Enhancing plant biotechnology by nanoparticle delivery of nucleic acids.

Plant biotechnology plays a crucial role in developing modern agriculture and plant science research. However, the delivery of exogenous genetic material into plants has been a long-standing obstacle. Nanoparticle-based delivery systems are being established to address this limitation and are proving to be a feasible, versatile, and efficient approach to facilitate the internalization of functional RNA and DNA by plants. The nanoparticle-based delivery systems can also be designed for subcellular delivery and controlled release of the biomolecular cargo. In this review, we provide a concise overview of the recent advances in nanocarriers for the delivery of biomolecules into plants, with a specific focus on applications to enhance RNA interference, foreign gene transfer, and genome editing in plants.

Episymbiotic Saccharibacteria TM7x modulates the susceptibility of its host bacteria to phage infection and promotes their coexistence.

Bacteriophages (phages) play critical roles in modulating microbial ecology. Within the human microbiome, the factors influencing the long-term coexistence of phages and bacteria remain poorly investigated. Saccharibacteria (formerly TM7) are ubiquitous members of the human oral microbiome. These ultrasmall bacteria form episymbiotic relationships with their host bacteria and impact their physiology. Here, we showed that during surface-associated growth, a human oral Saccharibacteria isolate (named TM7x) protects its host bacterium, a Schaalia odontolytica strain (named XH001) against lytic phage LC001 predation. RNA-Sequencing analysis identified in XH001 a gene cluster with predicted functions involved in the biogenesis of cell wall polysaccharides (CWP), whose expression is significantly down-regulated when forming a symbiosis with TM7x. Through genetic work, we experimentally demonstrated the impact of the expression of this CWP gene cluster on bacterial-phage interaction by affecting phage binding. In vitro coevolution experiments further showed that the heterogeneous populations of TM7x-associated and TM7x-free XH001, which display differential susceptibility to LC001 predation, promote bacteria and phage coexistence. Our study highlights the tripartite interaction between the bacterium, episymbiont, and phage. More importantly, we present a mechanism, i.e., episymbiont-mediated modulation of gene expression in host bacteria, which impacts their susceptibility to phage predation and contributes to the formation of "source-sink" dynamics between phage and bacteria in biofilm, promoting their long-term coexistence within the human microbiome.

Lysosomal cation channel TRPML1 suppression sensitizes acute myeloid leukemia cells to chemotherapeutics by inhibiting autophagy.

Despite the implementation of novel therapeutic regimens and extensive research efforts, chemoresistance remains a formidable challenge in the treatment of acute myeloid leukemia (AML). Notably, the involvement of lysosomes in chemoresistance has sparked interest in developing lysosome-targeted therapies to sensitize tumor cells to currently approved chemotherapy or as innovative pharmacological approaches. Moreover, as ion channels on the lysosomal membrane are critical regulators of lysosomal function, they present potential as novel targets for enhancing chemosensitivity. Here, we discovered that the expression of a lysosomal cation channel, namely transient receptor potential mucolipin 1 (TRPML1), was elevated in AML cells. Inhibiting TRPML1 individually does not impact the proliferation and apoptosis of AML cells. Importantly, inhibition of TRPML1 demonstrated the potential to modulate the sensitivity of AML cells to chemotherapeutic agents. Exploration of the underlying mechanisms revealed that suppression of TRPML1 impaired autophagy while concurrently increasing the production of reactive oxygen species (ROS) and ROS-mediated lipid peroxidation (Lipid-ROS) in AML cells. Finally, the knockdown of TRPML1 significantly reduced OCI-AML3 tumor growth following chemotherapy in a mouse model of human leukemia. In summary, targeting TRPML1 represents a promising approach for combination therapy aimed at enhancing chemosensitivity in treating AML.

Development of europium(III) complex functionalized silica nanoprobe for luminescence detection of tetracycline.

Increasing awareness of the health and environment impacts of the antibiotics misuse or overuse, such as tetracycline (TC) in treatment or prevention of infections and diseases, has driven the development of robust methods for their detection in biological, environmental and food systems. In this work, we report the development of a new europium(III) complex functionalized silica nanoprobe (SiNPs-Eu3+) for highly sensitive and selective detection of TC residue in aqueous solution and food samples (milk and meat). The nanoprobe is developed by immobilization of Eu3+ ion onto the surface of silica nanoparticles (SiNPs) as the emitter and TC recognition unit. The ß-diketone configuration of TC can further coordinate with Eu3+ steadily on the surface of nanoprobe, facilitating the absorption of light excitation for Eu3+ emitter activation and luminescence "off-on" response. The dose-dependent luminescence enhancement of SiNPs-Eu3+ nanoprobe exhibits good linearities, allowing the quantitative detection of TC. The SiNPs-Eu3+ nanoprobe shows high sensitivity and selectivity for TC detection in buffer solution. Time resolved luminescence analysis enables the elimination of autofluorescence and light scattering for highly sensitive detection of TC in milk and pork mince with high accuracy and precision. The successful development of SiNPs-Eu3+ nanoprobe is anticipated to provide a rapid, economic, and robust approach for TC detection in real world samples.

A WOx/MoOx hybrid oxide based SERS FET and investigation on its tunable SERS performance.

Active control of the surface-enhanced Raman scattering (SERS) enhancement shows great potential for realizing smart detection of different molecules. However, conventional methods usually involve time-consuming structural design or a sophisticated fabrication process. Herein, we reported an electrically tunable field effect transistor (FET) comprising a WOx/MoOx hybrid as the SERS active layer. In the experiment, WOx/MoOx hybrids were first prepared by mixing different molar ratios of WOx and MoOx oxides. Then, R6G molecules were used as Raman reporters, showing that the intensity of the SERS signal observed on the most optimal hybrids (molar ratio = 1 : 3) could be increased by two times as high as that observed on a single WOx or MoOx based substrate, which was ascribed to enhanced charge transfer efficiency by the constructed nano-heterojunction between the WOx and MoOx oxides. Thereafter, a back-gate FET was fabricated on a SiO2/Si substrate, and the most optimal WOx/MoOx hybrid was deposited as the gate channel and the SERS active layer. After that, a series of gate biases (from -15 V to 15 V) were implemented to actively tune the SERS performance of the FET. It is evident that the SERS EF can be further tuned from 2.39 × 107 (-15 V) to 6.55 × 107 (+10 V), which is ∼7.4/4.1 times higher than that observed on the pure WOx device (8.81 × 106) or pure MoOx (1.61 × 107) device, respectively. Finally, the mechanism behind the electrical tuning strategy was investigated. It is revealed that a positive voltage would bend the conduction band down, which increased the electron density near the Fermi level. Consequently, it triggered the resonance charge transfer and significantly improved the SERS performance. In contrast, a negative gate voltage attracted the holes to the Fermi level, which deferred the charge transfer process, and caused the reduction of the SERS enhancement.

Emerging Trends in Teledermatology Research: A Scientometric Analysis from 2002 to 2021.

Background: With advances in technology, teledermatology (TD) research has increased. However, an updated comprehensive quantitative analysis of TD research, especially one that identifies emerging trends of TD research in the coronavirus disease 2019 (COVID-19) era, is lacking. Objective: To conduct a scientometric analysis of TD research documents between 2002 and 2021 and explore the emerging trends. Methods: CiteSpace was used to perform scientometric analysis and yielded visualized network maps with corresponding metric values. Emerging trends were identified mainly through burst detection of keywords/terms, co-cited reference clustering analysis, and structural variability analysis (SVA). Results: A total of 932 documents, containing 27,958 cited references were identified from 2002 to 2021. Most TD research was published in journals from the "Dermatology" and "Health Care Sciences & Services" categories. American, Australian, and European researchers contributed the most research and formed close collaborations. Keywords/terms with strong burst values to date were "primary care," "historical perspective," "emerging technique," "improve access," "mobile teledermoscopy (TDS)," "access," "skin cancer," "telehealth," "recent finding," "artificial intelligence (AI)," "dermatological care," and "dermatological condition." Co-cited reference clustering analysis showed that the recently active cluster labels included "COVID-19 pandemic," "skin cancer," "deep neural network," and "underserved population." The SVA identified two reviews (Tognetti et al. and Mckoy et al.) that may be highly cited in the future. Conclusion: During and after the COVID-19 era, emerging trends in research on TD (especially mobile TDS) may be related to skin cancer and AI as well as further exploration of primary care in underserved areas.

Diborodichloromethane as Versatile Reagent for Chemodivergent Synthesis of gem-Diborylalkanes.

The development of boron reagents is crucial for synthetic chemistry. Herein, we present a scalable and practical synthesis of diborodichloromethane (DBDCM) through the reaction of trichloromethyllithium with bis(pinacolato)diboron (B2 pin2 ). The resulting DBDCM reagent serves as a basic synthetic unit for the construction of various structurally diverse gem-diborylalkanes through controllable C-Cl functionalizations. Moreover, we have developed consecutive tetra-functionalizations of DBDCM for the construction of diverse tertiary and quaternary carbon containing molecules. The use of isotopically enriched 13 C-chloroform and 10 B2 pin2 enables the synthesis of isotopically enriched 13 C-DBDCM and 10 B-DBDCM reagents, which are beneficial for the convenient synthesis of carbon-13 and boron-10 molecules.

Topologically Tunable Conjugated Metal-Organic Frameworks for Modulating Conductivity and Chemiresistive Properties for NH3 Sensing.

Electrically conductive metal-organic frameworks (cMOFs) have garnered significant attention in materials science due to their potential applications in modern electrical devices. However, achieving effective modulation of their conductivity has proven to be a major challenge. In this study, we have successfully prepared cMOFs with high conductivity by incorporating electron-donating fused thiophen rings in the frameworks and extending their π-conjugated systems through ring-closing reactions. The conductivity of cMOFs can be precisely modulated ranging from 10-3 to 102 S m-1 by regulating their dimensions and topologies. Furthermore, leveraging the inherent tunable electrical properties based on topology, we successfully demonstrated the potential of these materials as chemiresistive gas sensors with an outstanding response toward 100 ppm NH3 at room temperature. This work not only provides valuable insights into the design of functional cMOFs with different topologies but also enriches the cMOF family with exceptional conductivity properties.

Longitudinal Serum Proteomics Characterization of CD19-CAR-T Cell Therapy for B-Cell Malignancies.

Chimeric antigen receptor (CAR)-modified T cells have demonstrated remarkable efficacy in treating B-cell leukemia. However, treated patients may potentially develop side effects, such as cytokine release syndrome (CRS), the mechanisms of which remain unclear. Here, we collected 43 serum samples from eight patients with B-cell acute lymphoblastic leukemia (B-ALL) before and five time points after CD19-specific CAR-T cell treatment. Using TMTpro 16-plex-based quantitative proteomics, we quantified 1151 proteins and profiled the longitudinal proteomes analysis of each patient. Seven days after therapy, we found the most dysregulated inflammatory proteins. Lipid metabolism proteins, including APOA1, decreased after therapy, reached their minimum after 7 days, and then gradually recovered. Hence, APOA1 has been selected as a potential biomarker of the CRS disease progression. Furthermore, we identified CD163 as a potential biomarker of CRS severity. These two biomarkers were successfully validated using targeted proteomics in an independent cohort. Our study provides new insights into CAR-T cell therapy-induced CRS. The biomarkers we identified may help develop targeted drugs and monitoring strategies.

Clay nanoparticles efficiently deliver small interfering RNA to intact plant leaf cells.

RNA interference is triggered in plants by the exogenous application of double-stranded RNA or small interfering RNA (siRNA) to silence the expression of target genes. This approach can potentially provide insights into metabolic pathways and gene function and afford plant protection against viruses and other plant pathogens. However, the effective delivery of biomolecules such as siRNA into plant cells is difficult because of the unique barrier imposed by the plant cell wall. Here, we demonstrate that 40-nm layered double hydroxide (LDH) nanoparticles are rapidly taken up by intact Nicotiana benthamiana leaf cells and by chloroplasts, following their application via infiltration. We also describe the distribution of infiltrated LDH nanoparticles in leaves and demonstrate their translocation through the apoplast and vasculature system. Furthermore, we show that 40-nm LDH nanoparticles can greatly enhance the internalization of nucleic acids by N. benthamiana leaf cells to facilitate siRNA-mediated downregulation of targeted transgene mRNA by >70% within 1 day of exogenous application. Together, our results show that 40-nm LDH nanoparticle is an effective platform for delivery of siRNA into intact plant leaf cells.

Clinical Report of a Rare Mucinous Staphylococcus Aureus Infection.

BACKGROUND: Staphylococcus aureus is the most common pathogen in suppurative infection, which can cause local suppurative infection, pneumonia, etc. A case of double renal calculi complicated with chronic renal insufficiency and mucinous Staphylococcus aureus infection was analyzed and discussed. METHODS: Bacterial culture, identification, and next-generation sequencing. RESULTS: The mucous colony was identified as Staphylococcus aureus, and the condition improved after symptomatic treatment. CONCLUSIONS: Mucinous Staphylococcus is a rare clinical microorganism, which needs to be verified by experiments to avoid false negative results. Genetic sequencing is used to identify strains if necessary.

Levofloxacin-induced acute rhabdomyolysis: A case report.

Quinolones can cause rhabdomyolysis, but rhabdomyolysis secondary to quinolone use is uncommon, and few reports associate rhabdomyolysis with levofloxacin use. We report a case of acute rhabdomyolysis associated with levofloxacin use. A 58-year-old Chinese woman developed myalgia and difficulty walking ~ 4 days after taking levofloxacin for a respiratory infection. Blood biochemistry revealed elevated peripheral creatine kinase and liver enzyme levels, but the patient did not develop an acute kidney injury. Her symptoms resolved after discontinuation of levofloxacin. This case report highlights the need for monitoring of blood biochemistry in patients taking levofloxacin to enable early diagnosis and treatment of potentially life-threatening myositis.

Guidelines, Consensus Statements, and Standards for the Use of Artificial Intelligence in Medicine: Systematic Review.

BACKGROUND: The application of artificial intelligence (AI) in the delivery of health care is a promising area, and guidelines, consensus statements, and standards on AI regarding various topics have been developed. OBJECTIVE: We performed this study to assess the quality of guidelines, consensus statements, and standards in the field of AI for medicine and to provide a foundation for recommendations about the future development of AI guidelines. METHODS: We searched 7 electronic databases from database establishment to April 6, 2022, and screened articles involving AI guidelines, consensus statements, and standards for eligibility. The AGREE II (Appraisal of Guidelines for Research & Evaluation II) and RIGHT (Reporting Items for Practice Guidelines in Healthcare) tools were used to assess the methodological and reporting quality of the included articles. RESULTS: This systematic review included 19 guideline articles, 14 consensus statement articles, and 3 standard articles published between 2019 and 2022. Their content involved disease screening, diagnosis, and treatment; AI intervention trial reporting; AI imaging development and collaboration; AI data application; and AI ethics governance and applications. Our quality assessment revealed that the average overall AGREE II score was 4.0 (range 2.2-5.5; 7-point Likert scale) and the mean overall reporting rate of the RIGHT tool was 49.4% (range 25.7%-77.1%). CONCLUSIONS: The results indicated important differences in the quality of different AI guidelines, consensus statements, and standards. We made recommendations for improving their methodological and reporting quality. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews (CRD42022321360); https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=321360.

Correction: Guidelines, Consensus Statements, and Standards for the Use of Artificial Intelligence in Medicine: Systematic Review.

[This corrects the article DOI: 10.2196/46089.].

3D Covalent Organic Frameworks with Interpenetrated pcb Topology Based on 8-Connected Cubic Nodes.

The connectivity of building units for 3D covalent organic frameworks (COFs) has long been primarily 4 and 6, which have severely curtailed the structural diversity of 3D COFs. Here we demonstrate the successful design and synthesis of a porphyrin based, 8-connected building block with cubic configuration, which could be further reticulated into an unprecedented interpenetrated pcb topology by imine condensation with linear amine monomers. This study presents the first case of high-connectivity building units bearing 8-connected cubic nodes, thus greatly enriching the topological possibilities of 3D COFs.

Defect-Engineered Co3 O4 @Nitrogen-Deficient Graphitic Carbon Nitride as an Efficient Bifunctional Electrocatalyst for High-Performance Metal-Air Batteries.

The ability to craft high-efficiency and non-precious bifunctional oxygen catalysts opens an enticing avenue for the real-world implementation of metal-air batteries (MABs). Herein, Co3 O4 encapsulated within nitrogen defect-rich g-C3 N4 (denoted Co3 O4 @ND-CN) as a bifunctional oxygen catalyst for MABs is prepared by graphitizing the zeolitic imidazolate framework (ZIF)-67@ND-CN. Co3 O4 @ND-CN possesses superb bifunctional catalytic performance, which facilitates the construction of high-performance MABs. Concretely, the rechargeable zinc-air battery based on Co3 O4 @ND-CN shows a superior round-trip efficiency of ≈60% with long-term durability (over 340 cycles), exceeding the battery with the state-of-the-art noble metals. The corresponding lithium-oxygen battery using Co3 O4 @ND-CN exhibits an excellent maximum discharge/charge capacity (9838.8/9657.6 mAh g-1 ), an impressive discharge/charge overpotential (1.14 V/0.18 V), and outstanding cycling stability. Such compelling electrocatalytic processes and device performances of Co3 O4 @ND-CN originate from concurrent compositional (i.e., defect-engineering) and structural (i.e., wrinkled morphology with abundant porosity) elaboration as well as the well-defined synergy between Co3 O4 and ND-CN, which produce an advantageous surface electronic environment corroborated by theoretical modeling. By extension, a rich diversity of other metal oxides@ND-CN with adjustable defects, architecture, and enhanced activities may be rationally designed and crafted for both scientific research on catalytic properties and technological development in renewable energy conversion and storage systems.

Hepatic NCoR1 deletion exacerbates alcohol-induced liver injury in mice by promoting CCL2-mediated monocyte-derived macrophage infiltration.

Nuclear receptor corepressor 1 (NCoR1) is a corepressor of the epigenetic regulation of gene transcription that has important functions in metabolism and inflammation, but little is known about its role in alcohol-associated liver disease (ALD). In this study, we developed mice with hepatocyte-specific NCoR1 knockout (NCoR1Hep-/-) using the albumin-Cre/LoxP system and investigated the role of NCoR1 in the pathogenesis of ALD and the underlying mechanisms. The traditional alcohol feeding model and NIAAA model of ALD were both established in wild-type and NCoR1Hep-/- mice. We showed that after ALD was established, NCoR1Hep-/- mice had worse liver injury but less steatosis than wild-type mice. We demonstrated that hepatocyte-specific loss of NCoR1 attenuated liver steatosis by promoting fatty acid oxidation by upregulating BMAL1 (a circadian clock component that has been reported to promote peroxisome proliferator activated receptor alpha (PPARα)-mediated fatty ß-oxidation by upregulating de novo lipid synthesis). On the other hand, hepatocyte-specific loss of NCoR1 exacerbated alcohol-induced liver inflammation and oxidative stress by recruiting monocyte-derived macrophages via C-C motif chemokine ligand 2 (CCL2). In the mouse hepatocyte line AML12, NCoR1 knockdown significantly increased ethanol-induced CCL2 release. These results suggest that hepatocyte NCoR1 plays distinct roles in controlling liver inflammation and steatosis, which provides new insights into the development of treatments for steatohepatitis induced by chronic alcohol consumption.

Analysis of microstructure and fatigue of cast versus selective laser-melted dental Co-Cr alloy.

STATEMENT OF PROBLEM: The forces exerted on teeth and prostheses during mastication are repeated and dynamic, resulting in fatigue damage to dental prostheses. Most fractures of dental restorations are fatigue failure. The 4-point bend fatigue behavior of Co-Cr-Mo-W alloys manufactured by investment casting (CAST) and selective laser melting (SLM) has received little attention. PURPOSE: The purpose of this in vitro study was to evaluate the 4-point bend fatigue property of dental Co-Cr alloys and determine the relationship between microstructure and the 4-point bend fatigue property of Co-Cr alloys created by traditional casting and SLM. These can guide the use of Co-Cr alloy in dentistry. MATERIAL AND METHODS: Co-Cr-Mo-W alloys were fabricated with a dimension of 45×2×2 mm by investment casting and SLM. The 3-point bend test measured the ultimate bend strength with 3 specimens in each group. The 4-point bend fatigue test evaluated the fatigue life under various stresses, with 6 specimens in each group. The specimens were mechanically ground, polished, and electrochemically etched. Scanning electron microscopy was used to identify the microstructures of both etched specimens and fracture surfaces. X-ray diffraction investigations were used to determine the phases. Significant differences in the bend strength were analyzed by using the independent samples t test (α=.05), and the fatigue test was analyzed with ANCOVA (α=.05). RESULTS: The mean ±standard deviation bend strength of SLM specimens was 1837 ±3 MPa, higher than the 1200 ±6 MPa for CAST specimens (P<.05). The maximum bend stress of the SLM specimens without fatigue failure was 735 MPa, which was statistically higher than the 394 MPa for CAST specimens (P<.05). The microstructure characteristics of the SLM alloy contributed to its excellent fatigue performance. In SLM alloy, the γ phase constituted the majority with some ε and Laves phases, while the cast alloy possessed higher ε and Laves phases. The grains of SLM alloy were equiaxed and fine, and the second phases were fine and dispersive. In contrast, the cast alloy possessed clear dendrites, and the second phases were sizable. CONCLUSIONS: The SLM dental Co-Cr-Mo-W alloy had statistically better 4-point bend fatigue properties than cast alloy, which was associated with an improved microstructure.

Design, Preparation, and Evaluation of Osthol Poly-Butyl-Cyanoacrylate Nanoparticles with Improved In Vitro Anticancer Activity in Neuroblastoma Treatment.

Osthol (osthole), known as a neuroprotective drug, has shown potent anticancer activity. However, the potential clinical application of osthol is limited due to its low water solubility and low bioavailability. Polybutyl cyanoacrylate (PBCA) has been widely used to improve the solubility of drugs with poor water solubility. In this study, an orthogonal experimental design (OED) was applied to design the preparation process of PBCA nanoparticles (NPs). Then, nanoparticles were prepared and evaluated in terms of physicochemical properties, in vitro release, and cellular uptake, etc. Further, the anti-cancer activity of osthol-PBCA NPs was demonstrated in SH-SY5Y cells. The pharmacokinetics and area under the curve (AUC) were investigated. The obtained osthol-NPs presented a spherical shape with a particle size of 110 ± 6.7 nm, a polydispersity index (PDI) of 0.126, and a zeta potential of −13 ± 0.32 mV. Compared with the free osthol, the drugs in osthol-NPs presented better stability and sustained release pattern activity. In vitro analysis using SH-SY5Y neuroblastoma cells showed that osthol-loaded nanoparticles displayed a significantly enhanced intracellular absorption process (three times) and cytotoxicity compared with free osthol (p < 0.05, increased 10−20%). The in vivo pharmacokinetic study revealed that the AUC of osthol-NPs was 3.3-fold higher than that of free osthol. In conclusion, osthol-PBCA NPs can enhance the bioactivity of osthol, being proposed as a novel, promising vehicle for drug delivery.

Combining 'grafting to' and 'grafting from' to synthesize comb-like NCC-g-PLA as a macromolecular modifying agent of PLA.

The surface modification of nano particles is very important in nanotechnology. Grafting from (GF) and grafting to (GT) are two main methods to prepare surface modified nanoparticles like nanocellulose crystalline (NCC) grafted with polylactic acid (PLA) chains. In the GF method, the NCC can get high grafting degree but short side chains to improve its compatibility with the polymer matrix. The GT method can help obtain long side chains to increase the chain entanglements but owns low grafting density. To take the advantage of both methods, a mixed modification method combining GT and GF methods was put forward to synthesize comb-like NCC-g-PLA (NP) as a macromolecular modifying agent of PLA. Firstly, GT Method was used to obtain long side-chain NP to improve chain entanglement. Secondly, the GF method was applied to obtain NP-g-PLA (NPL) and NP-g-PDLA (NPD) with additional short side chains to improve its dispersion and compatibility in the PLA matrix. The products showed an enhanced nucleation effect, the degree of crystallinity (Xc) of PLA composites increased almost four times with only 1 wt% NPD or NPL. What's more, the storage modulus and loss modulus of the composite melts also increased with 1 wt% NPL or NPD. The NPD/PLA shows a higher effect than NPL/PLA owning to stronger interaction originated from the stereocomplex (SC) network of PLA matrix with PDLA short chains in NPD.