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Synthetic lethality has recently emerged as a new approach for the treatment of mutated genes that were previously considered undruggable. Targeting methionine adenosyltransferase 2A (MAT2A) in cancers with deletion of the methylthioadenosine phosphorylase (MTAP) gene leads to synthetic lethality and thus has attracted significant interest in the field of precise anticancer drug development. Herein, we report the discovery of a series of novel MAT2A inhibitors featuring a pyrazolo[3,4-c]quinolin-4-one skeleton based on structure-based drug design. Further optimization led to compound 39, which has a high potency for inhibiting MAT2A and a remarkable selectivity for MTAP-deleted cancer cell lines. Compound 39has a favorable pharmacokinetic profile with high plasma exposure and oral bioavailability, and it exhibits significant efficacy in xenograft MTAP-depleted models. Moreover, 39demonstrates excellent brain exposure with a Kpuuof 0.64 in rats.

Advanced oxidation process (AOP) wet scrubber is a powerful and clean technology for organic pollutant treatment but still presents great challenges in removing the highly toxic and hydrophobic volatile organic compounds (VOCs). Herein, we elaborately designed a bifunctional cobalt sulfide (CoS2)/activated carbon (AC) catalyst to activate peroxymonosulfate (PMS) for efficient toxic VOC removal in an AOP wet scrubber. By combining the excellent VOC adsorption capacity of AC with the highly efficient PMS activation activity of CoS2, CoS2/AC can rapidly capture VOCs from the gas phase to proceed with the SO4•–and HO•radical-induced oxidation reaction. More than 90% of aromatic VOCs were removed over a wide pH range (3–11) with low Co ion leaching (0.19 mg/L). The electron-rich sulfur vacancies and low-valence Co species were the main active sites for PMS activation. SO4•–was mainly responsible for the initial oxidation of VOCs, while HO•and O2acted in the subsequent ring-opening and mineralization processes of intermediates. No gaseous intermediates from VOC oxidation were detected, and the highly toxic liquid intermediates like benzene were also greatly decreased, thus effectively reducing the health toxicity associated with byproduct emissions. This work provided a comprehensive understanding of the deep oxidation of VOCs via AOP wet scrubber, significantly accelerating its application in environmental remediation.

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of different variants of concerns with immune evasion that have been prevalent over the past three years. Nanobodies, the functional variable regions of camelid heavy-chain-only antibodies, have garnered interest in developing neutralizing antibodies due to their smaller size, structural stability, ease of production, high affinity, and low immunogenicity, among other characteristics. In this work, we describe an integrated proteomics platform for the high-throughput screening of nanobodies against different SARS-CoV-2 spike variants. To demonstrate this platform, we immunized a camel with subunit 1 (S1) of the wild-type spike protein and constructed a nanobody phage library. The binding and neutralizing activities of the nanobodies against 72 spike variants were then measured, resulting in the identification of two nanobodies (C-282 and C-39) with broad neutralizing activity against six non-Omicron variants (D614G, Alpha, Beta, Gamma, Delta, Kappa) and five Omicron variants (BA.1–5). Their neutralizing capability was validated using in vitro pseudovirus-based neutralization assays. All these results demonstrate the utility of our proteomics platform to identify new nanobodies with broad neutralizing capability and to develop a treatment for patients with SARS-CoV-2 variant infection in the future.

A hybrid photothermal catalytic system, which combines both the photochemical (light) and thermal (heat) activation pathways over a bifunctional catalyst, has demonstrated remarkable levels of reaction activity and selectivity when compared with individual photocatalysis and thermocatalysis. However, the complex nature of the hybrid system, coupled with the synergy between photocatalysis and thermocatalysis, has made it challenging to understand (and thus manipulate) the role of individual stimuli (light/heat) and catalyst surface processes. In this perspective, a systematic classification for different (complicated) photothermal catalysis reaction systems is provided. We evaluate the singular catalytic characteristics of each category, together with the competence of light-heat dual activation in overcoming the well-defined limitations in photocatalysis and thermocatalysis, mainly in the scope of C1 chemistry. Notably, the interplay and cooperation among heat and/or light-induced effects can be engineered to greatly extend the capability of chemical transformation (i.e., product selectivity and reactivity) via the well-established photo-thermo cascade reaction. Finally, we provide critical insights into the catalyst development and reactor design for high-performance light-heat-coupled catalytic systems.

Non-volatile memory devices have become crucial components in emerging fields like integrated circuits and quantum computing. However, their cryogenic use remains a challenge today. Here we fabricated ferroelectric domain wall memory devices using an X-cut LiNbO3 (LNO) thin film on silicon, and their on/off currents after the creation and erasure of conducting domain walls between two antiparallel/parallel domains were investigated at low temperatures. The readout current is sufficiently larger than $10~\mu \text{A}$ , though the domain wall current decreases nearly by a half upon cooling of the device from 300 to 120 K. The cryogenic memory has a large on/off ratio ( $10^{{4}}{)}$ , long retention time (>10 years) and high endurance cycles ( $10^{{9}}{)}$ , and can be applied at extremely harsh environments.

Arctic navigability is crucial to the global economy and landscape, while there is an omission in understanding how Arctic navigability changes as a function of 1.5 °C of the Paris Agreement. This study investigated the impact of 1.5 °C global warming above the preindustrial level on sea ice conditions and accessibility of the Northern Sea Route (NSR) and Northwest Passage (NWP) with the Polar Operational Limit Assessment Risk Indexing System and new risk demarcation criteria. The Arctic is colder on the Canadian side than on the European side under 1.5 °C warming. Sea ice is mostly less than three years old, and the younger, thinner and less concentrated ice is mainly in the seas along the NSR. Ships above Polar Class (PC) 6 might be unimpeded along two passages all the year. Besides, the NSR and NWP have great potential for PC6 ships in October–December, while it is only the NSR for PC7 ships. Caution is still required when navigating the western East Siberian Sea, its surrounding straits, and the Parry Channel. These changes in hydrological conditions are important for global shipping, and this work is helpful for supporting coordinated international decision-making.

Ferroelectric domain walls, agile nanoscale interfaces of polar order, can be selectively controlled by electric fields for their position, conformation, and function, which is ultimately the key to realizing novel low-energy memory and computing structures. LiNbO3single-crystal domain wall memory has the advantages of high operational speed, high integration density, and virtually unlimited endurance cycles, appearing as a good solution for the next generation of highly miniaturized low-energy memories. However, the etching process poses significant challenges in the nanofabrication and high-density integration of LiNbO3domain-wall memories. Here, we employed a hybrid etching technique to achieve smooth sidewalls with a 90° inclined angle, leading to a 24% reduction in the coercive field and a 2.5-fold increase in the linear domain wall current density with a retention time of more than 106seconds and endurance of over 105writing cycles. Combined with the results of X-ray diffraction patterns and X-ray photoelectric spectra, it is concluded that the excellent electrical performance is related to the formation of an oxygen-deficient LiNbO3–xlayer on the sidewall surface during the wet chemical etching process, which is a conductive layer that reduces the thickness of the “dead” layer between the side electrodes and the LiNbO3cell and rectifies the diode-like wall currents with an onset voltage reduced from 1.23 to 0.28 V. These results prove the high-density integration of ferroelectric domain-wall memories at the nanoscale and provide a new strategy applicable to the development of LiNbO3photonic devices.

Organophosphate flame retardants (OPFRs) are emerging organic pollutants in PM2.5, which have caused significant public health concerns in recent years, given their potential carcinogenic and neurotoxic effects. However, studies on the sources, occurrence, and health risk assessment of PM2.5-bound OPFRs in Hong Kong are lacking. To address this knowledge gap, we characterized 13 OPFRs in one-year PM2.5samples using gas chromatography–atmospheric pressure chemical ionization tandem mass spectrometry. Our findings showed that OPFRs were present at a median concentration of 4978 pg m–3(ranging from 1924 to 8481 pg m–3), with chlorinated OPFRs dominating and accounting for 82.7% of the total OPFRs. Using characteristic source markers and positive matrix factorization, we identified one secondary formation and five primary sources of OPFRs. Over 94.0% of PM2.5-bound OPFRs in Hong Kong were primarily emitted, with plastic processing and waste disposal being the leading source (61.0%), followed by marine vessels (14.1%). The contributions of these two sources to OPFRs were more pronounced on days influenced by local pollution emissions (91.9%) than on days affected by regional pollution (44.2%). Our assessment of health risks associated with human exposure to PM2.5-bound OPFRs indicated a low-risk level. However, further source-specific health risk assessment revealed relatively high noncarcinogenic and carcinogenic risks from chlorinated OPFRs emitted from plastic processing and waste disposal, suggesting a need for more stringent emission control of OPFRs from these sources in Hong Kong.

Abstract: In the present work, a potential solid-phase extraction (SPE) material based on graphene anchored with platinum nanoparticles (Pt-Graphene) was prepared and characterized by scanning electron micrographs and transmission electron micrograph. The carbamates residues in fish were enriched by SPE filled with Pt-Graphene and detected by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). The proposed extraction protocol exhibited satisfactory recoveries (76.5–115.6%), low limit of quantitation values in μg kg−1level, and good precision for the studied ten carbamates. These results demonstrated the feasibility of the proposed protocol. The developed Pt-Graphene nanoparticles showed excellent performance for extracting analytes at trace levels, indicating that it could be used as a potential SPE sorbent in food residue analysis. Graphical abstract:

To evaluate the therapeutic effect of Saccharomyces boulardiisupplementation on jaundice in premature infants undergoing phototherapy.

Direct functionalization of methane selectively to value-added chemicals is still one of the main challenges in modern science. Acetic acid is an important industrial chemical produced nowadays by expensive and environmentally unfriendly carbonylation of methanol using homogeneous catalysts. Here, we report a new photocatalytic reaction route to synthesize acetic acid from CH4and CO at room temperature using water as the sole external oxygen source. The optimized photocatalyst consists of a TiO2support and ammonium phosphotungstic polyoxometalate (NPW) clusters anchored with isolated Pt single atoms (Pt1). It enables a stable synthesis of 5.7 mmol·L–1acetic acid solution in 60 h with the selectivity over 90% and 66% to acetic acid on liquid-phase and carbon basis, respectively, with the production of 99 mol of acetic acid per mol of Pt. Combined isotopic and in situspectroscopy investigation suggests that synthesis of acetic acid proceeds via a photocatalytic oxidative carbonylation of methane over the Pt1sites, with the methane activation facilitated by water-derived hydroxyl radicals.

High-density domain wall memory based on crossbar architecture is a strong contender among next-generation high performance versatile memories due to its ultra-fast operation speed and excellent size scalability. Herein, we report 4 $\times $ 4 domain wall crossbar memory arrays fabricated on a LiNbO3 single crystal. Reversible creation and erasure of conducting domain walls between two antiparallel/parallel domains at bipolar write voltages enable the storage of digital “0” and “1” information. At the crosspoint of each word and bit lines, the memory cell can be accurately accessed, programmed and erased. The diode-like rectification of readout currents exhibited by all memory cells can inhibit read and write crosstalk. The electrical testing results in the crossbar memory array demonstrated the good stability of on/off currents and good uniformity of operating voltages, which can be reflected by the fact that the distribution of the coercive voltages is within 2.9 V and the “on”/ “off” current ratio is around 100 at a reading voltage of 3 V. Good data retention and fatigue resistance are also exhibited, making it possible to integrate domain wall random access memories in high density and reliability.

The uncontrollable formation of polymorphous Li deposits, e.g., whiskers, mosses, or dendrites resulting from nonuniform interfacial current distribution and internal stress release in the upward direction on the conventional current collector (e.g., Cu foil) of Li metal rechargeable batteries with a lithium-metal-free negatrode (LMFRBs), leads to rapid performance degradation or serious safety problems. The 3D carbon nanotubes (CNTs) skeleton has been proven to effectively reduce the current density and eliminate the internal accumulated stress. However, remarkable electrolyte decomposition, inherent Li source consumption due to repeated SEI formation, and Li+intercalation in CNTs limit the application of 3D CNTs skeleton. Thus, it is necessary to avoid the side effects of the 3D CNTs skeleton and retain uniform interfacial current distribution and stress mitigation. In this work, we integrate the CNTs network with a soft functional polymer polyvinylidene fluoride (PVDF) to form a relatively dense coating layer on Cu foil, which can shield the contact between the internal surface of the 3D CNTs framework and the electrolyte. Simultaneously, the Li–F-rich SEI resulting from the partial reduction of PVDF with deposited Li and the soft nature of the coating layer release the accumulation of internal stress in the horizontal direction, resulting in mosses/whisker-free Li deposition. Thus, improved Li deposition/dissolution and stable cycling performance of the LMFRBs can be achieved.

A Ru(Ⅲ)-catalyzed annulation reaction of 2-aminoaromatic aldehydes (ketones) and isoxazoles to afford diverse 3-cyanoquinolines has been developed. Notably, isoxazole acted as a cyclization reagent and nontoxic cyano source viaN-O bond cleavage and fragmentation. Variously substituted (especially 6- or 7-substituted) quinolines could be easily afforded. This procedure features wide functional group compatibility, efficiency and avoiding toxic cyano source. Meanwhile, this protocol could be successfully applied to scale-up synthesis. Further chemical transformations of 3-cyanoquinoline could give some valuable skeletons, demonstrating its potential in synthetic application

A rhodium-catalyzed cyclization of azobenzenes and vinylene carbonate via C–H bond activation to construct indazolo[2,3-a]quinolines has been developed. This protocol offers an efficient method for synthesis of the titled products in good yields with broad functional group tolerance. In this reaction, three C–C bonds and C–N bond are formed in one pot, and vinylene carbonate (VC) acts as C1 and C2 synthons as well as “vinylene transfer” agent and acylation reagent in the construction of target-fused heterocycles. Moreover, the products exhibit favorable fluorescence properties, which indicate their potential application as fluorescent materials and biosensors.

p-Phenylenediamines (PPDs) have been extensively used in the rubber industry and found to be pervasive in various environmental compartments for decades, while their transformation products and associated ecological and human health risks remain largely unknown. Herein, we developed and implemented a mass spectrometry-based platform combined with self-synthesized standards for the investigation of rubber-derived quinones formed from PPD antioxidants. Our results demonstrated that five quinones are ubiquitously present in urban runoff, roadside soils, and air particles. All of the identified sources are closely related to mankind’s activities. Among the identified quinones, N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone has been recently found to be highly toxic, causing acute mortality of coho salmon in the Pacific Northwest. Ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry was then applied for quantification of the five quinones and their corresponding PPD antioxidants. The results revealed interesting distinct distribution and concentration patterns of PPD-derived quinones in different environmental matrices. Daily intake rates of these quinones in a compact city of Hong Kong were estimated to be varied from 1.08 ng/(kg·day) for adults to 7.30 ng/(kg·day) for children, which were higher than the exposure levels of their parent compounds. Considering the prevalence of the use of rubber products, the outcome of this study strongly suggests for additional toxicological studies to investigate potential ecological and human health risks of the newly discovered quinones.

The heterogeneity of programmed death-ligand 1 (PD-L1) status between core needle biopsies (CNBs) from one tumor has not been well studied before. The current study attempts to find out the best index using multiple core biopsies from one tumor which can better reflect the actual PD-L1 status. Random CNB was performed in surgical specimens from 170 consecutive non–small cell lung cancer samples. Fifty-one cases (41 cases with PD-L1 positive and 10 cases with PD-L1 negative) and 216 matched CNBs were analyzed by DAKO 22C3 PharmDx Link 48 Autostainer. The PD-L1 status was compared between the surgical specimens and matched CNBs. Heterogeneity of PD-L1 status between CNBs from one tumor was observed in 56% of PD-L1 positive cases. Different tumor proportion score (TPS) statistical forms with regard to the highest, mean, median, weighted average TPS, as well as TPS showed by the longest biopsy specimen and the biopsy with most tumor volume were compared. At a cut-off of 1%, the concordance rates were 94.1%, 88.2%, 90.2%, 86.3%, 86.3%, and 86.3%; At a cut-off of 50%, the concordance rates were 92.2%, 86.3%, 84.3%, 82.4%, 82.4%, and 86.3%, respectively. The CNB with the highest TPS can best represent PD-L1 status estimated by whole surgical specimen. The highest TPS among the multiple biopsies is a robust evaluation of the PD-L1 status, but not mean TPS, at the 1% and 50% cut-offs.

Simultaneous upgrading of biomass derivatives on highly efficient nonprecious metal-electrocatalysts is still an unprecedented challenge. We propose an electrocatalytic reductive amination and simultaneous oxidation (ERAO) route to convert biomass-derived 5-hydroxymethylfurfural (HMF) into valuable 2-hydroxymethyl-5-(ethanolamine methyl)furan (HEMF) at the cathode side and 2,5-furandicarboxylic acid (FDCA) at the anode. Accordingly, the cathode and anode electrode materials of the ERAO electrolyzer are titanium-based metal–organic framework (Ti-MOF) cubes and NiCoFe-LDHs nanosheets, respectively. The overall ERAO shows very good performance with ∼68% conversion of HMF after 6 h reaction, which is closely related to the exposed N–Ti–O active center from Ti-MOF and porous structure in providing extra access to the internal sites. The good stability of these catalysts after ERAO was further investigated. This work provides a sustainable route for biomass upgrading using the highly efficient nonprecious metal electrocatalysts.

High-value reclamation of metal-polluted plants involved in phytoremediation is a big challenge. In this study, nitrogen-doped nanoporous carbon with large specific area of 2359.1 m2 g−1is facilely fabricated from metal-polluted miscanthus waste for efficient energy storage. The synergistic effect of KOH, urea and ammonia solution greatly improve the nitrogen quantity and surface area of the synthesized carbon. Electrodes fabricated with this carbon exhibit the excellent capacitance performance of 340.2 F g−1at 0.5 A g−1and a low combined resistance of 0.116 Ω, which are competitive with most of previously reported carbon-based electrodes. In addition, the as-obtained carbon electrode shows a high specific capacitance retention of over 99.6% even after 5000 cycles. Furthermore, the symmetric supercapacitor fabricated using the synthesized carbon achieves a superior energy density of 25.3 Wh kg−1(at 400 W kg−1) in 1 mol L−1Na2SO4aqueous solution. This work provides an efficient route to upcycle metal-polluted plant waste for supercapacitor applications.

An integrated quantitative proteomics strategy to investigate the anti-inflammation effect of celastrol in a rat macrophage cell line against the LPS-induced acute response. The stable-isotopic based non-targeted quantitative profiling was performed to identify key regulatory proteins of celastrol response to LPS challenge, the dynamic changes of candidate proteins were then monitored by PRM quantitation and qPCR assay at corresponding time points to reveal the dual anti-inflammatory mechanisms of Celastrol against the LPS-induced acute inflammation.

To help optimize the spacecraft design and reduce the risk of spacecraft mission failure, a new approach to assess the survivability of spacecraft in orbit is presented here, including the following three steps: 1) Sensitivity Analysis of spacecraft. A new sensitivity analysis method, a ray method based on virtual outer wall, is presented here. Using rays to simulate the debris cloud can effectively address the component shadowing issues. 2) Component Vulnerability analysis of spacecraft. A function “Component functional reduction degree – Component physical damage degree” is provided here to clearly describe the component functional reduction. 3) System-level Survivability Assessment of spacecraft. A new method based on expert knowledge reasoning, instead of traditional artificial failure tree method, is presented here to greatly improve the efficiency and accuracy of calculation.

The conductive metal-organic frameworks (MOFs) are suggested as the ideal electrocatalysts for hydrogen evolution reaction (HER) because of the high utilization of metal atoms. Rational design and facile synthesis of MOFs with large specific surface area, proper metals as center, and tunable chemical components is still full of challenges. Herein, we report the facile synthesis three types of porous MOFs by regulating metal center using benzene-1,3,5-tricarboxylic acid (H 3 BTC) as organic ligand and have successfully synthesized the rhombic octahedral Cu-BTC, rod-shaped Co-BTC and spherical Ni-BTC materials with large specific surface area ranged in 350-500 m2 g−1. These as-prepared MOFs materials exhibit high performance of HER in 0.5 M H 2 SO 4. Ni-BTC material exhibits the lowest overpotential of 53 mV at 10 mA cm-2 and the smallest Tafel slope of 62 mV dec−1 than those of Cu-BTC (270 mV, 155 mV dec−1) and Co-BTC (123 mV, 100 mV dec−1), which are much superior to these previously reported MOFs catalysts. In addition, the fast catalytic kinetic of Ni-BTC was confirmed by the smaller charge transfer resistance (Rct) value of 0.9 Ω and larger electrochemical active surface area (ECSA) of 35.5 cm2 than those of Cu-BTC (8.2 Ω, 22.5 cm2) and Co-BTC (1.9 Ω, 27.7 cm2). Because of the structural advantage and large ECSA, the turnover frequency (TOF) value of Ni-BTC reaches up to 0.041 s−1 at 120 mV overpotential, which is 20.5 and 2.6 times greater than that of Cu-BTC (0.002 s−1) and Co-BTC (0.016 s−1). Besides, these three types of MOFs exhibited excellent durability over 12 h. This study unfolds diverse insights into the design and facile synthesis of MOFs for electrochemical energy conversion system. [ABSTRACT FROM AUTHOR]

Recent advancements on electrochemical conversion of methane (ECM) to various chemicals based on surface/interface chemistry are summarized. The renewable-energy-driven ECM shows promise to bridge the gap in the artificial carbon cycle.

A switching-type power converter providing an accurate and stable switching output voltage against line/load variations and power supply ripple is mostly complicated in system-on-chip power management integrated circuits (PMICs) within a limited occupation area. Here we fabricated domain wall (DW) nanodevices using an X-cut LiNbO3thin film on silicon. The domain switching event occurs after a delay time predicted by Merz’s law under the applied voltage. But the output current is irrespective of the applied voltage and can be adjusted by conducting wall width as well as input resistance in the circuit. The regulating currents appear repetitively across the volatile interfacial domains between the nanodevice and electrode under intermittently applied voltages. A wall-current-limited domain switching model is developed to explain the phenomenon. The multifunctional DW nanodevices with smaller occupation areas can serve as compact low-dropout regulators in PMICs, time-domain delayers in energy-efficient neural network systems, and on-chip electrostatic discharge protection besides nonvolatile memories and selectors.

Cataract patients look forwards to fewer postoperative complications and higher vision quality after surgery. However, the current intraocular lens (IOL) implanted after cataract surgery neither can adjust focal length in response to ciliary muscle contraction as natural lens nor have the ability to prevent postoperative complications. Herein, a thermosensitve Poloxamer based hybrid hydrogel with antibacterial anti-inflammatory and photothermal functional elements doping was designed and used as injectable, in situ curable, and adjustable IOL (FHTAB IOL). The FHTAB IOL was composed of thermosensitve triblock-polymer F127DA and a small amount of HAMA, combined with BP NS, TA, and Ag NPs. FHTAB IOL can be injected into the empty lens capsule after cataract surgery via an injectable thermos-gel under NIR illumination and then be rapidly cured to form a full-size IOL under short-time blue light irradiation. The designed injectable FHTAB IOL possesses high transparency and transmittance, with a refractive index similar to the natural lens and adjustable properties. It was stabilized as a refractive medium without any leakage in the eye. In addition, the TA and Ag NPs loaded in the FHTAB IOL displayed significant antibacterial and anti-inflammatory effects in vitro and vivo. This study presents a potentially effective new strategy for the development of multifunctional adjustable IOLs.

Transarterial radioembolization (TARE) is a highly effective localized radionuclide therapy that has been successfully used to treat hepatocellular carcinoma (HCC). Extensive research has been conducted on the use of radioactive microspheres (MSs) in TARE, and the development of ideal radioactive MSs is crucial for clinical trials and patient treatment. This study presents the development of a radioactive MS for TARE of HCC. These MSs, referred to as 177Lu-MS@PLGA, consist of poly(lactic-co-glycolic acid) (PLGA) copolymer and radioactive silica MSs, labeled with 177Lu and then coated with PLGA. It has an extremely high level of radiostability. Cellular experiments have shown that it can cause DNA double-strand breaks, leading to cell death. In vivo radiostability of 177Lu-MS@PLGA is demonstrated by microSPECT/CT imaging. In addition, the antitumor study has shown that TARE of 177Lu-MS@PLGA can effectively restrain tumor growth without harmful side effects. Thus, 177Lu-MS@PLGA exhibits significant potential as a radioactive MS for the treatment of HCC.

Diagnosing, predicting disease outcome, and identifying effective treatment targets for virus-related cancers are lacking. Protein biomarkers have the potential to bridge the gap between prevention and treatment for these types of cancers. While it has been shown that certain antibodies against EBV proteins could be used to detect nasopharyngeal carcinoma (NPC), antibodies targeting are solely a tiny part of the about 80 proteins expressed by the EBV genome. Furthermore, it remains unclear what role other viruses play in NPC since many diseases are the result of multiple viral infections. For the first time, this study measured both IgA and IgG antibody responses against 646 viral proteins from 23 viruses in patients with NPC and control subjects using nucleic acid programmable protein arrays. Candidate seromarkers were then validated by ELISA using 1665 serum samples from three clinical cohorts. We demonstrate that the levels of five candidate seromarkers (EBV-BLLF3-IgA, EBV-BLRF2-IgA, EBV-BLRF2-IgG, EBV-BDLF1-IgA, EBV-BDLF1-IgG) in NPC patients were significantly elevated than controls. Additional examination revealed that NPC could be successfully diagnosed by combining the clinical biomarker EBNA1-IgA with the five anti-EBV antibodies. The sensitivity of the six-antibody signature at 95% specificity to diagnose NPC was comparable to the current clinically-approved biomarker combination, VCA-IgA and EBNA1-IgA. However, the recombinant antigens of the five antibodies are easier to produce and standardize compared to the native viral VCA proteins. This suggests the potential replacement of the traditional VCA-IgA assay with the 5-antibodies combination to screen and diagnose NPC. Additionally, we investigated the prognostic significance of these seromarkers titers in NPC. We showed that NPC patients with elevated BLLF3-IgA and BDLF1-IgA titers in their serum exhibited significantly poorer disease-free survival, suggesting the potential of these two seromarkers as prognostic indicators of NPC. These findings will help develop serological tests to detect and treat NPC in the future.

Alcohol consumption is one of the leading causes of death worldwide. Adolescence is a critical period of structural and functional maturation of the brain. Adolescent alcohol use can alter epigenetic modifications. However, little is known on the long-term effects of alcohol consumption during adolescence on RNA epigenetic modifications in brain. Herein, we systematically explored the long-term effects of alcohol exposure during adolescence on small RNA modifications in adult rat brain tissues by comprehensive liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. We totally detected 26 modifications in small RNA of brain tissues. Notably, we observed most of these modifications were decreased in brain tissues. These results suggest that alcohol exposure during adolescence may impose a long-lasting impact on RNA modifications in brain tissues. This is the first report that alcohol use during adolescence can alter RNA modifications in adult brain. Collectively, this study suggests a long-term adverse effects of alcohol consumption on brain from RNA epigenetics angle by comprehensive mass spectrometry analysis.

We systematically investigated the landscape of modifications in DNA and RNA molecules across multiple tissues in response to chronic sleep deprivation (CSD). Our study sheds light on the influence of CSD on epigenetic DNA and RNA modifications.

A climate transition towards warm–wet conditions in Northwest China has drawn much attention. With continuous climate change and universal glacier degradation, increasing water-related hazards and vulnerability have become one of the important problems facing the Tarim Basin. However, the impacts of the climate transition on streamflow abrupt change and extreme hydrological events were less discussed, especially in glacial basins. In the present study, the discharge datasets in four glacial basins of Tarim Basin from 1979 to 2018 were constructed using the GRU-GSWAT+ model first. The differences in streamflow characteristics, the shift of hydrological extreme pattern, and potential changes of the controlling factors before and after the abrupt changes were investigated. The results indicated that the abrupt change point (ACP) in streamflow occurred in 2000 in the Qarqan River Basin, 2002 in the Weigan River Basin, and 1994 in the Aksu River Basin and the Yarkant River Basin. A general decrease in streamflow before the ACP has shifted to a notable upward trend in the Qarqan River Basin and the Aksu River Basin, while minor upward fluctuations were observed in other basins. Moreover, the hydrological characteristics in extreme events vary dramatically before and after the ACPs, characterized by a pronouncing shift from drought-dominant pattern to wet events dominated pattern. The driven climate factors have been altered after the ACPs with notable spatial heterogeneity, in which temperature remained as the dominant role in meltwater-dominated basins while the influence of precipitation has increased after the ACPs, whereas the sensitivity of temperature on streamflow change has been enhanced in basins dominated by precipitation such as the Qarqan River Basin. Owing to the evident warming–wetting trend and glacier compensation effect, both the inter-annual and intra-annual streamflow fluctuations can be efficiently smoothed in basins with a high glacier area ratio (GAR). These findings provide a further understanding of the abrupt change in streamflow under the exacerbated climate and glacier change in mountainous arid regions.

The cinnamates having an ortho-formyl group can potentially form vinylogous iminium ion species under the catalysis of chiral amines, which facilitates the Diels–Alder cycloaddition reaction with the concurrently generated trienamines between dienals and amine catalysts in a regioselectivity umpolung manner. A cascade intramolecular aldol reaction was followed, finally furnishing polyhydrophenanthrene frameworks with excellent diastereo- and enantioselectivity.

This study selected Dendrobium officinaleprotocorms as the experimental material and used different light-quality treatments and calcium signalling inhibitors to explore the mechanism of the biological response of calcium to light quality. The results indicate that a 1:3 red:blue (R:B) light ratio promotes the accumulation of biomass and polysaccharides in the protocorm. Nevertheless, this effect can be entirely counteracted by calmodulin (CaM) inhibitors and calcium ion-chelating agents. The possible mechanisms of this effect are as follows: (1) The Ca2+-CaM signal-regulated photosynthetic apparatus is improved by the R:B 1:3 light, increasing the CaM content and Ca2+-ATPase activity. Thus, R:B 1:3 light increases the development of the photosynthetic apparatus in the D. officinaleprotocorm, enhances its photosynthetic productivity, and promotes the activities of sucrose phosphatase; accordingly, biomass and sucrose accumulation increase. (2) R:B 1:3 light enhances Ca2+-CaM signalling and regulates glycometabolic processes to promote the activities of sucrose synthase, thus increasing fructose and glucose levels and providing sufficient synthetic precursors to promote polysaccharide production.

Quinolones are widely used in the pharmaceutical industry; however, the high residue of these antibiotics has caused serious water quality issues, and their effective removal is still a great challenge. In this work, bimetallic magnetic FexMnycatalysts are prepared by a facile impregnation method and are efficient for photocatalytic removal of five typical quinolone pollutants without oxidant under simulated light irradiation. The fabricated bimetallic magnetic FexMnycatalyst with the Fe3+/Mn2+ratio of 1 : 1 exhibits a large surface area of 122.5 m2g−1, highly porous structure, rich defects and a covalent metal environment. These fabricated semiconductor catalysts can degrade 98.3% of ciprofloxacin (CIP), 96.0% of ofloxacin (OFL), 91.0% of enrofloxacin (ENR), 92.2% of levofloxacin (LEV), and 93.5% of norfloxacin (NOR) in 30 min without using any oxidant. The magnetic FexMnycatalysts can be simply recycled using a magnet and maintain high stability, avoiding complex recycling procedures. Even after five cycles, the degradation rate of CIP was still over 92.0%. The degradation performance is far superior to that of most previously reported candidates. The bimetallic FexMnycatalyst improves the ability to capture sunlight, increases the interface charge transfer rate, and inhibits the recombination of photogenerated electron–hole pairs. In addition, the mechanism and the main intermediates in the photocatalytic degradation of CIP are explored by quenching experiments, electron paramagnetic resonance (EPR) and liquid chromatography-mass spectrometry (LC-MS) analysis. These noble-metal free magnetic FexMnycatalysts provide a promising opportunity for advanced photocatalytic oxidation technology to treat wastewater.

The benzylic C–H group of α,α-dicyanoolefins from 3-substituted 1-indanones could be significantly activated via transmission along the aromatic system, thus enabling dynamic kinetic resolution via a traditional reversible deprotonation–protonation process. Enantioenriched 9-substituted 9H-fluorene frameworks were finally constructed through an asymmetric vinylogous Michael addition to nitroolefins, followed by a cascade cyclization and oxidative aromatization process, under the catalysis of a chiral bifunctional thiourea-tertiary amine.

In this study, we analyzed the effects of histology subtypes, lymph node N-stages, and the presence of extrathyroidal extensions on cancer-specific survival (CSS) and overall survival (OS) in patients with differentiated thyroid cancer.

A high-temperature all-fiber non-destructive multi-parameter sensing system is developed. The system can operate consistently in a wide range of temperature changes by specially designed active signal generation and detection units. It is capable of monitoring temperature up to 600°C and cracks on metal pipes with an acoustic wave generation unit and an acoustic detection unit. A gold-coated multi-mode fiber is used to deliver a laser pulse for acoustic excitation while minimizing parasitic acoustic signals at high temperature. An in-fiber Fabry–Perot fiber Bragg grating (FP-FBG) is fabricated in another single-mode fiber and bonded to the test object for acoustic detection. The FP-FBG avoids strain redistribution inside the bonder at high temperature to ensure consistent operation. The feasibility of the system for temperature monitoring and crack detection in real-world applications is also demonstrated on an industry-standard P91 pipe.

To prepare the highly active hydrodesulfurization (HDS) catalyst, modified Zr-KIT-5 materials were synthesized by in situ synthesis method and supported NiMoW trimetallic active phases for dibenzothiophene (DBT) and 4,6-dimethyldibenzothiphene (4,6-DMDBT) hydrodesulfurization reactions. The analysis of Fourier-transform infrared and X-ray photoelectron spectroscopy proved that Zr species had been incorporated into the skeleton of mesoporous KIT-5 material. Moreover, it was demonstrated from the Py-IR and high-resolution transmission electron microscopy characterizations that the embedded Zr species not only enhanced the acidity of catalysts but also modulated the distribution of active metals. Among all of the modified trimetallic catalysts, the NiMoW/ZrKT-60 displayed the highest HDS activities of DBT (99.5%) and 4,6-DMDBT (91.0%), which was derived from the open and large three-dimensional mesoporous channel, suitable acidity, and appropriate Mo(W)S2dispersion. Furthermore, for 4,6-DMDBT reaction, the NiMoW/ZrKT-60 catalyst with the highest B/L ratio (0.22) showed higher hydrogenation and the highest isomerization selectivity.

The utilization of abundant and renewable biomass to fabricate advanced functional materials is considered a promising route for environmental applications. Herein, Lignin-based porous carbon with layered graphene-like structure (LPC) is successfully synthesized and applied to efficiently remove Pb(II) and Cd(II). The as-synthesized LPC materials are systematically characterized and these results show that LPC has a porous graphene-like structure, facilitating the diffusion and immobilization of heavy metal ions. The influence of different reaction parameters (solution pH, initial concentration of metal ions, contact time and adsorbent amount) on the adsorption performance is investigated in details. The results demonstrate that LPC can achieve superior adsorption capacities of 250.5 mg g−1for Pb(II) and 126.4 mg g−1for Cd(II), which are far superior to the previously reported adsorbents. Pseudo-second order kinetics model and Freundlich isotherm model describe the adsorption process well. Furthermore, the exhausted LPC can be regenerated easily and exhibits the removal efficiency of 96% and 92% for Pb(II) and Cd(II) after five continuous runs, respectively. This study shows a sustainable strategy for the design of porous carbon material from naïve biomass and highlights the great potential in wastewater treatment.

Beta/FDU-12 (BF) series composite materials were successfully synthesized with different inorganic salts (KCl, MgCl2, MnCl2, and CuCl2). The supports and corresponding catalysts were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), pyridine-Fourier transform infrared spectroscopy (Py-FTIR), H2temperature-programmed reduction (H2-TPR), Raman, X-ray photoelectron spectra (XPS), and high-resolution transmission electron microscopy (HRTEM). NiMo/BF catalysts were evaluated for dibenzothiophene (DBT) hydrodesulfurization (HDS). Consequently, NiMo/BF–Mg catalyst displayed the highest HDS performance (98.58%), as the weight hourly space velocity (WHSV) was 10 h–1. The synergistic attribution of its prominent support texture, the excellent acid and redox properties of NiMo catalyst, including more B and L acids (193.6 and 118.0 μmol·g–1at 200 and 350 °C, respectively), strong metal–support interaction, smaller stacking number (3.75), shorter stacking length (3.11), higher dispersion degree (0.29), and higher sulfidation degree of Mo sulfide species (61.3%), result in high DBT HDS activity. Moreover, NiMo/BF–Mg catalyst exhibited a higher HYD/DDS ratio (0.29), due to the greater number of L acids and higher value of 0.23.

A series of Ti-KIT-5 materials with different ratios of Si/Ti were synthesized and employed as the supports to prepare the NiMo catalysts. All the modified supports and catalysts were measured by means of small-angle and wide-angle XRD, N2isotherm absorption–desorption, FTIR, XPS, Py-IR, and HRTEM techniques. The small-angle XRD and N2analysis characterization proved that the modified Ti-KT-xmaterials maintained the orderly mesoporous structure and displayed the larger pore size than the pure support. Additionally, results from the FTIR and XPS spectra demonstrated that Ti species were successfully embedded into the framework of KIT-5 material. It was noted that the introduction of suitable Ti species increased the amount of acid sites and promoted well distribution of the active metals. The hydrodenitrogenation performances of the NiMo/Ti-KT-xcatalysts were evaluated under the reaction conditions of a H2pressure of 4 MPa, a WHSV of 10 h–1, and different temperatures ranging from 340 to 400 °C. The modified NiMo/Ti-KIT-5 catalysts showed the higher catalytic activities than NiMo/KIT-5 catalyst, which was attributed to the larger pore size, more acid sites, and sulfide active metal species. Moreover, the NiMo/Ti-KT-20 catalyst showed the highest hydrodenitrogenation efficiencies (81.56%).

Highly ordered mesoporous silica with Pm3ncubic mesostructure and cube-like morphology was facilely fabricated in a cost-efficient aqueous-phase synthesis system. The obtained cubic mesoporous silica (CMS) modified with various aluminum contents were taken as supports to prepare NiMo/Al-CMS catalysts, and the corresponding hydrodesulfurization performance of dibenzothiophene was subsequently assessed. The results showed that as-prepared CMS exhibited a large surface area (865 m2/g) and pore volume (0.92 cm3/g). The incorporated aluminum brought many advantages such as enhanced acidity, modulated metal–support interaction, and improved active metals dispersity, all of which contributed to the high sulfidation degree of catalysts. As a result, the NiMo/Al-CMS-10 catalyst presented superior HDS activity and a higher selectivity for the direct desulfurization route, deriving from a synergistic effect of its admirable textural characteristics, increased acidic property, highly sulfided active phases, and well-dispersed MoS2slabs with moderate stacking layer and slab length.

Controversies regarding factors associated with distant metastasis in pediatric thyroid cancer remain among the scientific community. The aim of this study was to investigate factors influencing distant metastasis in pediatric thyroid cancer.We reviewed 1376 patients (aged 2 to 18 years) with thyroid cancer treated between 2003 and 2014. Data collected and analyzed included sex, race, age at diagnosis, year of diagnosis, pathological type, number of tumor foci, tumor extension, T-stage, N-stage, surgical procedure and radiation. Univariate and multivariate analyses were conducted to evaluate factors influencing distant metastasis of pediatric thyroid cancer.In the univariate analysis, factors influencing distant metastasis of thyroid cancer were age at diagnosis (P< 0.001), N-stage (P< 0.001), number of tumor foci (P= 0.003), tumor extension (P< 0.001) and T-stage (T1 vs T2 (P= 0.803), T3 (P< 0.001) and T4 (P< 0.001)). In multivariate analysis, factors influencing distant metastasis of thyroid cancer were age at diagnosis (P= 0.001), N-stage (P< 0.001) and T-stage (T1 vs T3 (P= 0.036) and T4 (P< 0.001)). Sex, race, year of diagnosis, pathological type, number of tumor foci, tumor extension, surgical procedure and radiation had no significant influence on distant metastasis (all P> 0.05). Furthermore, according to chi-squared test, younger pediatric thyroid cancer patients with higher T- and N-stages are more likely to have distant metastasis.Age at diagnosis, T-stage and N-stage influence distant metastasis of thyroid cancer patients aged 2 to 18 years; accordingly, more radical treatments may need to be used for patients with those risk elements.

This research reports on the catalytic performance of Co-BTC in solvent-free cycloaddition of CO2and styrene oxide for the production of cyclic carbonate using tetrabutylammonium bromide as a co-catalyst. The results demonstrated that the conversion of styrene oxide and the selectivity of the product were both more than 95% under relatively mild reaction conditions (10 bar CO2, 110 °C). In addition, the Co-BTC catalyst maintained its unique morphology and excellent catalytic performance even after recycling it for three times. Co-BTC reported as an efficient heterogeneous catalyst in this work. The acid–base property of Co-BTC catalyst was investigated by NH3and CO2temperature-programmed desorption methods, and it was found that the acidic and alkaline nature of the Co-BTC catalyst did not changed apparently after the catalyst was recycled. So it was confirmed that the Co-BTC catalytic cycloaddition reaction was closely related to the Lewis acid–base distribution.

Methane, one of the most abundant molecules on Earth and a major greenhouse gas, comes from renewable and fossil resources. The utilization of methane as a starting material for synthesis of chemicals is attractive but encounters numerous challenges due to high thermodynamic stability and extreme inertness of methane. Most of methane reactions occur at high temperatures and coincide with major emissions of CO2. Semiconductor photocatalysis offers an efficient alternative for methane conversion at room temperature.

Diabetes is a complex metabolic syndrome that is characterized by prolonged high blood glucose levels and frequently associated with life-threatening complications1,2. Epidemiological studies have suggested that diabetes is also linked to an increased risk of cancer3–5. High glucose levels may be a prevailing factor that contributes to the link between diabetes and cancer, but little is known about the molecular basis of this link and how the high glucose state may drive genetic and/or epigenetic alterations that result in a cancer phenotype. Here we show that hyperglycaemic conditions have an adverse effect on the DNA 5-hydroxymethylome. We identify the tumour suppressor TET2 as a substrate of the AMP-activated kinase (AMPK), which phosphorylates TET2 at serine 99, thereby stabilizing the tumour suppressor. Increased glucose levels impede AMPK-mediated phosphorylation at serine 99, which results in the destabilization of TET2 followed by dysregulation of both 5-hydroxymethylcytosine (5hmC) and the tumour suppressive function of TET2 in vitro and in vivo. Treatment with the anti-diabetic drug metformin protects AMPK-mediated phosphorylation of serine 99, thereby increasing TET2 stability and 5hmC levels. These findings define a novel ‘phospho-switch’ that regulates TET2 stability and a regulatory pathway that links glucose and AMPK to TET2 and 5hmC, which connects diabetes to cancer. Our data also unravel an epigenetic pathway by which metformin mediates tumour suppression. Thus, this study presents a new model for how a pernicious environment can directly reprogram the epigenome towards an oncogenic state, offering a potential strategy for cancer prevention and treatment. Modulation of DNA 5-hydroxymethylcytosine by glucose reveals an AMPK–TET2–5hmC axis that links diabetes to cancer.

Perhaps the most ambitious social policy carried out by the Incas, the mitmaqprogram resettled one third to one quarter of subject populations for the purposes of control and producing for the state. Ethnohistoric sources suggest that the relocated people, called mitmaqkuna, were given access to fertile lands and enjoyed elevated social status and freedoms bestowed to them by the Incas. Until now, these claims have not been tested with archaeological evidence. This paper evaluates the ethnohistoric claims through the geochemical analysis of 84 obsidian artifacts from a probable mitmaqkunaagricultural labor colony called Yanawilka, located in Vilcashuamán province, Peru. There is evidence that access to obsidian was restricted for the inhabitants of Yanawilka. The obsidian was mostly from the Quispisissa source, but the relative scarcity, small flake size, and evidence for conservation of raw material suggests that access to this high-quality source was limited and not due to direct procurement.