient mass transfer capabilities. However, the fabrication of MH-MOFs has remained a formidable challenge. In this study, two types of double-shelled open hollow Prussian blue analogues, one with divalent iron (DHPBA-Fe(II)) and the other with trivalent iron (DHPBA-Fe(III)), through an innovative inner-outer growth strategy are successfully developed. The growth mechanism is found to involve lattice matching growth and ligand exchange processes. Subsequently, DHPBA-Fe(II) and DHPBA-Fe(III) are employed as cathodes in aqueous Zn-ion batteries. Significantly, DHPBA-Fe(II) demonstrated exceptional performance, exhibiting a capacity of 92.5 mAh g-1 at 1 A g-1, and maintaining remarkable stability over an astounding 10 000 cycles. This research is poised to catalyze further exploration into the fabrication techniques of MH-MOFs and offer fresh insights into the intricate interplay between electronic structure and battery performance.

ggmsa: a visual exploration tool for multiple sequence alignment and associated data.

The identification of the conserved and variable regions in the multiple sequence alignment (MSA) is critical to accelerating the process of understanding the function of genes. MSA visualizations allow us to transform sequence features into understandable visual representations. As the sequence-structure-function relationship gains increasing attention in molecular biology studies, the simple display of nucleotide or protein sequence alignment is not satisfied. A more scalable visualization is required to broaden the scope of sequence investigation. Here we present ggmsa, an R package for mining comprehensive sequence features and integrating the associated data of MSA by a variety of display methods. To uncover sequence conservation patterns, variations and recombination at the site level, sequence bundles, sequence logos, stacked sequence alignment and comparative plots are implemented. ggmsa supports integrating the correlation of MSA sequences and their phenotypes, as well as other traits such as ancestral sequences, molecular structures, molecular functions and expression levels. We also design a new visualization method for genome alignments in multiple alignment format to explore the pattern of within and between species variation. Combining these visual representations with prime knowledge, ggmsa assists researchers in discovering MSA and making decisions. The ggmsa package is open-source software released under the Artistic-2.0 license, and it is freely available on Bioconductor (https://bioconductor.org/packages/ggmsa) and Github (https://github.com/YuLab-SMU/ggmsa).

Multi-ecosystem services differently affected by over-canopy and understory nitrogen additions in a typical subtropical forest.

Obtaining a holistic understanding of the impacts of atmospheric nitrogen deposition on multiple ecosystem services of forest is essential for developing comprehensive and sustainable strategies, particularly in heavy N deposition regions such as subtropical China. However, such impacts remain incompletely understood, with most previous studies focus on individual ecosystem function or service via understory N addition experiments. To address this knowledge gap, we quantified the effects of over-canopy and understory N additions on multiple ecosystem services based on a 7-year large-scale field experiment in a typical subtropical forest. Our results showed continued over-canopy N addition with 50 kg ha-1 year-1 over a period of 4-7 years significantly increased plant nutrient retention, but did not affect the services of soil nutrient accumulation, water yield, C sequestration (in plants and soil), or oxygen release. There were trade-offs between the soil and plant on providing the services of nutrient accumulation/retention and C sequestration under over-canopy N addition. However, without uptake and retention of tree canopy, the trade-off between soil and plant were more weaken under the understory N addition with 50 kg ha-1 year-1 , and their relationships were even synergetic under the understory N addition with 25 kg ha-1 year-1 . The results suggest that understory N addition cannot accurately simulate the effects of atmospheric N deposition on multiple services, along with mutual relationships. Interestingly, the services of plant N, P retention, and C sequestration exhibited a synergetic increase under the over-canopy N addition but a decrease under the understory N addition. Our results also found tree layer plays a primary role in providing plant nutrient retention service and is sensitive to atmospheric N deposition. Further studies are needed to investigate the generalized effects of forest canopy processes on alleviating the threaten of global change factors in different forest ecosystems.

Latent tuberculosis infection and infection-associated risk factors for miner workers with silicosis in eastern China.

OBJECTIVES: Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study. METHODS: A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection. RESULTS: The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47-32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20-12.70, P = 0.024). CONCLUSIONS: The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants.

Three-year results from phase I of ZUMA-4: KTE-X19 in pediatric relapsed/refractory acute lymphoblastic leukemia.

Here we present the 3-year results of ZUMA-4, a phase I/II multicenter study evaluating the safety and efficacy of KTEX19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in pediatric/adolescent patients with relapsed/refractory B-cell acute lymphoblastic leukemia. Phase I explored two dose levels and formulations. The primary endpoint was the incidence of dose-limiting toxicities. Thirty-one patients were enrolled; KTE-X19 was administered to 24 patients (median age 13.5 years, range 3-20; median follow-up 36.1 months). No dose-limiting toxicities were observed. All treated patients had grade ≥3 adverse events, commonly hypotension (50%) and anemia (42%). Grade 3 cytokine release syndrome rates were 33% in all treated patients, 75% in patients given the dose of 2×106 CAR T cells/kg, 27% in patients given the dose of 1×106 cells/kg in the 68 mL formulation, and 22% in patients given the dose of 1×106 cells/kg in the 40 mL formulation; the percentages of patients experiencing grade ≥3 neurologic events were 21%, 25%, 27%, and 11% respectively. Overall complete remission rates (including complete remission with incomplete hematologic recovery) were 67% in all treated patients, 75% in patients given 2×106 CAR T cells/kg, 64% in patients given 1×106 cells/kg in the 68 mL formulation, and 67% in patients given 1×106 cells/kg in the 40 mL formulation. Overall minimal residual diseasenegativity rates were 100% among responders; 88% of responders underwent subsequent allogeneic stem-cell transplantation. In the 1×106 (40 mL) group (recommended phase II dose), the median duration of remission censored at allogeneic stem-cell transplantation and median overall survival were not reached. Pediatric/adolescent patients with relapsed/refractory B-cell acute lymphoblastic leukemia achieved high minimal residual disease-negative remission rates with a manageable safety profile after a single dose of KTE-X19. Phase II of the study is ongoing at the dose of 1×106 CAR T cells/kg in the 40 mL formulation. ClinicalTrials.gov: NCT02625480.

Electron transport, ferroelectric, piezoelectric and optical properties of two-dimensional In2Te3: a first-principles study.

Two-dimensional (2D) materials have garnered significant interest in the fields of optoelectronics and electronics due to their unique and diverse properties. In this work, the electron transport, ferroelectric, piezoelectric, and optical properties of 2D In2Te3 were systematically investigated using first-principles based on density functional theory. The analysis of the phonon spectrum and elastic modulus of the Born effective criterion indicates that the structure of the novel 2D In2Te3 is dynamically stable. The calculation results show that 2D In2Te3 exhibits a carrier mobility as high as 3680.99 cm2 V-1 s-1 (y direction), a high in-plane polarization of 2.428 × 10-10 C m-1, and an excellent ferroelectric phase transition barrier (52.847 meV) and piezoelectric properties (e11 = 1.52 × 10-10 C m-1). The higher carrier mobility is attributed to the band degeneracy and small carrier effective mass. In addition, biaxial strain is an effective way to modulate the band gap and optical properties of 2D In2Te3. These properties indicate that 2D In2Te3 is a promising candidate material for flexible electronic devices and ferroelectric photovoltaic devices.

Dual-Atom Catalysts Derived from a Preorganized Covalent Organic Framework for Enhanced Electrochemical Oxygen Reduction.

Dual-atom catalysts (DAC) are deemed as promising electrocatalysts due to the abundant active sites and adjustable electronic structure, but the fabrication of well-defined DAC is still full of challenges. Herein, bonded Fe dual-atom catalysts (Fe2 DAC) with Fe2 N6 C8 O2 configuration were developed through one-step carbonization of a preorganized covalent organic framework with bimetallic Fe chelation sites (Fe2 COF). The transition from Fe2 COF to Fe2 DAC involved the dissociation of the nanoparticles and the capture of atoms by carbon defects. Benefitting from the optimized d-band center and enhanced adsorption of OOH* intermediates, Fe2 DAC exhibited outstanding oxygen reduction activity with a half-wave potential of 0.898 V vs. RHE. This work will guide more fabrication of dual-atom and even cluster catalysts from preorganized COF in the future.

ggtreeExtra: Compact Visualization of Richly Annotated Phylogenetic Data.

We present the ggtreeExtra package for visualizing heterogeneous data with a phylogenetic tree in a circular or rectangular layout (https://www.bioconductor.org/packages/ggtreeExtra). The package supports more data types and visualization methods than other tools. It supports using the grammar of graphics syntax to present data on a tree with richly annotated layers and allows evolutionary statistics inferred by commonly used software to be integrated and visualized with external data. GgtreeExtra is a universal tool for tree data visualization. It extends the applications of the phylogenetic tree in different disciplines by making more domain-specific data to be available to visualize and interpret in the evolutionary context.

A Hexagonal Nut-Like Metal-Organic Framework and Its Conformal Transformation.

Hollow structured metal-organic frameworks (MOFs) and their derivatives are desired in catalysis, energy storage, etc. However, fabrication of novel hollow MOFs and revelation of their formation mechanisms remain challenging. Herein, open hollow 2D MOFs in the form of hexagonal nut are prepared through self-template method, which can be readily scaled up at gram scale in a one-pot preparation. The evolution from the initial superstructure to the final stable MOFs is tracked by wide-angle X-ray scattering, transforming from solid hexagon to open hollow hexagon. More importantly, this protocol can be extended to synthesizing a series of open hollow structured MOFs with sizes ranging from ≈120 to ≈1200 nm. Further, open hollow structured cobalt/N-doped porous carbon composites are realized through conformal transformation of the as-prepared MOFs, which demonstrates promising applications in sustainable energy conversion technologies. This study sheds light on the kinetically controlled synthesis of novel 2D MOFs for their extended utilizations.

Enhanced Interfacial Affinity of the Supercapacitor Electrode with a Hydrogel Electrolyte by a Preadsorbed Polyzwitterion Layer.

Polymer hydrogel-based solid-state supercapacitors exhibit great potential applications in flexible devices. Nevertheless, the poor electrode-electrolyte interfacial properties restrict their advances. Herein, by taking the well-developed polyvinyl alcohol (PVA)/H2SO4 gel electrolyte and the graphene film electrode as the prototype, a very simple strategy is demonstrated to improve the interfacial affinity between the electrode and the hydrogel electrolyte by a preadsorbed highly hydrophilic polyzwitterion layer of poly(propylsulfonate dimethylammonium propylmethacrylamide) (PPDP) on the electrode surface. Electrochemical measurements confirm that the charge-transfer resistance on the interface is effectively reduced after modification with PPDP. Consequently, the obtained areal capacitance experiences a 3-fold increase compared to the unmodified ones. Results from electrochemical quartz crystal microbalance with dissipation demonstrate that more ions can be reversibly transferred on the modified interface during the change-discharge cycles, suggesting that the accessible surface area on the electrode is also increased. The hydrophilic PVA layer shows a similar function but with a much smaller efficiency. The strategy depicted here is highly universalizable and can be generalized to different electrode/electrolyte systems or other electrochemical energy storage devices.

Acetylacetone Interferes with Carbon and Nitrogen Metabolism of Microcystis aeruginosa by Cutting Off the Electron Flow to Ferredoxin.

The regulation of photosynthetic machinery with a nonoxidative approach is a powerful but challenging strategy for the selective inhibition of bloom-forming cyanobacteria. Acetylacetone (AA) was recently found to be a target-selective cyanocide for Microcystis aeruginosa, but the cause and effect in the studied system are still unclear. By recording of the chemical fingerprints of the cells at two treatment intervals (12 and 72 h with 0.1 mM AA) with omics assays, the molecular mechanism of AA in inactivating Microcystis aeruginosa was elucidated. The results clearly reveal the effect of AA on ferredoxin and the consequent effects on the physiological and biochemical processes of Microcystis aeruginosa. In addition to its role as an electron acceptor of photosystem I, ferredoxin plays pivotal roles in the assimilation of nitrogen in cyanobacterial cells. The effect of AA on ferredoxin and on nonheme iron of photosystem II first cut off the photosynthetic electron transfer flow and then interrupted the synthesis of adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide phosphate (NADPH), which ultimately might affect carbon fixation and nitrogen assimilation metabolisms. The results here provide missing pieces in the current knowledge on the selective inhibition of cyanobacteria, which should shed light on the better control of harmful blooms.

Review on the contamination and remediation of polycyclic aromatic hydrocarbons (PAHs) in coastal soil and sediments.

The rapid economic and population growth in coastal areas is causing increasingly serious polycyclic aromatic hydrocarbons (PAHs) pollution in these regions. This review compared the PAHs pollution characteristics of different coastal areas, including industrial zones, commercial ports, touristic cities, aquacultural & agricultural areas, oil & gas exploitation areas and megacities. Currently there are various treatment methods to remediate soils and sediments contaminated with PAHs. However, it is necessary to provide a comprehensive overview of all the available remediation technologies up to date, so appropriate technologies can be selected to remediate PAHs pollution. In view of that, we analyzed the characteristics of the remediation mechanism, summarized the remediation methods for soil or sediments in coastal areas, which were physical repair, chemical oxidation, bioremediation and integrated approaches. Besides, this review also reported the development of new multi-functional green and sustainable systems, namely, micro-nano bubble (MNB), biochar, reversible surfactants and peracetic acid. While physical repair, expensive but efficient, was regarded as a suitable method for the PAHs remediation in coastal areas because of land shortage, integrated approaches would produce better results. The ultimate aim of the review was to ensure the successful restructuring of PAHs contaminated soil and sediments in coastal areas. Due to the environment heterogeneity, PAHs pollution in coastal areas remains as a daunting challenge. Therefore, new and suitable technologies are still needed to address the environmental issue.

Baicalin Alleviate Apoptosis via PKC-MAPK Pathway in Porcine Peritoneal Mesothelial Cells Induced by Glaesserella parasuis.

Glaesserella parasuis (GPS), a causative agent of Glässer's disease, is thought to be the main fatal cause of peritonitis in swine, thus resulting in high mortality and morbidity and significant economic losses to the swine industry. However, the mechanisms of GPS infection-induced apoptosis and possible therapeutic pathway for GPS infection in peritonitis remain unclear. Baicalin has important biological functions during disease treatment, such as antiviral, bacterial inhibition, anti-apoptosis, and anti-inflammatory. However, whether baicalin has anti-apoptotic effects during the process of GPS infection in peritonitis is unclear. In the present study, the anti-apoptotic effect and mechanisms of baicalin in GPS infection-induced apoptosis were investigated in porcine peritoneal mesothelial cells (PPMC). The results showed that baicalin could inhibit the apoptosis rate occurrence of PPMC induced by GPS to various degrees and inhibit the expression of apoptosis-related genes and cleaved caspase-3. Meanwhile, baicalin significantly antagonized the expression of p-JNK, p-p38, and p-ERK induced by GPS in PPMC. These findings for the first time demonstrate that baicalin exerted the effect of antagonizing GPS induced apoptosis in PPMC by inhibiting the activation of the PKC-MAPK pathway and could be a therapeutic option in the management of GPS infection.

Treeio: An R Package for Phylogenetic Tree Input and Output with Richly Annotated and Associated Data.

Phylogenetic trees and data are often stored in incompatible and inconsistent formats. The outputs of software tools that contain trees with analysis findings are often not compatible with each other, making it hard to integrate the results of different analyses in a comparative study. The treeio package is designed to connect phylogenetic tree input and output. It supports extracting phylogenetic trees as well as the outputs of commonly used analytical software. It can link external data to phylogenies and merge tree data obtained from different sources, enabling analyses of phylogeny-associated data from different disciplines in an evolutionary context. Treeio also supports export of a phylogenetic tree with heterogeneous-associated data to a single tree file, including BEAST compatible NEXUS and jtree formats; these facilitate data sharing as well as file format conversion for downstream analysis. The treeio package is designed to work with the tidytree and ggtree packages. Tree data can be processed using the tidy interface with tidytree and visualized by ggtree. The treeio package is released within the Bioconductor and rOpenSci projects. It is available at https://www.bioconductor.org/packages/treeio/.

Efficacy of venetoclax in relapsed chronic lymphocytic leukemia is influenced by disease and response variables.

To define the efficacy of venetoclax with extended follow-up and identify clinical or biological treatment effect modifiers, updated data for previously treated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) enrolled in 4 early-phase trials were pooled. Rates of response, complete remission (CR/CRi), and undetectable minimal residual disease (U-MRD) were analyzed for all patients (n = 436) and for those patients who were planned to receive 400 mg/day monotherapy (n = 347). Univariate and multiple regression analyses were performed to identify the pretreatment factors associated with response rates and duration of response (DoR). Objective responses were documented in 75% of all patients, including 22% CR/CRi. Overall, 27% and 16% of the patients achieved U-MRD in blood and marrow, respectively. Estimated median progression-free survival (PFS), DoR, and time to progression were 30.2, 38.4, and 36.9 months, respectively. Similar efficacy outcomes were observed within the 400 mg/day monotherapy subset. For those who achieved CR/CRi, the 3-year PFS estimate was 83%. DoR was superior for patients achieving CR/CRi or U-MRD in landmark analyses. In multiple regression analyses, bulky lymphadenopathy (≥5 cm) and refractoriness to B-cell receptor inhibitor (BCRi) therapy were significantly associated with lower CR rate and shorter DoR. Fewer prior therapies were associated with higher CR rate, but not DoR. Chromosome 17p deletion and/or TP53 mutation and NOTCH1 mutation were consistently associated with shorter DoR, but not probability of response. Thus, both pretreatment factors and depth of response correlated with DoR with venetoclax. Patients without bulky lymphadenopathy, BCRi-refractory CLL, or an adverse mutation profile had the most durable benefit.

Regulation of Photosynthesis in Bloom-Forming Cyanobacteria with the Simplest ß-Diketone.

Selective inhibition of photosynthesis is a fundamental strategy to solve the global challenge caused by harmful cyanobacterial blooms. However, there is a lack of specificity of the currently used cyanocides, because most of them act on cyanobacteria by generating nontargeted oxidative stress. Here, for the first time, we find that the simplest ß-diketone, acetylacetone, is a promising specific cyanocide, which acts on Microcystis aeruginosa through targeted binding on bound iron species in the photosynthetic electron transport chain, rather than by oxidizing the components of the photosynthetic apparatus. The targeted binding approach outperforms the general oxidation mechanism in terms of specificity and eco-safety. Given the essential role of photosynthesis in both natural and artificial systems, this finding not only provides a unique solution for the selective control of cyanobacteria but also sheds new light on the ways to modulate photosynthesis.

Enhancement of sludge electro-dewatering by anthracite powder modification.

Electro-dewatering of sludge has received considerable attention due to its low energy consumption for sludge deep-dewatering. However, prior studies have shown the resistance of dried sludge near anode significantly hinders electro-dewatering. The dewatering performance may be improved by reducing the resistance with the addition of conductive material into sludge. We conditioned municipal sludge by anthracite powder, an inexpensive product, to increase solid conductivity, followed by electro-dewatering. After running for 20 min under a constant voltage of 30 V, when the anthracite powder mass was 10%-22% of raw sludge dry solids mass (DS), the final dry solids content of the mud cake after dehydration was 6.2%-12.9% higher than that from dehydration of unconditioned sludge. The average filtrate flow rate ranged from 0.0243 to 0.0285 g s-1. The lowest unit energy consumption, 0.19 kW h·kgwater-1, which was 14% lower than that of control, was reached when 18% DS of anthracite was added. Our theoretical analysis indicates that properly increasing solid conductivity of sludge can reduce the adverse effect caused by the high electrical resistance of sludge near anode. The experimental results, along with the theoretical analysis, show that using anthracite powder for sludge modification is an economical approach to improve sludge dewatering rate and reduce energy consumption.

Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy.

B-cell receptor pathway inhibitors (BCRis) have transformed treatment of chronic lymphocytic leukemia (CLL); however, the efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRis is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi before enrollment. Venetoclax was initiated at 20 mg daily, followed by intrapatient ramp-up to 400 mg daily. Primary objectives included efficacy (objective response rate [ORR]) and safety of venetoclax. The study enrolled 36 patients who previously received idelalisib (ORR, 67% [24/36]); 2 patients achieved complete remission, and 1 had complete remission with incomplete bone marrow recovery. Median progression-free survival (PFS) has not yet been reached; estimated 12-month PFS was 79%. The most common adverse events (AEs; all grades) were neutropenia (56%), diarrhea (42%), upper respiratory tract infection (39%), thrombocytopenia (36%), nausea (31%), fatigue (28%), cough (22%), rash (22%), and anemia (22%). Grade 3 or 4 AEs were primarily hematologic (neutropenia [50%], thrombocytopenia [25%], and anemia [17%]). No patients experienced tumor lysis syndrome. Venetoclax demonstrated promising clinical activity and favorable tolerability in patients with CLL whose disease progressed during or after idelalisib therapy. This trial was registered at www.clinicaltrials.gov as #NCT02141282.

Design of photonic crystal nonlinear laser power limiter based on topological edge states and optical Kerr effect.

We propose a novel topological photonic crystal nonlinear laser power limiter based on topological edge states and optical Kerr effect. In the proposed laser power limiter, a one-dimensional photonic crystal in topological edge state allows the relatively weak signal light with a certain wavelength to pass through with high transmission, but blocks most of the intense hostile or accidental laser with the same wavelength due to the change of topological edge state generated from optical Kerr effect. Taking a 1064 nm wavelength as an example, we have designed such a nonlinear laser power limiter corresponding to the wavelength. When the optical power density is low (less than 0.12 MW/cm2), the light transmission can reach 82.54%, and the transmission can be reduced to 1.04% when the optical power density is increased to 11.66 MW/cm2. Therefore, this method provides a new promising approach to realize laser protection at the desired wavelength.