TMCO1 Is an ER Ca(2+) Load-Activated Ca(2+) Channel.

Maintaining homeostasis of Ca(2+) stores in the endoplasmic reticulum (ER) is crucial for proper Ca(2+) signaling and key cellular functions. The Ca(2+)-release-activated Ca(2+) (CRAC) channel is responsible for Ca(2+) influx and refilling after store depletion, but how cells cope with excess Ca(2+) when ER stores are overloaded is unclear. We show that TMCO1 is an ER transmembrane protein that actively prevents Ca(2+) stores from overfilling, acting as what we term a "Ca(2+) load-activated Ca(2+) channel" or "CLAC" channel. TMCO1 undergoes reversible homotetramerization in response to ER Ca(2+) overloading and disassembly upon Ca(2+) depletion and forms a Ca(2+)-selective ion channel on giant liposomes. TMCO1 knockout mice reproduce the main clinical features of human cerebrofaciothoracic (CFT) dysplasia spectrum, a developmental disorder linked to TMCO1 dysfunction, and exhibit severe mishandling of ER Ca(2+) in cells. Our findings indicate that TMCO1 provides a protective mechanism to prevent overfilling of ER stores with Ca(2+) ions.

AGIDB: a versatile database for genotype imputation and variant decoding across species.

The high cost of large-scale, high-coverage whole-genome sequencing has limited its application in genomics and genetics research. The common approach has been to impute whole-genome sequence variants obtained from a few individuals for a larger population of interest individually genotyped using SNP chip. An alternative involves low-coverage whole-genome sequencing (lcWGS) of all individuals in the larger population, followed by imputation to sequence resolution. To overcome limitations of processing lcWGS data and meeting specific genotype imputation requirements, we developed AGIDB (https://agidb.pro), a website comprising tools and database with an unprecedented sample size and comprehensive variant decoding for animals. AGIDB integrates whole-genome sequencing and chip data from 17 360 and 174 945 individuals, respectively, across 89 species to identify over one billion variants, totaling a massive 688.57 TB of processed data. AGIDB focuses on integrating multiple genotype imputation scenarios. It also provides user-friendly searching and data analysis modules that enable comprehensive annotation of genetic variants for specific populations. To meet a wide range of research requirements, AGIDB offers downloadable reference panels for each species in addition to its extensive dataset, variant decoding and utility tools. We hope that AGIDB will become a key foundational resource in genetics and breeding, providing robust support to researchers.

Integrated analysis of genome-wide association studies and 3D epigenomic characteristics reveal the BMP2 gene regulating loin muscle depth in Yorkshire pigs.

BACKGROUND: The lack of integrated analysis of genome-wide association studies (GWAS) and 3D epigenomics restricts a deep understanding of the genetic mechanisms of meat-related traits. With the application of techniques as ChIP-seq and Hi-C, the annotations of cis-regulatory elements in the pig genome have been established, which offers a new opportunity to elucidate the genetic mechanisms and identify major genetic variants and candidate genes that are significantly associated with important economic traits. Among these traits, loin muscle depth (LMD) is an important one as it impacts the lean meat content. In this study, we integrated cis-regulatory elements and genome-wide association studies (GWAS) to identify candidate genes and genetic variants regulating LMD. RESULTS: Five single nucleotide polymorphisms (SNPs) located on porcine chromosome 17 were significantly associated with LMD in Yorkshire pigs. A 10 kb quantitative trait locus (QTL) was identified as a candidate functional genomic region through the integration of linkage disequilibrium and linkage analysis (LDLA) and high-throughput chromosome conformation capture (Hi-C) analysis. The BMP2 gene was identified as a candidate gene for LMD based on the integrated results of GWAS, Hi-C meta-analysis, and cis-regulatory element data. The identified QTL region was further verified through target region sequencing. Furthermore, through using dual-luciferase assays and electrophoretic mobility shift assays (EMSA), two SNPs, including SNP rs321846600, located in the enhancer region, and SNP rs1111440035, located in the promoter region, were identified as candidate SNPs that may be functionally related to the LMD. CONCLUSIONS: Based on the results of GWAS, Hi-C, and cis-regulatory elements, the BMP2 gene was identified as an important candidate gene regulating variation in LMD. The SNPs rs321846600 and rs1111440035 were identified as candidate SNPs that are functionally related to the LMD of Yorkshire pigs. Our results shed light on the advantages of integrating GWAS with 3D epigenomics in identifying candidate genes for quantitative traits. This study is a pioneering work for the identification of candidate genes and related genetic variants regulating one key production trait (LMD) in pigs by integrating genome-wide association studies and 3D epigenomics.

African swine fever virus I73R is a critical virulence-related gene: A potential target for attenuation.

African swine fever virus (ASFV) is a large, double-stranded DNA virus that causes a fatal disease in pigs, posing a threat to the global pig industry. Whereas some ASFV proteins have been found to play important roles in ASFV-host interaction, the functional roles of many proteins are still largely unknown. In this study, we identified I73R, an early viral gene in the replication cycle of ASFV, as a key virulence factor. Our findings demonstrate that pI73R suppresses the host innate immune response by broadly inhibiting the synthesis of host proteins, including antiviral proteins. Crystallization and structural characterization results suggest that pI73R is a nucleic-acid-binding protein containing a Zα domain. It localizes in the nucleus and inhibits host protein synthesis by suppressing the nuclear export of cellular messenger RNA (mRNAs). While pI73R promotes viral replication, the deletion of the gene showed that it is a nonessential gene for virus replication. In vivo safety and immunogenicity evaluation results demonstrate that the deletion mutant ASFV-GZΔI73R is completely nonpathogenic and provides effective protection to pigs against wild-type ASFV. These results reveal I73R as a virulence-related gene critical for ASFV pathogenesis and suggest that it is a potential target for virus attenuation. Accordingly, the deletion mutant ASFV-GZΔI73R can be a potent live-attenuated vaccine candidate.

African swine fever virus pB475L evades host antiviral innate immunity via targeting STAT2 to inhibit IFN-I signaling.

African swine fever virus (ASFV) causes severe disease in domestic pigs and wild boars, seriously threatening the development of the global pig industry. Type I interferon (IFN-I) is an important component of innate immunity, inducing the transcription and expression of antiviral cytokines by activating Janus-activated kinase-signal transducer and activator of transcription (STAT). However, the underlying molecular mechanisms by which ASFV antagonizes IFN-I signaling have not been fully elucidated. Therefore, using coimmunoprecipitation, confocal microscopy, and dual luciferase reporter assay methods, we investigated these mechanisms and identified a novel ASFV immunosuppressive protein, pB475L, which interacts with the C-terminal domain of STAT2. Consequently, pB475L inhibited IFN-I signaling by inhibiting STAT1 and STAT2 heterodimerization and nuclear translocation. Furthermore, we constructed an ASFV-B475L7PM mutant strain by homologous recombination, finding that ASFV-B475L7PM attenuated the inhibitory effects on IFN-I signaling compared to ASFV-WT. In summary, this study reveals a new mechanism by which ASFV impairs host innate immunity.

Bi-allelic variants in neuronal cell adhesion molecule cause a neurodevelopmental disorder characterized by developmental delay, hypotonia, neuropathy/spasticity.

Cell adhesion molecules are membrane-bound proteins predominantly expressed in the central nervous system along principal axonal pathways with key roles in nervous system development, neural cell differentiation and migration, axonal growth and guidance, myelination, and synapse formation. Here, we describe ten affected individuals with bi-allelic variants in the neuronal cell adhesion molecule NRCAM that lead to a neurodevelopmental syndrome of varying severity; the individuals are from eight families. This syndrome is characterized by developmental delay/intellectual disability, hypotonia, peripheral neuropathy, and/or spasticity. Computational analyses of NRCAM variants, many of which cluster in the third fibronectin type III (Fn-III) domain, strongly suggest a deleterious effect on NRCAM structure and function, including possible disruption of its interactions with other proteins. These findings are corroborated by previous in vitro studies of murine Nrcam-deficient cells, revealing abnormal neurite outgrowth, synaptogenesis, and formation of nodes of Ranvier on myelinated axons. Our studies on zebrafish nrcamaΔ mutants lacking the third Fn-III domain revealed that mutant larvae displayed significantly altered swimming behavior compared to wild-type larvae (p < 0.03). Moreover, nrcamaΔ mutants displayed a trend toward increased amounts of α-tubulin fibers in the dorsal telencephalon, demonstrating an alteration in white matter tracts and projections. Taken together, our study provides evidence that NRCAM disruption causes a variable form of a neurodevelopmental disorder and broadens the knowledge on the growing role of the cell adhesion molecule family in the nervous system.

Phenylthiol-BODIPY-based supramolecular metallacycles for synergistic tumor chemo-photodynamic therapy.

The development of more effective tumor therapy remains challenging and has received widespread attention. In the past decade, there has been growing interest in synergistic tumor therapy based on supramolecular coordination complexes. Herein, we describe two triangular metallacycles (1 and 2) constructed by the formation of pyridyl boron dipyrromethene (BODIPY)-platinum coordination. Metallacycle 2 had considerable tumor penetration, as evidenced by the phenylthiol-BODIPY ligand imparting red fluorescent emission at ∼660 nm, enabling bioimaging, and transport visualization within the tumor. Based on the therapeutic efficacy of the platinum(II) acceptor and high singlet oxygen (1O2) generation ability of BODIPY, 2 was successfully incorporated into nanoparticles and applied in chemo-photodynamic tumor therapy against malignant human glioma U87 cells, showing excellent synergistic therapeutic efficacy. A half-maximal inhibitory concentration of 0.35 µM was measured for 2 against U87 cancer cells in vitro. In vivo experiments indicated that 2 displayed precise tumor targeting ability and good biocompatibility, along with strong antitumor effects. This work provides a promising approach for treating solid tumors by synergistic chemo-photodynamic therapy of supramolecular coordination complexes.

Evolutionary divergence of duplicated genomes in newly described allotetraploid cottons.

Allotetraploid cotton (Gossypium) species represents a model system for the study of plant polyploidy, molecular evolution, and domestication. Here, chromosome-scale genome sequences were obtained and assembled for two recently described wild species of tetraploid cotton, Gossypium ekmanianum [(AD)6, Ge] and Gossypium stephensii [(AD)7, Gs], and one early form of domesticated Gossypium hirsutum, race punctatum [(AD)1, Ghp]. Based on phylogenomic analysis, we provide a dated whole-genome level perspective for the evolution of the tetraploid Gossypium clade and resolved the evolutionary relationships of Gs, Ge, and domesticated G. hirsutum. We describe genomic structural variation that arose during Gossypium evolution and describe its correlates-including phenotypic differentiation, genetic isolation, and genetic convergence-that contributed to cotton biodiversity and cotton domestication. Presence/absence variation is prominent in causing cotton genomic structural variations. A presence/absence variation-derived gene encoding a phosphopeptide-binding protein is implicated in increasing fiber length during cotton domestication. The relatively unimproved Ghp offers the potential for gene discovery related to adaptation to environmental challenges. Expanded gene families enoyl-CoA δ isomerase 3 and RAP2-7 may have contributed to abiotic stress tolerance, possibly by targeting plant hormone-associated biochemical pathways. Our results generate a genomic context for a better understanding of cotton evolution and for agriculture.

Dissecting the pleiotropic roles of reactive oxygen species (ROS) in lung cancer: From carcinogenesis toward therapy.

Lung cancer is a major cause of morbidity and mortality. The specific pulmonary structure to directly connect with ambient air makes it more susceptible to damage from airborne toxins. External oxidative stimuli and endogenous reactive oxygen species (ROS) play a crucial role in promoting lung carcinogenesis and development. The biological properties of higher ROS levels in tumor cells than in normal cells make them more sensitive and vulnerable to ROS injury. Therefore, the strategy of targeting ROS has been proposed for cancer therapy for decades. However, it is embarrassing that countless attempts at ROS-based therapies have had very limited success, and no FDA approval in the anticancer list was mechanistically based on ROS manipulation. Even compared with the untargetable proteins, such as transcription factors, ROS are more difficult to be targeted due to their chemical properties. Thus, the pleiotropic roles of ROS provide therapeutic potential for anticancer drug discovery, while a better dissection of the mechanistic action and signaling pathways is a prerequisite for future breakthroughs. This review discusses the critical roles of ROS in cancer carcinogenesis, ROS-inspired signaling pathways, and ROS-based treatment, exemplified by lung cancer. In particular, an eight considerations rule is proposed for ROS-targeting strategies and drug design and development.

Contribution of FOS in neutrophils to venous thromboembolism via miR-144 based on bioinformatic prediction and validation.

The Finkel-Biskis-Jinkins Osteosarcoma (c-Fos; encoded by FOS) plays an important role in several cardiovascular diseases, including atherosclerosis and stroke. However, the relationship between FOS and venous thromboembolism (VTE) remains unknown. We identified differentially expressed genes in Gene Expression Omnibus dataset, GSE48000, comprising VTE patients and healthy individuals, and analysed them using CIBERSORT and weighted co-expression network analysis (WGCNA). FOS and CD46 expressions were significantly downregulated (FOS p = 2.26E-05, CD64 p = 8.83E-05) and strongly linked to neutrophil activity in VTE. We used GSE19151 and performed PCR to confirm that FOS and CD46 had diagnostic potential for VTE; however, only FOS showed differential expression by PCR and ELISA in whole blood samples. Moreover, we found that hsa-miR-144 which regulates FOS expression was significantly upregulated in VTE. Furthermore, FOS expression was significantly downregulated in neutrophils of VTE patients (p = 0.03). RNA sequencing performed on whole blood samples of VTE patients showed that FOS exerted its effects in VTE via the leptin-mediated adipokine signalling pathway. Our results suggest that FOS and related genes or proteins can outperform traditional clinical markers and may be used as diagnostic biomarkers for VTE.

Multicomponent, Multicavity Metallacages That Contain Different Binding Sites for Allosteric Recognition.

The encapsulation of different guest molecules by their different recognition domains of proteins leads to selective binding, catalysis, and transportation. Synthetic hosts capable of selectively binding different guests in their different cavities to mimic the function of proteins are highly desirable but challenging. Here, we report three ladder-shaped, triple-cavity metallacages prepared by multicomponent coordination-driven self-assembly. Interestingly, the porphyrin-based metallacage is capable of heteroleptic encapsulation of fullerenes (C60 or C70) and coronene using its different cavities, allowing distinct allosteric recognition of coronene upon the addition of C60 or C70. Owing to the different binding affinities of the cavities, the metallacage hosts one C60 molecule in the central cavity and two coronene units in the side cavities, while encapsulating two C70 molecules in the side cavities and one coronene molecule in the central cavity. The rational design of multicavity assemblies that enable heteroleptic encapsulation and allosteric recognition will guide the further design of advanced supramolecular constructs with tunable recognition properties.

Dense Multibutterfly Spots-Enhanced Miniaturized Optical Fiber Photoacoustic Gas Sensor.

A miniaturized optical fiber photoacoustic gas sensor enhanced by dense multibutterfly spots is reported for the first time. The principle of space light transmission of neglecting paraxial approximation is theoretically analyzed for designing a dense multibutterfly spots-based miniature multipass cell. In a multipass photoacoustic tube with a diameter of 16 mm, the light beam is reflected about a hundred times. The light spots on the mirror surfaces at both ends of the photoacoustic tube form a dense multibutterfly distribution. The volume of the micro multipass gas chamber is only 5.3 mL. An optical fiber cantilever based on F-P interference is utilized as a photoacoustic pressure detector. Compared with that of the single-pass structure, the gas detection ability of the photoacoustic system with dense multibutterfly spots is improved by about 50 times. The proposed miniaturized sensor realizes a detection limit of 3.4 ppb for C2H2 gas with an averaging time of 100 s. The recognized coefficients of minimum detectable absorption (αmin) and normalized noise equivalent absorption are 1.9 × 10-8 cm-1 and 8.4 × 10-10 W cm-1 Hz-1/2, respectively.

Fiber-Optic Photoacoustic CO Sensor for Gas Insulation Equipment Monitoring Based on Cantilever Differential Lock-In Amplification and Optical Excitation Enhancement.

A fiber-optic photoacoustic CO sensor for gas insulation equipment is proposed, which relies on F-P interferometric cantilever-based differential lock-in amplification and optical multipass excitation enhancement. The sensor has excellent characteristics of high sensitivity, antielectromagnetic interference, fast response, and long-distance detection. The photoacoustic pressure waves in the two resonators of the differential photoacoustic cell (DPAC) are simultaneously detected by two fiber-optic interferometric cantilevers and processed differentially; thereby, the gas flow noise is effectively suppressed. Based on the comprehensive analysis of the superposition of photoacoustic excitation and multipass absorption, the diameter of the resonator is determined to be 6 mm. The optical power emitted by the 1566.6 nm distributed feedback laser is increased to 500 mW by an erbium-doped fiber amplifier. The near-infrared light is reflected 30 times in the multipass cell, which improves the order of magnitude of optical effective excitation. Due to the low sound velocity of SF6 gas, the resonant frequency of the DPAC with a resonator length of 80 mm is 760 Hz. The response time to CO/SF6 gas is 93 s with a flow rate of 500 sccm. The detection limit of the CO sensor is 53 ppb, which realizes the accurate and timely perception of the SF6 decomposition derivative CO and provides technical support for trouble-free operation of gas insulation equipment.

Fiber-Optic Photoacoustic Gas Microsensor Dual Enhanced by Helmholtz Resonator and Interferometric Cantilever.

A high-sensitivity fiber-optic photoacoustic (PA) gas microsensor is demonstrated with dual enhancement based on acoustics and detection. Due to the characteristic of small size, a Helmholtz resonator is integrated into a miniature PA sensor. The acoustically amplified PA signal is detected by a high-sensitivity fiber Fabry-Perot (F-P) interferometric cantilever. The first-order resonant frequencies of the interferometric cantilever and Helmholtz resonator are matched by subtle adjustments. The weak PA signal is significantly enhanced in a volume of only 0.35 mL, which breaks the volume limitation of the resonance modes in traditional PA sensing systems. To improve the resolution of the microsensor, a white light interferometry (WLI)-based spectral demodulation algorithm is utilized. The experimental results indicate that the minimum detection limit of acetylene (C2H2) drops to about 15 ppb with an averaging time of 100 s, corresponding to the normalized noise equivalent absorption (NNEA) coefficient of 2.7 × 10-9 W·cm-1·Hz-1/2. The dual resonance enhanced fiber-optic PA gas microsensor has the merits of high sensitivity, intrinsic safety, and compact structure.

Ultrahigh Sensitive Trace Gas Sensing System with Dual Fiber-Optic Cantilever Multiplexing-Based Differential Photoacoustic Detection.

An ultrahigh sensitive trace gas sensing system was presented with dual cantilever-based differential photoacoustic detection. By combining the double enhancement of multipass absorption and optical differential detection, the gas detection sensitivity was significantly improved. The dual-channel synchronous photoacoustic detection was realized by fiber-optic Fabry-Perot interference spectrum multiplexing. The photoacoustic signals detected by two fiber-optic cantilever microphones installed in a differential photoacoustic cell (DPAC) were out of phase, while the detected gas flow noises were in phase. The optical differential detection method achieved both highly sensitive optical interference measurement and differential noise suppression. In the multipass configuration, the interaction path between excitation light and target gas achieved 4.1 m, which improved the photoacoustic signal by an order of magnitude compared with a single reflection. The maximum gas flow allowed by the system based on the DPAC was 250 sccm, which realized the dynamic monitoring of H2S in the SF6 background. The detection limit for H2S in SF6 background was 5.1 ppb, which corresponds to the normalized noise equivalent absorption coefficient of 9 × 10-10 cm-1 W Hz-1/2.

High-Precision Multipass Fiber-Optic Photoacoustic Gas Analyzer Based on 2f/1f Wavelength Modulation Spectroscopy.

A self-calibration fiber-optic photoacoustic (PA) gas analyzer based on 2f/1f wavelength modulation spectroscopy (WMS) is proposed, which utilizes gas and solid multipass absorption enhancement. The laser light is incident obliquely on the cell wall, and one end of the cell is equipped with a highly reflective mirror. The gas analyzer takes full advantage of the miniature multipass PA cell, which enhances the absorption of gas and solid simultaneously. As a result, the double absorption enhancement of 1f and 2f PA signals are realized. A dual-channel lock-in white-light interferometer based on fiber-optic PA demodulation is designed to simultaneously extract the 1f and 2f PA signals detected by the silicon cantilever. The experimental results of methane gas detection show that the minimum detection limit (MDL) of the PA gas analyzer is 20 ppb when the integration time is 60 s. Moreover, the detection error of gas concentration is within 3% when the laser power is reduced by half. The fiber-optic PA gas analyzer eliminates the influence of changes in the laser power and optical path loss, which can be used for the high-precision detection of trace gases.

Weighted gene co-expression network analysis reveals hub genes regulating response to salt stress in peanut.

Peanut (Arachis hypogaea L.) is an important oilseed crop worldwide. However, soil salinization becomes one of the main limiting factors of peanut production. Therefore, developing salt-tolerant varieties and understanding the molecular mechanisms of salt tolerance is important to protect peanut yield in saline areas. In this study, we selected four peanut varieties with contrasting response to salt challenges with T1 and T2 being tolerance and S1 and S2 being susceptible. High-throughput RNA sequencing resulted in more than 314.63 Gb of clean data from 48 samples. We identified 12,057 new genes, 7,971of which have functional annotations. KEGG pathway enrichment analysis of uniquely expressed genes in salt-tolerant peanut revealed that upregulated genes in the root are involved in the MAPK signaling pathway, fatty acid degradation, glycolysis/gluconeogenesis, and upregulated genes in the shoot were involved in plant hormone signal transduction and the MAPK signaling pathway. Na+ content, K+ content, K+/ Na+, and dry mass were measured in root and shoot tissues, and two gene co-expression networks were constructed based on weighted gene co-expression network analysis (WGCNA) in root and shoot. In this study, four key modules that are highly related to peanut salt tolerance in root and shoot were identified, plant hormone signal transduction, phenylpropanoid biosynthesis, starch and sucrose metabolism, flavonoid biosynthesis, carbon metabolism were identified as the key biological processes and metabolic pathways for improving peanut salt tolerance. The hub genes include genes encoding ion transport (such as HAK8, CNGCs, NHX, NCL1) protein, aquaporin protein, CIPK11 (CBL-interacting serine/threonine-protein kinase 11), LEA5 (late embryogenesis abundant protein), POD3 (peroxidase 3), transcription factor, and MAPKKK3. There were some new salt-tolerant genes identified in peanut, including cytochrome P450, vinorine synthase, sugar transport protein 13, NPF 4.5, IAA14, zinc finger CCCH domain-containing protein 62, beta-amylase, fatty acyl-CoA reductase 3, MLO-like protein 6, G-type lectin S-receptor-like serine/threonine-protein kinase, and kinesin-like protein KIN-7B. The identification of key modules, biological pathways, and hub genes in this study enhances our understanding of the molecular mechanisms underlying salt tolerance in peanuts. This knowledge lays a theoretical foundation for improving and innovating salt-tolerant peanut germplasm.

Dipole-Dipole Tuned Electronic Reconfiguration of Defective Carbon Sites for Efficient Oxygen Reduction into H2O2.

Metal-free carbon-based materials are one of the most promising electrocatalysts toward 2-electron oxygen reduction reaction (2e-ORR) for on-site production of hydrogen peroxide (H2O2), which however suffer from uncontrollable carbonizations and inferior 2e-ORR selectivity. To this end, a polydopamine (PDA)-modified carbon catalyst with a dipole-dipole enhancement is developed via a calcination-free method. The H2O2 yield rate outstandingly reaches 1.8 mol gcat -1 h-1 with high faradaic efficiency of above 95% under a wide potential range of 0.4-0.7 VRHE, overwhelming most of carbon electrocatalysts. Meanwhile, within a lab-made flow cell, the synthesized ORR electrode features an exceptional stability for over 250 h, achieved a pure H2O2 production efficacy of 306 g kWh-1. By virtue of its industrial-level capabilities, the established flow cell manages to perform a rapid pulp bleaching within 30 min. The superior performance and enhanced selectivity of 2e-ORR is experimentally revealed and attributed to the electronic reconfiguration on defective carbon sites induced by non-covalent dipole-dipole influence between PDA and carbon, thereby prohibiting the cleavage of O-O in OOH intermediates. This proposed strategy of dipole-dipole effects is universally applicable over 1D carbon nanotubes and 2D graphene, providing a practical route to design 2e-ORR catalysts.

In Situ Local Band Engineering of Monolayer Graphene Using Triboelectric Plasma.

Graphene, a promising material with excellent properties, suffers from a major limitation in electronics due to its zero bandgap. The gas molecules adsorption has proven to be an effective approach for band regulation, which usually requires a harsh environment. Here, O2 - ions produced with triboelectric plasma are used for in situ regulation of graphene, and the switching ratio can reach 1010. The O2 - ions physical adsorption will reduce the Fermi-level (EF) of graphene. As the EF of graphene is lower than the lowest unoccupied molecular orbital (LUMO) level of O2-, the adsorption of O2 - changes from uniform physical adsorption to local chemical adsorption, thereby realizing the semiconductor properties of graphene. The local graphene bandgap is calculated to be 83.4 meV by the variable-temperature experiment. Furthermore, annealing treatment can restore to 1/10 of the initial conductance. The C─O bond formed by O2 - adsorption has low bond energy and is easy to desorb, while the C═O bond formed by adsorption on defects and edges has higher bond energy and is difficult to desorb. The study proposes a simple in situ method to investigate the microscopic process of O2 - adsorption on the graphene surface, demonstrating a new perspective for local energy band engineering of graphene.

Chemoproteomic strategy identifies PfUCHL3 as the target of halofuginone.

The human malaria parasite Plasmodium falciparum (P. falciparum) continues to pose a significant public health challenge, leading to millions of fatalities globally. Halofuginone (HF) has shown a significant anti-P. falciparum effect, suggesting its potential as a therapeutic agent for malaria treatment. In this study, we synthesized a photoaffinity labeling probe of HF to identify its direct target in P. falciparum. Our results reveal that ubiquitin carboxyl-terminal hydrolase 3 (PfUCHL3) acts as a crucial target protein of HF, which modulates parasite growth in the intraerythrocytic cycle. In particular, we discovered that HF potentially forms hydrogen bonds with the Leu10, Glu11, and Arg217 sites of PfUCHL3, thereby inducing an allosteric effect by promoting the embedding of the helix 6' region on the protein surface. Furthermore, HF disrupts the expression of multiple functional proteins mediated by PfUCHL3, specifically those that play crucial roles in amino acid biosynthesis and metabolism in P. falciparum. Taken together, this study highlights PfUCHL3 as a previously undisclosed druggable target of HF, which contributes to the development of novel anti-malarial agents in the future.