PARP1 UFMylation ensures the stability of stalled replication forks.

The S-phase checkpoint involving CHK1 is essential for fork stability in response to fork stalling. PARP1 acts as a sensor of replication stress and is required for CHK1 activation. However, it is unclear how the activity of PARP1 is regulated. Here, we found that UFMylation is required for the efficient activation of CHK1 by UFMylating PARP1 at K548 during replication stress. Inactivation of UFL1, the E3 enzyme essential for UFMylation, delayed CHK1 activation and inhibits nascent DNA degradation during replication blockage as seen in PARP1-deficient cells. An in vitro study indicated that PARP1 is UFMylated at K548, which enhances its catalytic activity. Correspondingly, a PARP1 UFMylation-deficient mutant (K548R) and pathogenic mutant (F553L) compromised CHK1 activation, the restart of stalled replication forks following replication blockage, and chromosome stability. Defective PARP1 UFMylation also resulted in excessive nascent DNA degradation at stalled replication forks. Finally, we observed that PARP1 UFMylation-deficient knock-in mice exhibited increased sensitivity to replication stress caused by anticancer treatments. Thus, we demonstrate that PARP1 UFMylation promotes CHK1 activation and replication fork stability during replication stress, thus safeguarding genome integrity.

Quasi-open Cu(I) sites for efficient CO separation with high O2/H2O tolerance.

Carbon monoxide (CO) separation relies on chemical adsorption but suffers from the difficulty of desorption and instability of open metal sites against O2, H2O and so on. Here we demonstrate quasi-open metal sites with hidden or shielded coordination sites as a promising solution. Possessing the trigonal coordination geometry (sp2), Cu(I) ions in porous frameworks show weak physical adsorption for non-target guests. Rational regulation of framework flexibility enables geometry transformation to tetrahedral geometry (sp3), generating a fourth coordination site for the chemical adsorption of CO. Quantitative breakthrough experiments at ambient conditions show CO uptakes up to 4.1 mmol g-1 and CO selectivity up to 347 against CO2, CH4, O2, N2 and H2. The adsorbents can be completely regenerated at 333-373 K to recover CO with a purity of >99.99%, and the separation performances are stable in high-concentration O2 and H2O. Although CO leakage concentration generally follows the structural transition pressure, large amounts (>3 mmol g-1) of ultrahigh-purity (99.9999999%, 9N; CO concentration < 1 part per billion) gases can be produced in a single adsorption process, demonstrating the usefulness of this approach for separation applications.

Metal-Organic Framework Based Sensors for Benzene Vapor.

Sensing of benzene vapor is a hot spot due to the volatile drastic carcinogen even at trace concentration. However, achieving convenient and rapid detection is still a challenge. As a sort of functional porous material, metal-organic frameworks (MOFs) have been developed as detection sensors by adsorbing benzene vapor and converting it into other signals (fluorescence intensity/wavelength, chemiresistive, weight or color, etc.). Supramolecular interaction between benzene molecules and the host framework, aperture size/shape and structural flexibility are influential factors in the performance of MOF-based sensors. Therefore, enhancing the host-guest interactions between the host framework and benzene molecules, or regulating the diffusion rate of benzene molecules by changing the aperture size/shape and flexibility of the host framework to enhance the detection signal are effective strategies for constructing MOF-based sensors. This concept highlights several types of MOF-based sensors for the detection of benzene vapor.

Free-Space and Fiber-Integrated Measurement-Device-Independent Quantum Key Distribution under High Background Noise.

Measurement-device-independent quantum key distribution (MDI QKD) provides immunity against all attacks targeting measurement devices. It is essential to implement MDI QKD in the future global-scale quantum communication network. Toward this goal, we demonstrate a robust MDI QKD fully covering daytime, overcoming the high background noise that prevents BB84 protocol even when using a perfect single-photon source. Based on this, we establish a hybrid quantum communication network that integrates free-space and fiber channels through Hong-Ou-Mandle (HOM) interference. Additionally, we investigate the feasibility of implementing HOM interference with moving satellites. Our results serve as a significant cornerstone for future integrated space-ground quantum communication networks that incorporate measurement-device-independent security.

Fluorescence Enhancement of a Metal-Organic Framework for Ultra-Efficient Detection of Trace Benzene Vapor.

Indoor detection of volatile organic compounds (VOCs) concentration is necessary due to the serious toxicity hazards even at trace level. However, physisorbents usually exhibit weak interactions especially in the presence of trace concentrations of VOCs, thus exhibiting poor responsive signal. Herein, we report a new flexible metal-organic framework (MOF) that exhibits interesting pore-opening behavior after immersing in H2 O. The pore-opening phase shows significant (≈116 folds) and extremely fast (<1 minute) fluorescence enhancement after being exposed to saturated benzene vapor. The limit of detection concentration for benzene vapor can be calculated as 0.133 mg L-1 . Thus this material represents the first MOF to achieve visual detection of trace benzene vapor by the naked eyes. Theoretical calculations and single-crystal structure reveal that the special "bilateral π-π stacking" interactions between the host and guest, which facilitate electron transfer and greatly enhance the intensity of fluorescence.

BAIAP2L2 is required for the maintenance of mechanotransducing stereocilia of cochlear hair cells.

Stereocilia are actin-based cell protrusions of inner ear hair cells that play an essential role in mechano-electrical transduction (MET). Stereocilia are organized into several rows of increasing heights with the MET protein complex localized at the tips of shorter row stereocilia. At the tips of shorter row mechanotransducing stereocilia also resides a so-called "row 2 protein complex" whose dysfunction causes degeneration of the mechanotransducing stereocilia. In the present work, we show that BAIAP2L2 is localized at the tips of shorter row stereocilia in neonatal and adult mouse cochlear hair cells. Baiap2l2 inactivation causes degeneration of the mechanotransducing stereocilia, which eventually leads to profound hearing loss in mice of either sex. Consistently, electrophysiology and FM 1-43FX dye uptake results confirm that MET currents are compromised in Baiap2l2 knockout mice. Moreover, BAIAP2L2 binds to known row 2 complex components EPS8L2, TWF2, and CAPZB2, and the stereociliary tip localization of CAPZB2 is dependent on functional BAIAP2L2. Interestingly, BAIAP2L2 also binds to CIB2, a known MET complex component, and the stereociliary tip localization of BAIAP2L2 is abolished in Cib2 knockout mice. In conclusion, our present data suggest that BAIAP2L2 is a row 2 complex component, and is required for the maintenance of mechanotransducing stereocilia. Meanwhile, specific MET components such as CIB2 might play a direct role in stereocilia maintenance through binding to BAIAP2L2.

New-onset autoimmune phenomena post-COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented setback for global economy and health. Vaccination is one of the most effective interventions to substantially reduce severe disease and death due to SARS-CoV-2 infection. Vaccination programmes are being rolled out globally, but most of these vaccines have been approved without extensive studies on their side-effects and efficacy. Recently, new-onset autoimmune phenomena after COVID-19 vaccination have been reported increasingly (e.g. immune thrombotic thrombocytopenia, autoimmune liver diseases, Guillain-Barré syndrome, IgA nephropathy, rheumatoid arthritis and systemic lupus erythematosus). Molecular mimicry, the production of particular autoantibodies and the role of certain vaccine adjuvants seem to be substantial contributors to autoimmune phenomena. However, whether the association between COVID-19 vaccine and autoimmune manifestations is coincidental or causal remains to be elucidated. Here, we summarize the emerging evidence about autoimmune manifestations occurring in response to certain COVID-19 vaccines. Although information pertaining to the risk of autoimmune disease as a consequence of vaccination is controversial, we merely propose our current understanding of autoimmune manifestations associated with COVID-19 vaccine. In fact, we do not aim to disavow the overwhelming benefits of mass COVID-19 vaccination in preventing COVID-19 morbidity and mortality. These reports could help guide clinical assessment and management of autoimmune manifestations after COVID-19 vaccination.

COVID-19 and inflammatory bowel disease crosstalk: From emerging association to clinical proposal.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause coronavirus disease 2019 (COVID-19), an acute respiratory inflammation that has emerged worldwide since December 2019, and it quickly became a global epidemic. Inflammatory bowel disease (IBD) is a group of chronic nonspecific intestinal inflammatory diseases whose etiology has not been elucidated. The two have many overlapping symptoms in clinical presentation, such as abdominal pain, diarrhea, pneumonia, etc. Imbalance of the autoimmune system in IBD patients and long-term use of immunosuppressive drugs may increase the risk of infection; and systemic symptoms caused by COVID-19 may also induce or exacerbate intestinal inflammation. It has been found that the SARS-CoV-2 receptor angiotensin converting enzyme 2, which is highly expressed in the lung and intestine, is an inflammatory protective factor, and is downregulated and upregulated in COVID-19 and IBD, respectively, suggesting that there may be a coregulatory pathway. In addition, the immune activation pattern of COVID-19 and the cytokine storm in the inflammatory response have similar roles in IBD, indicating that the two diseases may influence each other. Therefore, this review aimed to address the following research questions: whether SARS-CoV-2 infection leads to the progression of IBD; whether IBD increases the risk of COVID-19 infection and poor prognosis; possible common mechanisms and genetic cross-linking between the two diseases; new treatment and care strategies for IBD patients, and the feasibility and risk of vaccination in the context of the COVID-19 epidemic.

Experimental Side-Channel-Secure Quantum Key Distribution.

Quantum key distribution can provide unconditionally secure key exchange for remote users in theory. In practice, however, in most quantum key distribution systems, quantum hackers might steal the secure keys by observing the side channels in the emitted photons, such as the photon frequency spectrum, emission time, propagation direction, spatial angular momentum, and so on. It is hard to prevent such kinds of attacks because side channels may exist in many dimensions of the emitted photons. Here we report an experimental realization of a side-channel-secure quantum key distribution protocol which is not only measurement-device independent, but also immune to all side-channel attacks to the photons emitted from Alice's and Bob's labs. We achieve a secure key rate of 1.73×10^{-6} per pulse through 50 km fiber spools.

The E3 ubiquitin ligase APC/CCdh1 degrades MCPH1 after MCPH1-ßTrCP2-Cdc25A-mediated mitotic entry to ensure neurogenesis.

Mutations of microcephalin (MCPH1) can cause the neurodevelopmental disorder primary microcephaly type 1. We previously showed that MCPH1 deletion in neural stem cells results in early mitotic entry that distracts cell division mode, leading to exhaustion of the progenitor pool. Here, we show that MCPH1 interacts with and promotes the E3 ligase ßTrCP2 to degrade Cdc25A independent of DNA damage. Overexpression of ßTrCP2 or the knockdown of Cdc25A remedies the high mitotic index and rescues the premature differentiation of Mcph1-deficient neuroprogenitors in vivo MCPH1 itself is degraded by APC/CCdh1, but not APC/CCdc20, in late mitosis and G1 phase. Forced MCPH1 expression causes cell death, underlining the importance of MCPH1 turnover after mitosis. Ectopic expression of Cdh1 leads to premature differentiation of neuroprogenitors, mimicking differentiation defects of Mcph1-knockout neuroprogenitors. The homeostasis of MCPH1 in association with the ubiquitin-proteasome system ensures mitotic entry independent of cell cycle checkpoint. This study provides a mechanistic understanding of how MCPH1 controls neural stem cell fate and brain development.

Field Test of Twin-Field Quantum Key Distribution through Sending-or-Not-Sending over 428 km.

Quantum key distribution endows people with information-theoretical security in communications. Twin-field quantum key distribution (TF-QKD) has attracted considerable attention because of its outstanding key rates over long distances. Recently, several demonstrations of TF-QKD have been realized. Nevertheless, those experiments are implemented in the laboratory, and therefore a critical question remains about whether the TF-QKD is feasible in real-world circumstances. Here, by adopting the sending-or-not-sending twin-field QKD (SNS-TF-QKD) with the method of actively odd parity pairing (AOPP), we demonstrate a field-test QKD over 428 km of deployed commercial fiber and two users are physically separated by about 300 km in a straight line. To this end, we explicitly measure the relevant properties of the deployed fiber and develop a carefully designed system with high stability. The secure key rate we achieved breaks the absolute key rate limit of repeaterless QKD. The result provides a new distance record for the field test of both TF-QKD and all types of fiber-based QKD systems. Our work bridges the gap of QKD between laboratory demonstrations and practical applications and paves the way for an intercity QKD network with measurement-device-independent security.

Association of MALAT-1 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus.

Background: Abnormal expression and function of long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene single-nucleotide polymorphisms (SNPs) with susceptibility and clinical characteristics of SLE patients. Methods: A case-control study including 489 SLE patients and 492 healthy controls was conducted. Four MALAT-1 SNPs (rs4102217, rs591291, rs11227209, and rs619586) were genotyped in all subjects, their correlation with SLE susceptibility and clinical characteristics were also analyzed. Results: Results showed that the rs4102217 locus was associated with the risk of SLE. In recessive models, the GG+CG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.036, OR = 0.348, 95% CI: 0.124-0.975). In additive models, the GG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.040, OR = 0.355, 95% CI: 0.127-0.996). However, no association was found between MALAT-1 gene polymorphism and clinical manifestations of SLE (all p > 0.05). Conclusion: In summary, MALAT-1 rs4102217 is associated with susceptibility to SLE, suggesting that MALAT-1 may play a role in SLE.

Emerging role of ficolins in autoimmune diseases.

Ficolins are pattern-recognition molecules (PRMs) that could form complexes with mannose-binding lectin-associated serine proteases (MASPs) to trigger complement activation via the lectin pathway, thereby mediating a series of immune responses including opsonization, phagocytosis and cytokine production. In the past few decades, accumulating evidence have suggested that ficolins play a major role in the onset and development of several autoimmune diseases (ADs), including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), Type 1 diabetes (T1D), inflammatory bowel disease (IBD), etc. In this review, we synthesized previous literatures and recent advances to elucidate the immunological regulations of ficolins and discuss the potential diagnostic ability of ficolins in ADs, as well as giving an insight into the future therapeutic options for ficolins in ADs.

Intermediate-sized molecular sieving of styrene from larger and smaller analogues.

Molecular sieving can lead to ultrahigh selectivity and low regeneration energy because it completely excludes all larger molecules via a size restriction mechanism. However, it allows adsorption of all molecules smaller than the pore aperture and so separations of complicated mixtures can be hindered. Here, we report an intermediate-sized molecular sieving (iSMS) effect in a metal-organic framework (MAF-41) designed with restricted flexibility, which also exhibits superhydrophobicity and ultrahigh thermal/chemical stabilities. Single-component isotherms and computational simulations show adsorption of styrene but complete exclusion of the larger analogue ethylbenzene (because it exceeds the maximal aperture size) and smaller toluene/benzene molecules that have insufficient adsorption energy to open the cavity. Mixture adsorption experiments show a high styrene selectivity of 1,250 for an ethylbenzene/styrene mixture and 3,300 for an ethylbenzene/styrene/toluene/benzene mixture (orders of magnitude higher than previous reports). This produces styrene with a purity of 99.9%+ in a single adsorption-desorption cycle. Controlling/restricting flexibility is the key for iSMS and can be a promising strategy for discovering other exceptional properties.

Discovery of new serum biomarker panels for systemic lupus erythematosus diagnosis.

OBJECTIVE: Clinical diagnosis of SLE is currently challenging due to its heterogeneity. Many autoantibodies are associated with SLE and are considered potential diagnostic markers, but systematic screening and validation of such autoantibodies is lacking. This study aimed to systematically discover new autoantibodies that may be good biomarkers for use in SLE diagnosis. METHODS: Sera from 15 SLE patients and 5 healthy volunteers were analysed using human proteome microarrays to identify candidate SLE-related autoantibodies. The results were validated by screening of sera from 107 SLE patients, 94 healthy volunteers and 60 disease controls using focussed arrays comprised of autoantigens corresponding to the identified candidate antibodies. Logistic regression was used to derive and validate autoantibody panels that can discriminate SLE disease. Extensive ELISA screening of sera from 294 SLE patients and 461 controls was performed to validate one of the newly discovered autoantibodies. RESULTS: A total of 31, 11 and 18 autoantibodies were identified to be expressed at significantly higher levels in the SLE group than in the healthy volunteers, disease controls and healthy volunteers plus disease control groups, respectively, with 25, 7 and 13 of these differentially expressed autoantibodies being previously unreported. Diagnostic panels comprising anti-RPLP2, anti-SNRPC and anti-PARP1, and anti-RPLP2, anti-PARP1, anti-MAK16 and anti- RPL7A were selected. Performance of the newly discovered anti-MAK16 autoantibody was confirmed by ELISA. Some associations were seen with clinical characteristics of SLE patients, such as disease activity with the level of anti-PARP1 and rash with the level of anti-RPLP2, anti-MAK16 and anti- RPL7A. CONCLUSION: The combined autoantibody panels identified here show promise for the diagnosis of SLE and for differential diagnosis of other major rheumatic immune diseases.

Sending-or-Not-Sending with Independent Lasers: Secure Twin-Field Quantum Key Distribution over 509 km.

Twin-field (TF) quantum key distribution (QKD) promises high key rates over long distances to beat the rate-distance limit. Here, applying the sending-or-not-sending TF QKD protocol, we experimentally demonstrate a secure key distribution that breaks the absolute key-rate limit of repeaterless QKD over a 509-km-long ultralow loss optical fiber. Two independent lasers are used as sources with remote-frequency-locking technique over the 500-km fiber distance. Practical optical fibers are used as the optical path with appropriate noise filtering; and finite-key effects are considered in the key-rate analysis. The secure key rate obtained at 509 km is more than seven times higher than the relative bound of repeaterless QKD for the same detection loss. The achieved secure key rate is also higher than that of a traditional QKD protocol running with a perfect repeaterless QKD device, even for an infinite number of sent pulses. Our result shows that the protocol and technologies applied in this experiment enable TF QKD to achieve a high secure key rate over a long distribution distance, and is therefore practically useful for field implementation of intercity QKD.

Template Thermolysis to Create a Carbon Dots-Embedded Mesoporous Titanium-Oxo Sulfate Framework for Visible-Light Photocatalytic Applications.

An organo-templated titanium-oxo sulfate of the formulation (H2nep)[TiO(SO4)2] (denoted as TiOS, nep = N-ethylpiperazine) was synthesized under solvent-free conditions. The framework of TiOS is assembled from the [TiO(SO4)2]n2n- infinite chains interconnected by the H2nep cations through H-bond networks. After thermal treatment under vacuum conditions, the organic template H2nep was partially decomposed and converted into N-doped carbon dots (N-CDs), resulting in the N-CDs@TiOS composite material with retained crystallinity of the parent TiOS. The thermolysis of organic templates generates meso-cavities in the framework, rendering N-CDs@TiOS with a mesoporous structure. Photoelectrochemical and photocatalytic experiments show that the presence of N-CDs substantially improved visible-light-driven photocatalytic activity of N-CDs@TiOS compared to that of TiOS. The template thermolysis strategy gives an effective approach to construct the CDs-sensitized Ti-based mesoporous open-framework materials for visible-light photocatalytic applications.

Kinetic Analysis for Reaction of Cyclopentadiene with Hydroperoxyl Radical under Low- and Medium-Temperature Combustion.

The kinetic data of cyclopentadiene C5H6 oxidation reactions are significant for the construction of aromatics oxidation mechanism because cyclopentadiene C5H6 has been proved to be an important intermediate in the aromatics combustion. Kinetics for the elementary reactions on the potential energy surface (PES) relevant for the C5H6 + HO2 reaction are studied in this work. Stationary points on the PES are calculated by employing the CCSD(T)/cc-pVTZ//B3LYP/6-311G(d,p) level of theory. High-pressure limit and pressure-dependent rate constants for elementary reactions on this PES are calculated using conventional transition state theory (TST), variational transition-state theory (VTST) and Rice-Ramsberger-Kassel-Marcus/master equation (RRKM/ME) theory. In this work, the reaction channels for the C5H6 + HO2 reaction, which include H-abstraction channels from C5H6 by HO2 to form the C5H5 + H2O2 and the addition channels through well-skipping pathways to form the bimolecular products C5H7 + O2 or C5H6O + OH, or through C5H7O2 stabilization and its unimolecular decomposition to form the bimolecular products C5H7 + O2 or C5H6O + OH, namely sequential pathways, are studied. Also, the consuming reaction channels for the compounds C5H6O and C5H7 in the addition products are studied. The dominant reaction channels for these reactions are unraveled through comparing the energy barriers and rate constants of all elementary reactions and it is found: (1) HO2 addition to cyclopentadiene C5H6 is more important than direct H-abstraction. (2) in the HO2 addition channels, the well-skipping pathways and sequential pathways are competing and the well-skipping pathways will be favor in the higher pressures and the sequential pathways will be favor in the higher temperature. (3) The major consumption reaction channel for the five-member-ring compound C5H6O is the reaction channel to form C4H6 + CO and the major consumption reaction channel for the five-member-ring compound C5H7 is the reaction channel to form C3H5 + C2H2. High-pressure limit rate constants and pressure-dependent rate constants for elementary reactions on the PES are calculated, which will be useful in modeling the oxidation of aromatic compounds at low- and medium-temperatures.

D-penicillamine modified copper nanoparticles for fluorometric determination of histamine based on aggregation-induced emission.

A fluorometric method for the determination of histamine has been developed based on aggregation-induced emission (AIE) effect of D-penicillamine capped copper nanoparticles (DPA-CuNPs). The fluorescent DPA-CuNPs were synthesized by a one-pot method using D-penicillamine as both reducing agent and stabilizing ligand. The size, morphology and physical chemical properties of DPA-CuNPs were examined by transmission electron microscopy (TEM), fluorescence spectroscopy, fourier transform infrared spectroscopy (FTIR) and absorption spectroscopy. The DPA-CuNPs exhibit AIE effect and show intense red fluorescence (650 nm). In the presence of histamine, DPA-CuNPs are dispersed into small homogeneous particles, causing fluorescence quenching. Based on this reaction, a histamine sensor is constructed. The fluorescence of the CuNPs solution has a good linear relationship with histamine concentration in the range 0.05 µM to 5 µM and the determination limit (3σ/slope) is 30 nM. The estimated method was successfully applied to the determination of histamine in fish, pork and red wine. Graphical abstract Schematic representation of copper nanoparticles for histamine analysis. In the presence of histamine, the strong red fluorescence of copper nanoparticles is obvious decreased through interaction of copper nanoparticles and histamine.

Experimental Twin-Field Quantum Key Distribution through Sending or Not Sending.

Channel loss seems to be the most severe limitation on the practical application of long distance quantum key distribution. The idea of twin-field quantum key distribution can improve the key rate from the linear scale of channel loss in the traditional decoy-state method to the square root scale of the channel transmittance. However, the technical demands are rather tough because they require single photon level interference of two remote independent lasers. Here, we adopt the technology developed in the frequency and time transfer to lock two independent laser wavelengths and utilize additional phase reference light to estimate and compensate the fiber fluctuation. Further, with a single photon detector with a high detection rate, we demonstrate twin field quantum key distribution through the sending-or-not-sending protocol with a realistic phase drift over 300 km optical fiber spools. We calculate the secure key rates with the finite size effect. The secure key rate at 300 km (1.96×10^{-6}) is higher than that of the repeaterless secret key capacity (8.64×10^{-7}).