Clinical data mining: challenges, opportunities, and recommendations for translational applications.

Clinical data mining of predictive models offers significant advantages for re-evaluating and leveraging large amounts of complex clinical real-world data and experimental comparison data for tasks such as risk stratification, diagnosis, classification, and survival prediction. However, its translational application is still limited. One challenge is that the proposed clinical requirements and data mining are not synchronized. Additionally, the exotic predictions of data mining are difficult to apply directly in local medical institutions. Hence, it is necessary to incisively review the translational application of clinical data mining, providing an analytical workflow for developing and validating prediction models to ensure the scientific validity of analytic workflows in response to clinical questions. This review systematically revisits the purpose, process, and principles of clinical data mining and discusses the key causes contributing to the detachment from practice and the misuse of model verification in developing predictive models for research. Based on this, we propose a niche-targeting framework of four principles: Clinical Contextual, Subgroup-Oriented, Confounder- and False Positive-Controlled (CSCF), to provide guidance for clinical data mining prior to the model's development in clinical settings. Eventually, it is hoped that this review can help guide future research and develop personalized predictive models to achieve the goal of discovering subgroups with varied remedial benefits or risks and ensuring that precision medicine can deliver its full potential.

Exploring the extensin gene family: an updated genome-wide survey in plants and algae.

Extensins (EXTs), a class of hydroxyproline-rich glycoprotein with multiple Ser-Pro3-5 motifs, are known to play roles in cell wall reinforcement and environmental responses. EXTs with repetitive Tyr-X-Tyr (YXY) motifs for crosslinking are referred as crosslinking EXTs. Our comprehensive study spanned 194 algal and plant species, categorizing EXTs into seven subfamilies: classical extensins (EXT I and II), arabinogalactan-protein extensins (AGP-EXTs), proline-rich extensin-like receptor kinases (PERKs), leucine-rich repeat extensins (LRX I and II), formin homology (FH) domain-containing extensins (FH-EXTs), proline-rich, arabinogalactan proteins, conserved cysteines (PAC) domain-containing extensins (PAC I and II), and eight-cysteine motif (8CM)-containing extensins (8CM-EXTs). In the examined dataset, EXTs were detected ubiquitously in plants but infrequently in algae, except for one Coccomyxa and four Chlamydomonadales species. No crosslinking EXTs were found in Poales or certain Zingiberales species. Notably, the previously uncharacterized EXT II, PAC II, and liverwort-specific 8CM-EXTs were found to be crosslinking EXTs. EXT II, featuring repetitive YY motifs instead of the conventional YXY motif, was exclusively identified in Solanaceae. Furthermore, tandem genes encoding distinctive 8CM-EXTs specifically expressed in the germinating spores of Marchantia polymorpha. This updated classification of EXT types allows us to propose a plausible evolutionary history of EXT genes during the course of plant evolution.

Study on the regulatory mechanism of latent membrane protein 2A on GCNT3 expression in nasopharyngeal carcinoma.

O-Glycan synthesis enzyme glucosaminyl (N-acetyl) transferase 3 (GCNT3) is closely related to the occurrence and development of various cancers. However, the regulatory mechanism and function of GCNT3 in nasopharyngeal carcinoma (NPC) are still poorly understood. This study aims to explore the regulatory mechanism of EBV-encoded latent membrane protein 2A (LMP2A) on GCNT3 and the biological role of GCNT3 in NPC. The results show that LMP2A can activate GCNT3 through the mTORC1 pathway, and there is a positive feedback between the mTORC1 and GCNT3. GCNT3 regulates EMT progression by forming a complex with ZEB1 to promote cell migration. GCNT3 can also promote cell proliferation. These findings indicate that targeting the LMP2A-mTORC1-GCNT3 axis may represent a novel therapeutic target in NPC.

The Significant Role of New Particle Composition and Morphology on the HNO3-Driven Growth of Particles down to Sub-10 nm.

New particle formation and growth greatly influence air quality and the global climate. Recent CERN Cosmics Leaving OUtdoor Droplets (CLOUD) chamber experiments proposed that in cold urban atmospheres with highly supersaturated HNO3 and NH3, newly formed sub-10 nm nanoparticles can grow rapidly (up to 1000 nm h-1). Here, we present direct observational evidence that in winter Beijing with persistent highly supersaturated HNO3 and NH3, nitrate contributed less than ∼14% of the 8-40 nm nanoparticle composition, and overall growth rates were only ∼0.8-5 nm h-1. To explain the observed growth rates and particulate nitrate fraction, the effective mass accommodation coefficient of HNO3 (αHNO3) on the nanoparticles in urban Beijing needs to be 2-4 orders of magnitude lower than those in the CLOUD chamber. We propose that the inefficient uptake of HNO3 on nanoparticles is mainly due to the much higher particulate organic fraction and lower relative humidity in urban Beijing. To quantitatively reproduce the observed growth, we show that an inhomogeneous "inorganic core-organic shell" nanoparticle morphology might exist for nanoparticles in Beijing. This study emphasized that growth for nanoparticles down to sub-10 nm was largely influenced by their composition, which was previously ignored and should be considered in future studies on nanoparticle growth.

Novel LDLR variants affecting low density lipoprotein metabolism identified in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disease of lipid metabolism mainly caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Genetic detection of patients with FH help with precise diagnosis and treatment, thus reducing the risk of coronary heart disease (CHD) and other related diseases. The study aimed to identify the causative gene mutations in a Chinese FH family and reveal the pathogenicity and the mechanism of these mutations. METHODS AND RESULTS: Whole exome sequencing was performed in a patient with severe lipid metabolism dysfunction seeking fertility guidance from a Chinese FH family. Two LDLR variants c.1875 C > G (p.N625K; novel variant) and c.1448G > A (p.W483*) were identified in the family. Wildtype and mutant LDLR constructs were established by the site-direct mutagenesis technique. Functional studies were carried out by cell transfection to evaluate the impact of detected variants on LDLR activity. The two variants were proven to affect LDL uptake and binding, resulting in cholesterol clearance reduction to different degrees. According to The American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines, the W483* variant was classified as "Pathogenic", while the N625K variant as "VUS". CONCLUSIONS: Our results provide novel experimental evidence of functional alteration by LDLR variants identified in our study and expand the mutational spectrum of LDLR mutation induced FH.

Heterogeneous hydrochlorination of lipids mediated by fatty acids in an indoor environment.

Fatty acids from cooking fumes and hypochlorous acid (HOCl) released from indoor cleaning adversely affect respiratory health, but the molecular-level mechanism remains unclear. Here, the effect of cooking oil fumes [palmitic acid (PA), oleic acid (OA), and linoleic acid (LA)] on lung model phospholipid (POPG) hydrochlorination mediated by HOCl at the air-water interface of the hanged droplets was investigated. Interfacial hydrochlorination of POPG was impeded by OA and LA, while that of POPG was facilitated by PA. The effect on POPG hydrochlorination increased with the decrease in oil fume concentration. A potential mechanism with respect to the chain length of these oil fumes, regardless of their saturation, was proposed. PA with a short carbon chain looses the POPG packing and leads to the exposure of the C=C double bonds of POPG, whereas OA and LA with a long carbon chain hinder HOCl from reaching the C=C bonds of POPG. These results for short chain and low concentration dependence suggest that the decay of oil fumes or the conversion of short-chain species by indoor interfacial chemistry might be adverse to lung health. These results provide insights into the relationship between indoor multicomponent pollutants and the respiratory system.

STAT3 inhibition ameliorates renal interstitial inflammation in MRL/lpr mice with diffuse proliferative lupus nephritis.

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) is one of the most common and severe clinical syndromes of diffuse proliferative lupus nephritis (DPLN), of which poor prognosis is indicated by aggravated renal function deterioration. However, the specific therapy and mechanisms of AKI in DPLN remain to be explored. METHODS: The correlation between AKI and clinical pathological changes in DPLN patients was analyzed. Expression of STAT3 signaling was detected in MRL/lpr mice with DPLN using immunohistochemical staining and immunoblotting. Inhibition of STAT3 activation by combination therapy was assessed in MRL/lpr mice. RESULTS: Correlation analysis revealed only the interstitial leukocytes were significantly related to AKI in endocapillary DPLN patients. MRL/lpr mice treated with vehicle, which can recapitulate renal damages of DPLN patients, showed upregulation of STAT3, pSTAT3 and caspase-1 in renal cortex. FLLL32 combined with methylprednisolone therapy significantly inhibited the STAT3 activation, improved acute kidney damage, reduced the interstitial infiltration of inflammatory cells and decreased the AKI incidence in MRL/lpr mice. CONCLUSION: STAT3 activation may play an important role in the pathogenesis of DPLN and the development of AKI. Hence, STAT3 inhibition based on the combination of FLLL32 with methylprednisolone may represent a new strategy for treatment of DPLN with AKI.

Early blood immune molecular alterations in cynomolgus monkeys with a PSEN1 mutation causing familial Alzheimer's disease.

INTRODUCTION: More robust non-human primate models of Alzheimer's disease (AD) will provide new opportunities to better understand the pathogenesis and progression of AD. METHODS: We designed a CRISPR/Cas9 system to achieve precise genomic deletion of exon 9 in cynomolgus monkeys using two guide RNAs targeting the 3' and 5' intron sequences of PSEN1 exon 9. We performed biochemical, transcriptome, proteome, and biomarker analyses to characterize the cellular and molecular dysregulations of this non-human primate model. RESULTS: We observed early changes of AD-related pathological proteins (cerebrospinal fluid Aß42 and phosphorylated tau) in PSEN1 mutant (ie, PSEN1-ΔE9) monkeys. Blood transcriptome and proteome profiling revealed early changes in inflammatory and immune molecules in juvenile PSEN1-ΔE9 cynomolgus monkeys. DISCUSSION: PSEN1 mutant cynomolgus monkeys recapitulate AD-related pathological protein changes, and reveal early alterations in blood immune signaling. Thus, this model might mimic AD-associated pathogenesis and has potential utility for developing early diagnostic and therapeutic interventions. HIGHLIGHTS: A dual-guide CRISPR/Cas9 system successfully mimics AD PSEN1-ΔE9 mutation by genomic excision of exon 9. PSEN1 mutant cynomolgus monkey-derived fibroblasts exhibit disrupted PSEN1 endoproteolysis and increased Aß secretion. Blood transcriptome and proteome profiling implicate early inflammatory and immune molecular dysregulation in juvenile PSEN1 mutant cynomolgus monkeys. Cerebrospinal fluid from juvenile PSEN1 mutant monkeys recapitulates early changes of AD-related pathological proteins (increased Aß42 and phosphorylated tau).

Unlocking soil revival: the role of sulfate-reducing bacteria in mitigating heavy metal contamination.

Soil contamination with heavy metals from industrial and mining activities poses significant environmental and public health risks, necessitating effective remediation strategies. This review examines the utilization of sulfate-reducing bacteria (SRB) for bioremediation of heavy metal-contaminated soils. Specifically, it focuses on SRB metabolic pathways for heavy metal immobilization, interactions with other microorganisms, and integration with complementary remediation techniques such as soil amendments and phytoremediation. We explore the mechanisms of SRB action, their synergistic relationships within soil ecosystems, and the effectiveness of combined remediation approaches. Our findings indicate that SRB can effectively immobilize heavy metals by converting sulfate to sulfide, forming stable metal sulfides, thereby reducing the bioavailability and toxicity of heavy metals. Nevertheless, challenges persist, including the need to optimize environmental conditions for SRB activity, address their sensitivity to acidic conditions and high heavy metal concentrations, and mitigate the risk of secondary pollution from excessive carbon sources. This study underscores the necessity for innovative and sustainable SRB-based bioremediation strategies that integrate multiple techniques to address the complex issue of heavy metal soil contamination. Such advancements are crucial for promoting green mining practices and environmental restoration.

[Effect of compatibility of Corni Fructus before and after wine-processing with Astragali Radix on plasma metabolomics in diabetic nephropathy rats based on UHPLC-Q-TOF-MS/MS].

Based on the processing and compatibility, this study explored the effects of components in Corni Fructus(CF) and Astragali Radix(AR) on plasma metabolomics in diabetic nephropathy rats. SD rats were randomly divided into four groups and diabetic nephropathy rat model was induced by high-fat diet combined with 30 mg·kg~(-1) streptozotocin(STZ). Histopathological observations of kidney tissue sections of rats in each group were conducted using HE, PAS, and Masson staining. Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) metabolomics method was employed to investigate the effects of CF before and after wine-processing combined with AR-related components on plasma metabolites in diabetic nephropathy rats. After drug treatment, kidney tissue damage and interstitial collagen fiber deposition area in diabetic nephropathy rats were improved to varying degrees(P<0.001). The detection results of plasma metabolomics showed that 71 biomarkers related to the pathogenesis of diabetic nephropathy were identified in diseased rats, mainly involving linoleic acid metabolism, caffeine metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, phenylalanine metabolism, retinol metabolism, and ether lipid metabolism. After drug intervention, 26 of them were significantly downregulated, with better efficacy observed in precision processed herb-pair group(P-CG_5). This study elucidated from the perspective of plasma metabolomics that P-CG_5 could improve metabolic disorders in diabetic nephropathy through pathways such as phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and caffeine metabolism, providing theoretical support and experimental basis for the clinical application of CF and AR compatibility in traditional Chinese medicine.

Molecular Engineering of Perylene Diimide Polymers with a Robust Built-in Electric Field for Enhanced Solar-Driven Water Splitting.

The built-in electric field of the polymer semiconductors could be regulated by the dipole moment of its building blocks, thereby promoting the separation of photogenerated carriers and achieving efficient solar-driven water splitting. Herein, three perylene diimide (PDI) polymers, namely oPDI, mPDI and pPDI, are synthesized with different phenylenediamine linkers. Notably, the energy level structure, light-harvesting efficiency, and photogenerated carrier separation and migration of polymers are regulated by the orientation of PDI unit. Among them, oPDI enables a large dipole moment and robust built-in electric field, resulting in enhanced solar-driven water splitting performance. Under simulated sunlight irradiation, oPDI exhibits the highest photocurrent of 115.1 µA cm-2 for photoelectrochemical oxygen evolution, which is 11.5 times that of mPDI, 26.8 times that of pPDI and 104.6 times that of its counterparts PDI monomer at the same conditions. This work provides a strategy for designing polymers by regulating the orientation of structural units to construct efficient solar energy conversion systems.

Chiral hybrid waveguide-plasmon resonances.

We investigate the chiroptical responses of the hybrid systems consisting of metal-insulator-metal (MIM) gammadion arrays on top of a dielectric slab waveguide. We demonstrate that both the transverse magnetic (TM) and transverse electric (TE) waveguide modes could be coupled to the antisymmetric localized surface plasmon resonances (LSPRs) of the individual MIM-gammadions, leading to the formation of narrow hybrid waveguide-plasmon resonances (WPRs), of which the TM-WPR is less dependent while the TE-WPR is highly dependent on the handedness of the incident light. Associated with the excitation of the TE-WPRs, strong negative and positive circular dichroism (CD) peaks with high quality factors could be obtained on the short-wavelength and long-wavelength side of the LSPRs of the MIM-gammadion, respectively. Moreover, we show that the variation on either the lattice period or slab waveguide thickness allows for easily tuning the TE-WPRs based CD peaks over a relative wide spectral range. Our proposed hybrid system provides tunable and strong CD responses with narrow linewidth, which may have applications in chiral selective imaging, chiral plasmonic bio-sensing and spectroscopy.

Analyte-triggered in situ "off-on" of Tyndall effect for smartphone-based quantitative nanosensing of Ag+ ions.

This work describes two new colorimetric methods for smartphone-based point-of-care nanosensing of toxic Ag+ ions. They were based on the analyte-triggered in situ "off-on" of Tyndall effect (TE) of non-plasmonic colloid or plasmonic metal nanoprobes. The first TE-inspired assay (TEA) focused on the initial analytical application of precipitation reactions where a non-plasmonic AgCl colloid could be formed once mixing the analyte with a NaCl solution. Such AgCl colloid displayed strong visual TE signals after their irradiation by a laser pointer pen, which unexpectedly achieved a detection limit of ~ 400 nM. The second TEA was further designed to reduce the limit down to ~ 78 nM using the analyte's oxidizability towards 3,3',5,5'-tetramethylbenzidine molecules. The redox reaction could create positively charged products that could make negatively charged plasmonic gold nanoparticles aggregate through electrostatic interactions to remarkably amplify their TE responses. Both limits were lower than the minimum allowable Ag+ level (~ 460 nM) in drinking water issued by the World Health Organization. The satisfactory recovery results for detecting Ag+ ions in river, pond, tap, and drinking water additionally demonstrated good selectivity, accuracy and practicality of the proposed methods for potential point-of-need uses in environmental analysis, public health, water safety, etc.

An aptamer array for discriminating tetracycline antibiotics based on binding-enhanced intrinsic fluorescence.

Tetracyclines are a class of antibiotics with a similar four-ringed structure. Due to this structural similarity, they are not easily differentiated from each other. We recently selected aptamers using oxytetracycline as a target and focused on an aptamer named OTC5, which has similar affinities for oxytetracycline (OTC), tetracycline (TC), and doxycycline (DOX). Tetracyclines exhibit an intrinsic fluorescence that is enhanced upon aptamer binding, allowing convenient binding assays and label-free detection. In this study, we analyzed the top 100 sequences from the previous selection library. Three other sequences were found to differentiate between different tetracyclines (OTC, DOX, and TC) by the selective enhancement of their intrinsic fluorescence. Among them, the OTC43 aptamer was more selective for OTC with a limit of detection (LOD) of 0.7 nM OTC, OTC22 was more selective for DOX (LOD 0.4 nM), and OTC2 was more selective for TC (0.3 nM). Using these three aptamers to form a sensor array, principal component analysis was able to discriminate between the three tetracyclines from each other and from the other molecules. This group of aptamers could be useful as probes for the detection of tetracycline antibiotics.

Induction of clastogenesis and gene mutations by carbamazepine (at its therapeutically effective serum levels) in mammalian cells and the dependence on human CYP2B6 enzyme activity.

Carbamazepine (CBZ, an antiepileptic) is metabolized by multiple CYP enzymes to its epoxide and hydroxides; however, whether it is genotoxic remains unclear. In this study, molecular docking (CBZ to CYPs) and cytogenotoxic toxicity assays were employed to investigate the activation of CBZ for mutagenic effects, in various mammalian cell models. Docking results indicated that CBZ was valid as a substrate of human CYP2B6 and 2E1, while not for CYP1A1, 1A2, 1B1 or 3A4. In the Chinese hamster (V79) cell line and its derivatives genetically engineered for the expression of human CYP1A1, 1A2, 1B1, 2E1 or 3A4 CBZ (2.5 ~ 40 µM) did not induce micronucleus, while in human CYP2B6-expressing cells CBZ significantly induced micronucleus formation. In a human hepatoma C3A cell line, which endogenously expressed CYP2B6 twofold higher than in HepG2 cells, CBZ induced micronucleus potently, which was blocked by 1-aminobenzotriazole (inhibitor of CYPs) and ticlopidine (specific CYP2B6 inhibitor). In HepG2 cells CBZ did not induce micronucleus; however, pretreatment of the cells with CICTO (CYP2B6 inducer) led to micronucleus formation by CBZ, while rifampicin (CYP3A4 inducer) or PCB126 (CYP1A inducer) did not change the negative results. Immunofluorescent assay showed that CBZ selectively induced centromere-free micronucleus. Moreover, CBZ induced double-strand DNA breaks (γ-H2AX elevation, by Western blot) and PIG-A gene mutations (by flowcytometry) in C3A (threshold being 5 µM, lower than its therapeutic serum concentrations, 17 ~ 51 µM), with no effects in HepG2 cells. Clearly, CBZ may induce clastogenesis and gene mutations at its therapeutic concentrations, human CYP2B6 being a major activating enzyme.

Novel mechanisms of cadmium tolerance and Cd-induced fungal stress in wheat: Transcriptomic and metagenomic insights.

Although several studies on the effects of cadmium (Cd) on wheat have been reported, the gene expression profiles of different wheat tissues in response to gradient concentrations of Cd, and whether soil microorganisms are involved in the damage to wheat remain to be discovered. To gain further insight into the molecular mechanisms of Cd-resistance in wheat, we sowed bread wheat (Triticum aestivum) in artificially Cd-contaminated soil and investigated the transcriptomic response of the wheat roots, stems, and leaves to gradient concentrations of Cd, as well as the alteration of the soil microbiome. Results indicated that the root bioaccumulation factors increased with Cd when concentrations were < 10 mg/kg, but at even higher concentrations, the bioaccumulation factors decreased, which is consistent with the overexpression of metal transporters and other genes related to Cd tolerance. In the Cd-contaminated soil, the abundance of fungal pathogens increased, and the antimicrobial response in wheat root was observed. Most of the differentially expressed genes (DEGs) of wheat changed significantly when the Cd concentration increased above 10 mg/kg, and the transcriptional response is much greater in roots than in stems and leaves. The DEGs are mainly involved in Cd transport and chelation, antioxidative stress, antimicrobial responses, and growth regulation. COPT3 and ZnT1 were identified for the first time as the major transporters responding to Cd in wheat. Overexpression of the nicotianamine synthase and pectinesterase genes suggested that nicotianamine and pectin are the key chelators in Cd detoxification. endochitinase, chitinase, and snakin2 were involved in the anti-fungal stress caused by Cd-induced cell damage. Several phytohormone-related DEGs are involved in the root's growth and repair. Overall, this study presents the novel Cd tolerance mechanisms in wheat and the changes in soil fungal pathogens that increase plant damage.

Mechanistic Investigation of Enhanced Catalytic Selectivity toward Alcohol Oxidation with Ce Oxysulfate Clusters.

Ceria-based materials have been highly desired in photocatalytic reactions due to their redox properties and strong oxygen storage and transfer ability. Herein, we report the structures of one CeCe70 oxysulfate cluster and four MCe70 clusters (M = Cu, Ni, Co, and Fe) with the same Ce70 core. As noted, single-crystal X-ray diffraction confirmed the structures of CeCe70 and the MCe70 series, while Raman spectroscopy indicated an increase in oxygen defects upon the introduction of Cu and Fe ions. The clusters catalyzed the oxidation of 4-methoxybenzyl alcohol under ultraviolet light. CuCe70 and FeCe70 exhibited enhanced reactivity compared to CeCe70 and improved aldehyde selectivity compared to control experiments. In comparison with their homogeneous congeners, the CeCe70/MCe70 clusters altered the location of radical generation from the bulk solution to the clusters' surfaces. Mechanistic studies highlight the role of oxygen defects and specific transition metal introduction for efficient photocatalysis. The mechanistic pathway in this study provides insight into how to select or design a highly selective catalyst for photocatalysis.

Label-free and Dye-free Fluorescent Sensing of Tetracyclines Using a Capture-Selected DNA Aptamer.

Tetracyclines are a group of important antibiotics with a common four-ring scaffold. While most tetracyclines are currently used only in animals, their leaching into the environment and residues in food have caused health concerns. Aptamers are an attractive way to detect tetracyclines, and all previously reported aptamers for tetracyclines were obtained by immobilizing target molecules. In this work, we selected a few DNA aptamers by immobilizing the DNA library using oxytetracycline as the target. We obtained new aptamers with no overlapping sequences compared to the previously reported ones, and a representative sequence named OTC5 had a dissociation constant of 147 nM measured by isothermal titration calorimetry. Similar binding affinities were also observed with tetracycline and doxycycline. Because tetracyclines are fluorescent and their fluorescence intensity was enhanced by binding to the aptamers, a label-free and dye-free fluorescent biosensor was developed with a detection limit of 25 nM oxytetracycline. The sensor was able to detect targets in milk after extraction. Fluorescence polarization measurement showed that this aptamer is insensitive to sodium concentration but requires magnesium. Finally, a strand-displacement biosensor was designed, and it has a detection limit of 1.2 µM oxytetracycline.

Geological and climatic influences on population differentiation of the Phrynocephalus vlangalii species complex (Sauria: Agamidae) in the northern Qinghai-Tibet Plateau.

Extremely heterogeneous topography and complex paleoclimatic history of the Qinghai-Tibet Plateau (QTP) have a key role in promoting genetic divergence among populations and lineage/species formation. Here, we sequenced one nuclear and three mitochondrial markers of 532 individuals from the entire range of the Phrynocephalus vlangalii species complex including two species, P. putjatai and P. vlangalii, endemic to the northern QTP. We integrated multilocus phylogeny, demographic analysis and geographic barrier detection to evaluate the population structure and dynamics. We found a new mitochondrial clade (PV-I) in the Gonghe County population of P. vlangalii, partial mitochondrial DNA replacement within P. vlangalii and complete mitochondrial DNA replacement between P. putjatai and P. vlangalii. Neutrality test, mismatch distribution analysis and Extended Bayesian Skyline Plot (EBSP) analysis all supported a significant expansion of the Qaidam Basin population of P. vlangalii (PV-II-2) from 0.091 to 0.026 Ma after Penultimate Glaciation. The uplift of the Arjin and Anyemanqen Mountains during the Kunhuang Movement (∼1.2 Ma) split populations of P. vlangalii in Akesai, Qaidam Basin and source of the Yellow River. The uplift of the Elashan Mountains during the second phase of the Qingzang Movement (∼2.5 Ma) contributed to the divergence of the Gonghe County population of P. vlangalii from other conspecific populations. The third phase of the Qingzang Movement (∼1.7 Ma) contributed to the divergence of the Xinghai population of P. vlangalii from P. putjatai and to the divergence of the northern populations of P. putjatai from the southern conspecific populations. Our data support the idea that the geological and climatic changes following the orogeny of the QTP may have promoted population differentiation and shaped the current population patterns of the P. vlangalii species complex in the northeastern QTP.

Enhanced Photoelectrochemical Water Splitting of Black Silicon Photoanode with pH-Dependent Copper-Bipyridine Catalysts.

Since the water oxidation half-reaction requires the transfer of multi-electrons and the formation of O-O bond, it's crucial to investigate the catalytic behaviours of semiconductor photoanodes. In this work, a bio-inspired copper-bipyridine catalyst of Cu(dcbpy) is decorated on the nanoporous Si photoanode (black Si, b-Si). Under AM1.5G illumination, the b-Si/Cu(dcbpy) photoanode exhibits a high photocurrent density of 6.31 mA cm-2 at 1.5 VRHE at pH 11.0, which is dramatically improved from the b-Si photoanode (1.03 mA cm-2 ) and f-Si photoanode (0.0087 mA cm-2 ). Mechanism studies demonstrate that b-Si/Cu(dcbpy) has improved light-harvesting, interfacial charge-transfer, and surface area for water splitting. More interestingly, b-Si/Cu(dcbpy) exhibits a pH-dependent water oxidation behaviour with a minimum Tafel slope of 241 mV/dec and the lowest overpotential of 0.19 V at pH 11.0, which is due to the monomer/dimer equilibrium of copper catalyst. At pH ∼11, the formation of dimeric hydroxyl-complex could form O-O bond through a redox isomerization (RI) mechanism, which decreases the required potential for water oxidation. This in-depth understanding of pH-dependent water oxidation catalyst brings insights into the design of dimer water oxidation catalysts and efficient photoanodes for solar energy conversion.