Whole-Tumor Clearing and Imaging of Intratumor Microbiota in Three Dimensions with miCDaL Strategy.

Acquiring detailed spatial information about intratumor microbiota in situ is challenging, which leaves 3D distributions of microbiota within entire tumors largely unexplored. Here, a modified iDISCO-CUBIC tissue clearing and D-amino acid microbiome labeling-based (miCDaL) strategy are proposed, that integrates microbiota in situ labeling, tissue clearing, and whole-mount tissue imaging to enable 3D visualization of indigenous intratumor microbiota. Leveraging whole-mount spatial resolution and centimeter-scale imaging depth, the 3D biogeography of microbiota is successfully charted across various tumors at different developmental stages, providing quantitative spatial insights in relation to host tumors. By incorporating an immunostaining protocol, 3D imaging of the immunologic microenvironment is achieved in both murine and human mammary tumors that is previously assumed to be bacteria-free. Notably, immune infiltrates, including T cells and NK cells, and tertiary lymphoid structures are conspicuously absent in bacteria-colonized regions. This 3D imaging strategy for mapping Indigenous intratumor microbiota offers valuable insights into host-microbiota interactions.

Lanthanum-based dendritic mesoporous nanoplatform for tumor microenvironment activating synergistic anti-glioma efficacy.

Lanthanum (La)-based nanotherapeutics are therapeutically advantageous due to cytoplasmic oxygen species (ROS) levels for mediating intrinsic and extrinsic tumor cell apoptosis. While they have not been extensively explored for their potential to suppress malignancies in vivo. Correspondingly, we have formulated a unique lanthanum nanocarrier with high specific surface area, dendritic-divergent mesopores, importantly, exposing more active lanthanum sites. After surface PEGlytion and ICG loading in mesoporous channels, this fantastic nanoplatform can efficaciously enrich in malignant glioblastoma regions. Meaningfully, it can be sensitively dissociated for La ions release under weak acid (pH = 6.5) tumor microenvironment. Upon 808 nm light irradiation, high light-heat conversion efficiency is further proved, then this satisfied thermal in the tumor site progressively enhances ROS production by La ions. Owing to the synergistic oxidative therapy and photothermal therapy of our dendritic La nanoplatform, glioblastoma is efficaciously and synergistically prevented both in vitro and in vivo. All outcomes highlight the therapeutic potency of La based nanoplatform with radial mesopores to treat malignant cancer in vivo and encourage future translational exploration.

Biosynthesis of Diverse Ephedra-Type Alkaloids via a Newly Identified Enzymatic Cascade.

Ephedra-type alkaloids represent a large class of natural and synthetic phenylpropanolamine molecules with great pharmaceutical values. However, the existing methods typically rely on chemical approaches to diversify the N-group modification of Ephedra-type alkaloids. Herein, we report a 2-step enzymatic assembly line for creating structurally diverse Ephedra-type alkaloids to replace the conventional chemical modification steps. We first identified a new carboligase from Bacillus subtilis (BsAlsS, acetolactate synthase) as a robust catalyst to yield different phenylacetylcarbinol (PAC) analogs from diverse aromatic aldehydes with near 100% conversions. Subsequently, we screened imine reductases (IREDs) for the reductive amination of PAC analogs. It was found that IRG02 from Streptomyces albidoflavus had good activities with conversions ranging from 37% to 84% for the reductive alkylamination with diverse amine partners such as allylamine, propargylamine, and cyclopropylamine. Overall, 3 new bio-modifications at the N-group of Ephedra-type alkaloids were established. Taken together, our work lays a foundation for the future implementation of biocatalysis for synthesizing structurally diverse Ephedra-type alkaloids with potential new pharmaceutical applications.

Algicidal bacteria-derived membrane vesicles as shuttles mediating cross-kingdom interactions between bacteria and algae.

Bacterial membrane vesicles (BMVs) are crucial biological vehicles for facilitating interspecies and interkingdom interactions. However, the extent and mechanisms of BMV involvement in bacterial-algal communication remain elusive. This study provides evidence of BMVs delivering cargos to targeted microalgae. Membrane vesicles (MVs) from Chitinimonas prasina LY03 demonstrated an algicidal profile similar to strain LY03. Further investigation revealed Tambjamine LY2, an effective algicidal compound, selectively packaged into LY03-MVs. Microscopic imaging demonstrated efficient delivery of Tambjamine LY2 to microalgae Heterosigma akashiwo and Thalassiosira pseudonana through membrane fusion. In addition, the study demonstrated the versatile cargo delivery capabilities of BMVs to algae, including the transfer of MV-carried nucleic acids into algal cells and the revival of growth in iron-depleted microalgae by MVs. Collectively, our findings reveal a previously unknown mechanism by which algicidal bacteria store hydrophobic algicidal compounds in MVs to trigger target microalgae death and highlight BMV potency in understanding and engineering bacterial-algae cross-talk.

AMPK targets PDZD8 to trigger carbon source shift from glucose to glutamine.

The shift of carbon utilization from primarily glucose to other nutrients is a fundamental metabolic adaptation to cope with decreased blood glucose levels and the consequent decline in glucose oxidation. AMP-activated protein kinase (AMPK) plays crucial roles in this metabolic adaptation. However, the underlying mechanism is not fully understood. Here, we show that PDZ domain containing 8 (PDZD8), which we identify as a new substrate of AMPK activated in low glucose, is required for the low glucose-promoted glutaminolysis. AMPK phosphorylates PDZD8 at threonine 527 (T527) and promotes the interaction of PDZD8 with and activation of glutaminase 1 (GLS1), a rate-limiting enzyme of glutaminolysis. In vivo, the AMPK-PDZD8-GLS1 axis is required for the enhancement of glutaminolysis as tested in the skeletal muscle tissues, which occurs earlier than the increase in fatty acid utilization during fasting. The enhanced glutaminolysis is also observed in macrophages in low glucose or under acute lipopolysaccharide (LPS) treatment. Consistent with a requirement of heightened glutaminolysis, the PDZD8-T527A mutation dampens the secretion of pro-inflammatory cytokines in macrophages in mice treated with LPS. Together, we have revealed an AMPK-PDZD8-GLS1 axis that promotes glutaminolysis ahead of increased fatty acid utilization under glucose shortage.

Entanglement Added to Cross-Linked Chains Enables Tough Gelatin-Based Hydrogel for Zn Metal Batteries.

Currently, it is still challenging to develop a hydrogel electrolyte matrix that can successfully achieve a harmonious combination of mechanical strength, ionic conductivity, and interfacial adaptability. Herein, a multi-networked hydrogel electrolyte with a high entanglement effect based on gelatin/oxidized dextran/methacrylic anhydride, denoted as ODGelMA is constructed. Attribute to the Schiff base network formulation of ─RC═N─, oxidized dextran integrated gelatin chains induce a dense hydrophilic conformation group. Furthermore, addition of methacrylic anhydride through a grafting process, the entangled hydrogel achieves impressive mechanical features (6.8 MPa tensile strength) and high ionic conductivity (3.68 mS cm-1 at 20 °C). The ODGelMA electrolyte regulates the zinc electrode by circumventing dendrite growth, and showcases an adaptable framework reservoir to accelerate the Zn2+ desolvation process. Benefiting from the entanglement effect, the Zn anode achieves an outstanding average Coulombic efficiency (CE) of 99.8% over 500 cycles and cycling stability of 900 h at 5 mA cm-2 and 2.5 mAh cm-2. The Zn||I2 full cell yields an ultra-long cycling stability of 10 000 cycles with a capacity retention of 92.4% at 5 C. Furthermore, a 60 mAh single-layer pouch cell maintains a stable work of 350 cycles.

Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia.

OBJECTIVE: In B-cell acute lymphoblastic leukemia (B-ALL), current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50% of cases, underscoring the urgent need for new therapeutic regimens for this patient population. The present study aimed to determine whether HZX-02-059, a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) and tubulin, is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients. METHODS: Cell proliferation, vacuolization, apoptosis, cell cycle, and in-vivo tumor growth were evaluated. In addition, Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL. RESULTS: HZX-02-059 was found to inhibit cell proliferation, induce vacuolization, promote apoptosis, block the cell cycle, and reduce in-vivo tumor growth. Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase (PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations. CONCLUSION: Overall, these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

SPAK inhibitor ZT-1a attenuates reactive astrogliosis and oligodendrocyte degeneration in a mouse model of vascular dementia.

BACKGROUND: Astrogliosis and white matter lesions (WML) are key characteristics of vascular contributions to cognitive impairment and dementia (VCID). However, the molecular mechanisms underlying VCID remain poorly understood. Stimulation of Na-K-Cl cotransport 1 (NKCC1) and its upstream kinases WNK (with no lysine) and SPAK (the STE20/SPS1-related proline/alanine-rich kinase) play a role in astrocytic intracellular Na+ overload, hypertrophy, and swelling. Therefore, in this study, we assessed the effect of SPAK inhibitor ZT-1a on pathogenesis and cognitive function in a mouse model of VCID induced by bilateral carotid artery stenosis (BCAS). METHODS: Following sham or BCAS surgery, mice were randomly assigned to receive either vehicle (DMSO) or SPAK inhibitor ZT-1a treatment regimen (days 14-35 post-surgery). Mice were then evaluated for cognitive functions by Morris water maze, WML by ex vivo MRI-DTI analysis, and astrogliosis/demyelination by immunofluorescence and immunoblotting. RESULTS: Compared to sham control mice, BCAS-Veh mice exhibited chronic cerebral hypoperfusion and memory impairments, accompanied by significant MRI DTI-detected WML and oligodendrocyte (OL) death. Increased activation of WNK-SPAK-NKCC1-signaling proteins was detected in white matter tissues and in C3d+ GFAP+ cytotoxic astrocytes but not in S100A10+ GFAP+ homeostatic astrocytes in BCAS-Veh mice. In contrast, ZT-1a-treated BCAS mice displayed reduced expression and phosphorylation of NKCC1, decreased astrogliosis, OL death, and WML, along with improved memory functions. CONCLUSION: BCAS-induced upregulation of WNK-SPAK-NKCC1 signaling contributes to white matter-reactive astrogliosis, OL death, and memory impairment. Pharmacological inhibition of the SPAK activity has therapeutic potential for alleviating pathogenesis and memory impairment in VCID.

Kirkendall effect-induced uniform stress distribution stabilizes nickel-rich layered oxide cathodes.

Nickel-rich layered oxide cathodes promise ultrahigh energy density but is plagued by the mechanical failure of the secondary particle upon (de)lithiation. Existing approaches for alleviating the structural degradation could retard pulverization, yet fail to tune the stress distribution and root out the formation of cracks. Herein, we report a unique strategy to uniformize the stress distribution in secondary particle via Kirkendall effect to stabilize the core region during electrochemical cycling. Exotic metal/metalloid oxides (such as Al2O3 or SiO2) is introduced as the heterogeneous nucleation seeds for the preferential growth of the precursor. The calcination treatment afterwards generates a dopant-rich interior structure with central Kirkendall void, due to the different diffusivity between the exotic element and nickel atom. The resulting cathode material exhibits superior structural and electrochemical reversibility, thus contributing to a high specific energy density (based on cathode) of 660 Wh kg-1 after 500 cycles with a retention rate of 86%. This study suggests that uniformizing stress distribution represents a promising pathway to tackle the structural instability facing nickel-rich layered oxide cathodes.

Deaggregation of mutant Plasmodium yoelii de-ubiquitinase UBP1 alters MDR1 localization to confer multidrug resistance.

Mutations in a Plasmodium de-ubiquitinase UBP1 have been linked to antimalarial drug resistance. However, the UBP1-mediated drug-resistant mechanism remains unknown. Through drug selection, genetic mapping, allelic exchange, and functional characterization, here we show that simultaneous mutations of two amino acids (I1560N and P2874T) in the Plasmodium yoelii UBP1 can mediate high-level resistance to mefloquine, lumefantrine, and piperaquine. Mechanistically, the double mutations are shown to impair UBP1 cytoplasmic aggregation and de-ubiquitinating activity, leading to increased ubiquitination levels and altered protein localization, from the parasite digestive vacuole to the plasma membrane, of the P. yoelii multidrug resistance transporter 1 (MDR1). The MDR1 on the plasma membrane enhances the efflux of substrates/drugs out of the parasite cytoplasm to confer multidrug resistance, which can be reversed by inhibition of MDR1 transport. This study reveals a previously unknown drug-resistant mechanism mediated by UBP1 through altered MDR1 localization and substrate transport direction in a mouse model, providing a new malaria treatment strategy.

Unveiling the State Transition Mechanisms of Ras Proteins through Enhanced Sampling and QM/MM Simulations.

In cells, wild-type RasGTP complexes exist in two distinct states: active State 2 and inactive State 1. These complexes regulate their functions by transitioning between the two states. However, the mechanisms underlying this state transition have not been clearly elucidated. To address this, we conducted a detailed simulation study to characterize the energetics of the stable states involved in the state transitions of the HRasGTP complex, specifically from State 2 to State 1. This was achieved by employing multiscale quantum mechanics/molecular mechanics and enhanced sampling molecular dynamics methods. Based on the simulation results, we constructed the two-dimensional free energy landscapes that provide crucial information about the conformational changes of the HRasGTP complex from State 2 to State 1. Furthermore, we also explored the conformational changes from the intermediate state to the product state during guanosine triphosphate hydrolysis. This study on the conformational changes involved in the HRas state transitions serves as a valuable reference for understanding the corresponding events of both KRas and NRas as well.

Targeting PRMT1-mediated SRSF1 methylation to suppress oncogenic exon inclusion events and breast tumorigenesis.

PRMT1 plays a vital role in breast tumorigenesis; however, the underlying molecular mechanisms remain incompletely understood. Herein, we show that PRMT1 plays a critical role in RNA alternative splicing, with a preference for exon inclusion. PRMT1 methylome profiling identifies that PRMT1 methylates the splicing factor SRSF1, which is critical for SRSF1 phosphorylation, SRSF1 binding with RNA, and exon inclusion. In breast tumors, PRMT1 overexpression is associated with increased SRSF1 arginine methylation and aberrant exon inclusion, which are critical for breast cancer cell growth. In addition, we identify a selective PRMT1 inhibitor, iPRMT1, which potently inhibits PRMT1-mediated SRSF1 methylation, exon inclusion, and breast cancer cell growth. Combination treatment with iPRMT1 and inhibitors targeting SRSF1 phosphorylation exhibits an additive effect of suppressing breast cancer cell growth. In conclusion, our study dissects a mechanism underlying PRMT1-mediated RNA alternative splicing. Thus, PRMT1 has great potential as a therapeutic target in breast cancer treatment.

Exploring Diversity through Dimerization in Natural Products by a Rational Tandem Mass-Based Molecular Network Strategy.

The step- and atom-efficient dimerization strategy is frequently used in nature to build structural complexity and diversity. We propose the rationale and structural features of the versatile monomers that are responsible for "diversity through dimerization". Using 5-FAM-maleimide combined with a UHPLC-MS/MS-FBMN workflow, we successfully identified a diverse set of dimeric natural products from fungus Panus rudis F01315, in which all four complex 4'5-ring scaffolds are derived from one monomeric epoxyquinol and endowed with functional diversity.

Discovery of urea-based pleuromutilin derivatives as potent gram-positive antibacterial agents.

There is an urgent need to discover new antibacterial drugs and provide new treatment options for clinical antimicrobial resistance (AMR) pathogen infections. Inspired by the structural insights from analyzing the co-crystal structure of lefamulin with the ribosomes of S. aureus, a series of novel pleuromutilin derivatives of phenylene sulfide incorporated with urea moiety were designed and synthesized. The structure-activity relationship (SAR) study revealed that derivatives with urea in the meta position of phenylene sulfide had optimal antibacterial activities in vitro. Among them, 21h was the most potent one against Methicillin-resistant Staphylococcus aureus (MRSA) and clinical AMR Gram-positive bacteria with minimum inhibitory concentrations (MICs) in the range of 0.00195-0.250 µg/mL. And it possessed low resistance frequency, prolonged Post-Antibiotic Effect and the capability to overcome lefamulin-induced resistance. Furthermore, 21h exhibited potent antibacterial activity in vivo in both the thigh infection model and trauma infection model, representing a promising lead for the development of new antibiotics against Gram-positive pathogens, especially for AMR bacteria.

Human Polo-like Kinase Inhibitors as Antiplasmodials.

Protein kinases have proven to be a very productive class of therapeutic targets, and over 90 inhibitors are currently in clinical use primarily for the treatment of cancer. Repurposing these inhibitors as antimalarials could provide an accelerated path to drug development. In this study, we identified BI-2536, a known potent human polo-like kinase 1 inhibitor, with low nanomolar antiplasmodial activity. Screening of additional PLK1 inhibitors revealed further antiplasmodial candidates despite the lack of an obvious orthologue of PLKs in Plasmodium. A subset of these inhibitors was profiled for their in vitro killing profile, and commonalities between the killing rate and inhibition of nuclear replication were noted. A kinase panel screen identified PfNEK3 as a shared target of these PLK1 inhibitors; however, phosphoproteome analysis confirmed distinct signaling pathways were disrupted by two structurally distinct inhibitors, suggesting PfNEK3 may not be the sole target. Genomic analysis of BI-2536-resistant parasites revealed mutations in genes associated with the starvation-induced stress response, suggesting BI-2536 may also inhibit an aminoacyl-tRNA synthetase.

Rational design of a polysaccharide-based viral mimicry nanocomplex for potent gene silencing in inflammatory tissues.

Rational design and fabrication of small interfering RNA (siRNA) delivery system with simple production scheme, specific targeting capability, responsiveness to endogenous stimuli and potential multi-functionalities remains technically challenging. Herein, we screen and design a virus-mimicking polysaccharide nanocomplex that shows specific gene delivery capability in a selective subset of leukocytes. A virus-inspired poly (alkyl methacrylate-co-methacrylic acid) fragment was conjugated on barley ß-glucans (EEPG) to endow the nanocomplex with pH-dependent endosomal membrane destabilization capabilities, as confirmed both biologically and computationally. siRNA loaded EEPG nanocomplex is feasibly fabricated in a single-step manner, which exhibit efficient gene silencing efficacy towards Dectin-1+ monocytes/macrophages. The inherent targeting affinity and feasible gene silencing potency of EEPG nanocomplex are investigated in three independent murine inflammation models, including myocardial infarction, lung fibrosis and acute liver damage. Significant enhanced accumulation level of EEPG nanocomplex is observed in cardiac lesion site, indicating its exclusive targeting capability for ischemic heart diseases. As a proof of concept, siTGF-ß based gene therapy is confirmed in murine model with heart fibrosis. Overall, our findings suggest the designed EEPG nanocomplex is favorable for siRNA delivery, which might have translational potential as a versatile platform in inflammation-related diseases.

Efficacy of novel SPAK inhibitor ZT-1a derivatives (1c, 1d, 1g & 1h) on improving post-stroke neurological outcome and brain lesion in mice.

SPAK inhibitor ZT-1a was previously shown to be neuroprotective in murine ischemic stroke models. In this study, we further examined the efficacy of four ZT-1a derivatives (ZT-1c, -1d, -1g and -1h) on reducing stroke-induced sensorimotor function impairment and brain lesions. Vehicle control (Veh) or ZT-1 derivatives were administered via osmotic pump to adult C57BL/6J mice during 3-21 h post-stroke. Neurological behavior of these mice was assessed at days 1, 3, 5, and 7 post-stroke and MRI T2WI and DTI analysis was subsequently conducted in ex vivo brains. Veh-treated stroke mice displayed sensorimotor function deficits compared to Sham mice. In contrast, mice receiving ZT-1a derivatives displayed significantly lower neurological deficits at days 3-7 post-stroke (p < 0.05), with ZT-1a, ZT-1c and ZT-1d showing greater impact than ZT-1h and ZT-1g. ZT-1a treatment was the most effective in reducing brain lesion volume on T2WI and in preserving NeuN + neurons (p < 0.01), followed by ZT-1d > -1c > -1g > -1h. The Veh-treated stroke mice displayed white matter tissue injury, reflected by reduced fractional anisotropy (FA) or axial diffusivity (AD) values in external capsule, internal capsule and hippocampus. In contrast, only ZT-1a-as well as ZT-1c-treated stroke mice exhibited significantly higher FA and AD values. These findings demonstrate that post-stroke administration of SPAK inhibitor ZT-1a and its derivatives (ZT-1c and ZT-1d) is effective in protecting gray and white matter tissues in ischemic brains, showing a potential for ischemic stroke therapy development.

Bicyclomycin Activity against Multidrug-Resistant Gram-Negative Pathogens.

The growing prevalence of antimicrobial resistance poses a grave threat to human health. Among the most difficult bacterial infections to treat are those caused by multidrug-resistant (MDR) Gram-negative pathogens because few effective regimens are available. One approach to this problem is to find ways to increase the activity of old antimicrobials that had seen limited application. Bicyclomycin, an inhibitor of transcription termination, is an example in which the additional inhibition of protein or RNA synthesis increases bicyclomycin-mediated lethality against Gram-negative bacteria. To examine the potential of bicyclomycin for the treatment of MDR bacterial pathogens, we first measured the MICs of bicyclomycin and other widely used antimicrobials against more than 100 multidrug-resistant Gram-negative clinical isolates. Bicyclomycin showed good coverage of carbapenem-resistant Enterobacteriaceae (CRE) and Escherichia coli (MIC50/MIC90 of 25/50 µg/mL for both bacteria) and moderate activity against Klebsiella pneumoniae (MIC50/MIC90 of 50/200 µg/mL). Bicyclomycin also exhibited synergy (e.g., fractional inhibitory concentration [FIC] index of <0.5) with doxycycline for the inhibition of bacterial growth by a checkerboard assay. Although bicyclomycin exhibited very weak lethality by itself, it showed synthetic lethality with doxycycline against K. pneumoniae: the combination killed 100- to 1,000-fold more bacteria than either agent alone. In a murine model of infection, the bicyclomycin-doxycycline combination showed better efficacy than either agent alone, and the combination treatment largely eliminated histopathological manifestations caused by infection. Thus, bicyclomycin, which has largely been limited to the treatment of Gram-negative digestive tract infections, can now be considered for the combination treatment of systemic multidrug-resistant infections caused by CRE, E. coli, and K. pneumoniae. IMPORTANCE As antimicrobial resistance continues to increase, options for effectively treating multidrug-resistant (MDR) Gram-negative infections are declining. Finding ways to enhance the lethality of old agents that have unique molecular targets is important because developing new antimicrobials is becoming increasingly difficult. The present work showed that the old antibiotic bicyclomycin has good bacteriostatic activity against multiple clinical isolates of three significant types of MDR Gram-negative pathogens frequently encountered in hospital infections, as required for the consideration of expanded indications. More significant is the synergistic growth-inhibitory effect and the enhancement of killing by the additional presence of doxycycline since this increases the in vivo efficacy. These data demonstrate that bicyclomycin-containing regimens have potential as new treatment options for MDR Gram-negative infections such as those caused by CRE, E. coli, and K. pneumoniae.

Epidemiological study of capillary malformation among 7299 infants under 1 year of age in China.

BACKGROUND: Capillary malformation (CM) is the most common vascular malformation. Large scale studies on its incidence and risk factors are limited in China. OBJECTIVE: Our study aimed to investigate the incidence of CM in Chinese infants and to evaluate its potential risk factors. METHODS: A cross-sectional study, including 7299 infants (aged < 1 year) were collected by a self-administered questionnaire. Independent-samples T tests or χ2 tests and multivariable logistic models were used to examine the potential risk factors for CM. RESULTS: The incidences of salmon patches and port-wine stains (PWSs) were 9.10% and 0.80%, respectively. In analyses, male sex (OR: 1.32, 95% CI: 1.12-1.55) and birth hypoxia (OR: 5.61, 95% CI: 4.39-7.16) were risk factors for salmon patches. Birth hypoxia (OR: 12.58, 95% CI: 7.26-21.79) and pregnancy-induced hypertension syndrome (PIH; OR: 3.66, 95% CI: 1.49-8.99) were associated with a higher risk of PWSs. CONCLUSION: This epidemiological study had the largest sample size of infants with CM in the world thus far, which updated its incidence in Chinese infants and found the potential risk factors for CM.

Marine self-potential measurement tool for autonomous underwater vehicle.

Marine self-potential (SP) measurement is commonly conducted for seafloor sulfide detection and hydrothermal vent studies in deep water using instruments towed close to the seafloor. However, this method has the following shortcomings: (1) It relies on ships for deep towing, and the need for a dedicated ship time lowers its efficiency. (2) Owing to complex topography, most towed instruments are located far from the seafloor to ensure safety, resulting in large effective signal attenuation and low signal-to-noise ratio. (3) The measurement direction is generally a single axis, with only the electric field of the axial component observed, providing limited information. With the gradual maturity of autonomous underwater vehicle (AUV) technology, it has become possible to mount marine SP measurement tools on AUVs for detection. Compared with conventional methods, this method has significant advantages in terms of efficiency, signal-to-noise ratio, and multicomponent observation. The proposed tool is a lightweight underwater device having a compact design and low power consumption, making it suitable for AUVs. The overall volume of the tool is D50 mm × L350 mm, and the underwater weight is 0.6 kg. Chopper amplification technology ensures the low-noise measurement of electric field signals. In addition, the reformed electrodes enhance stability, thereby reducing the mechanical vibration noise. Laboratory test results show that the noise of the data logger is 7.8 nV/rt (Hz)@1 Hz. The marine test conducted in the southwest Indian Ocean verified the reliability of the proposed marine SP measurement tool. The maximum working depth was 4000 m. The test lasted ∼25 h, and the effective electric field data were collected for ∼17 h. This survey found a maximum SP anomaly of 0.55 mV/m in the Yuhuang hydrothermal field, which provided effective data support for the discovery of new seafloor sulfide anomalies.