Comparative efficacy and safety of JAK/TYK2 inhibitors and other oral drugs for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis.

Background Janus kinase (JAK)/tyrosine kinase 2 (TYK2) inhibitors are novel treatments for moderate-to-severe plaque psoriasis. Objective To perform a network meta-analysis to compare the efficacy and safety of TYK2 inhibitors with other oral drugs in moderate-to-severe psoriasis. Methods Eligible randomised clinical trials (RCTs) were identified from public databases (published before November 2, 2023). Random-effect frequentist network meta-analysis was performed with ranking based on the surface under the cumulative ranking curve (SUCRA) of Physician's Global Assessment of "clear" or "almost clear" (PGA 0/1), 75% reduction from baseline in Psoriasis Area and Severity Index (PASI-75). Results Twenty RCTs containing 7,564 patients with moderate-to-severe psoriasis were included. Deucravacitinib at all dose levels (except for 3 mg every other day) and tofacitinib (10 mg BID) ranked best in achieving PGA 0/1 and PASI-75 at 12- 16 weeks. Tofacitinib (10 mg BID) was considered the most unsafe. Analysis of Ranking according to efficacy and safety showed deucravacitinib (3 mg QD and 3 mg BID) was the best treatment. Analysis of Ranking according to efficacy and safety showed deucravacitinib (3 mg QD and 3 mg BID) was the best treatment. Limitations Insufficiency of eligible data and no long-term follow-up data. Conclusion Deucravacitinib showed superior efficacy and safety for treating moderate-to-severe psoriasis over other included drugs.

A Retrospective Analysis of Risk Factors for Atopic Dermatitis Severity.

Background: Atopic dermatitis (AD) has the highest burden of any skin disease; however, the severity-associated factors remain unclear. Objective: To evaluate potential severity-associated factors of AD and to design and validate a severity prediction model to inform the management of AD patients. Methods: A cross-sectional study of 900 AD patients was conducted from December 2021 to October 2022 at our hospital. The primary outcome was disease severity, categorized as mild, moderate, or severe using the scoring atopic dermatitis index. Ordinal logistic regression and bootstrapped validation were used to derive and internally validate the model. Results: Increasing age, elevated eosinophil level, higher economic status, and urban residence were associated with severe AD. Breastfeeding, disinfectants and topical emollients use, and short duration of bathing were associated with mild AD. In the prediction model, predictors included age, eosinophil and economic status, residence, feeding, disinfectants and emollients use, and duration of bathing. Prediction models demonstrated good discrimination (bias-corrected concordance index [c-index] = 0.72) and good calibration. Conclusion: Risk factors for the severity of AD were identified that could aid the early prediction of AD progression. The predictive model included variables that are easily evaluated and could inform personalized prevention and therapy.

Successful treatment of classic Kaposi sarcoma with Trichophyton rubrum-infected onychomycosis and tinea pedis utilizing combination of oral itraconazole and thalidomide.

Kaposi sarcoma (KS) is a vascular proliferative tumor caused by human herpesvirus 8. At present, the treatment of KS is difficult and refractory. Here, we report a 68-year-old man who was diagnosed with a classical KS with tinea pedis and onychomycosis, infected by Trichophyton rubrum, and treated with itraconazole and thalidomide after locational excision of several bigger nodules. The lesions were relieved during treatment, and recurred after discontinuation. Retreatment still achieved good effect and the therapy was tapered down after control. After the whole course of treatment, the skin lesions subsided significantly without obvious adverse reactions, which showed that itraconazole combined with thalidomide may be another effective and safe treatment for KS in some cases.

Continuous variable quantum key distribution based on simultaneous quantum and classical communication in the terahertz band.

Continuous variable quantum key distribution (CVQKD) based on a simultaneous quantum and classical communication (SQCC) protocol can use a single coherent communication system for multiple purposes. In this paper, we propose an inter-satellite SQCC-CVQKD scheme in the terahertz (THz) band. This scheme performs classical modulation at the sending end, followed by quantum Gaussian modulation operations. At the receiving end, an amplifier is used to amplify and demultiplex the received signal, and, finally, a homodyne detector or heterodyne detector is selected for decoding. We have demonstrated the security of the SQCC-CVQKD system in the THz band, and a performance analysis of the scheme is given in the finite-size regime. The simulation results show that this scheme has a higher secret key rate and stronger anti-interference ability in practice. This work provides an effective way to construct wireless quantum communication networks.

Pyrimidine catabolism is required to prevent the accumulation of 5-methyluridine in RNA.

5-Methylated cytosine is a frequent modification in eukaryotic RNA and DNA influencing mRNA stability and gene expression. Here we show that free 5-methylcytidine (5mC) and 5-methyl-2'-deoxycytidine are generated from nucleic acid turnover in Arabidopsis thaliana, and elucidate how these cytidines are degraded, which is unclear in eukaryotes. First CYTIDINE DEAMINASE produces 5-methyluridine (5mU) and thymidine which are subsequently hydrolyzed by NUCLEOSIDE HYDROLASE 1 (NSH1) to thymine and ribose or deoxyribose. Interestingly, far more thymine is generated from RNA than from DNA turnover, and most 5mU is directly released from RNA without a 5mC intermediate, since 5-methylated uridine (m5U) is an abundant RNA modification (m5U/U ∼1%) in Arabidopsis. We show that m5U is introduced mainly by tRNA-SPECIFIC METHYLTRANSFERASE 2A and 2B. Genetic disruption of 5mU degradation in the NSH1 mutant causes m5U to occur in mRNA and results in reduced seedling growth, which is aggravated by external 5mU supplementation, also leading to more m5U in all RNA species. Given the similarities between pyrimidine catabolism in plants, mammals and other eukaryotes, we hypothesize that the removal of 5mU is an important function of pyrimidine degradation in many organisms, which in plants serves to protect RNA from stochastic m5U modification.

N4-acetylation of cytidine in mRNA plays essential roles in plants.

The biological function of RNA can be modulated by base modifications. Here, we unveiled the occurrence of N4-acetylation of cytidine in plant RNA, including mRNA, by employing LC-MS/MS and acRIP-seq. We identified 325 acetylated transcripts from the leaves of 4-week-old Arabidopsis (Arabidopsis thaliana) plants and determined that 2 partially redundant N-ACETYLTRANSFERASEs FOR CYTIDINE IN RNA (ACYR1 and ACYR2), which are homologous to mammalian NAT10, are required for acetylating RNA in vivo. A double-null mutant was embryo lethal, while eliminating 3 of the 4 ACYR alleles led to defects in leaf development. These phenotypes could be traced back to the reduced acetylation and concomitant destabilization of the transcript of TOUGH, which is required for miRNA processing. These findings indicate that N4-acetylation of cytidine is a modulator of RNA function with a critical role in plant development and likely many other processes.

A Distributed Architecture for Secure Delegated Quantum Computation.

In this paper, we propose a distributed secure delegated quantum computation protocol, by which an almost classical client can delegate a (dk)-qubit quantum circuit to d quantum servers, where each server is equipped with a 2k-qubit register that is used to process only k qubits of the delegated quantum circuit. None of servers can learn any information about the input and output of the computation. The only requirement for the client is that he or she has ability to prepare four possible qubits in the state of (|0⟩+eiθ|1⟩)/2, where θ∈{0,π/2,π,3π/2}. The only requirement for servers is that each pair of them share some entangled states (|0⟩|+⟩+|1⟩|-⟩)/2 as ancillary qubits. Instead of assuming that all servers are interconnected directly by quantum channels, we introduce a third party in our protocol that is designed to distribute the entangled states between those servers. This would simplify the quantum network because the servers do not need to share a quantum channel. In the end, we show that our protocol can guarantee unconditional security of the computation under the situation where all servers, including the third party, are honest-but-curious and allowed to cooperate with each other.

Composable security for inter-satellite continuous-variable quantum key distribution in the terahertz band.

Continuous-variable quantum key distribution (CVQKD) can be effectively compatible with off-the-shelf communication systems and has been proven to be the security against collective attacks in the finite-size regime and composability. In this paper, we classify three different trust levels for the loss and noise experienced by the sender and receiver. Based on these trust levels, we derive the composable finite-size security bounds of inter-satellite CVQKD in the terahertz (THz) band. We also show how these trust levels can nontrivially increase the composable secret key rates of THz-CVQKD and tolerate higher loss. Furthermore, the numerical simulations strongly support the feasibility of inter-satellite THz-CVQKD even in the worst trust level. This work provides an efficient path for building an inter-satellite quantum communication network.

Efficacy of PD-1 Inhibitor Combined with Bevacizumab in Treatment of Advanced Endometrial Cancer Patients with Mismatch Repair Deficiency (dMMR)/High-Level Microsatellite Instability (MSI-H).

BACKGROUND Mismatch repair deficiency (dMMR) is associated with endometrial cancers, yet it remains unknown how this information could be incorporated into adjuvant treatment paradigms. We performed this cohort study to identify the effect of dMMR status on the prognosis of patients with advanced endometrial cancer treated with PD-1 inhibitor and bevacizumab. MATERIAL AND METHODS We enrolled 93 patients with advanced endometrial cancer and divided them into an observation group (n=52) and a control group (n=41) according to the treatment. The control group was treated with bevacizumab combined with paclitaxel chemotherapy, while the observation group was treated with PD-1inhibitor combined with bevacizumab. The basic characteristics and overall survival times were compared between the 2 groups. RESULTS There was no significant difference in age, course of disease, clinical stage, or pathological type. The proportion of patients with dMMR and high-level microsatellite instability (MSI-H) were balanced in the 2 groups. Patients in the observation group had longer overall survival than those in the control group (33.2 months vs 21.8 months). Moreover, in the observation group, the median OS of dMMR patients was not detected, while the median OS of PMMR patients was 29.2 months (P<0.01). In the control group, the median OS of dMMR patients was 12.4 months, and that of PMMR patients was 24.1 months (P<0.01). CONCLUSIONS Advanced endometrial cancer patients with dMMR/MSI-H treated with PD-1 inhibitor plus bevacizumab had longer overall survival (OS) than those treated with bevacizumab plus paclitaxel chemotherapy.

FL-QKD based on optical-THz biphotons generated by spontaneous parametric downconversion in inter-satellite wireless communication.

Floodlight quantum key distribution (FL-QKD) is a new QKD protocol that can achieve a 2 Gbps secret key rate (SKR) in a 50 km fiber link without multiplexing technology [Q. Zhuang et al., Phys. Rev. A94, 012322 (2016)PLRAAN1050-294710.1103/PhysRevA.94.012322]. In this paper, we propose a wireless FL-QKD at terahertz bands (THz-FL-QKD) in inter-satellite links. THz-FL-QKD is the two-way protocol that sends quantum signals in the forward channel, modulates and amplifies the received signals at the receiver, and then returns to the transmitter through the backward channel for homodyne detection and decoding. We analyze the security of THz-FL-QKD against individual attacks and optimum collective attacks. Numerical simulations show that THz-FL-QKD is capable of a 50 Mbps SKR at 10 THz frequency in a 200 km inter-satellite wireless link. We expect this work will provide an efficient path to build a high-speed global quantum communication network.

FL-QKD based on optical-THz biphotons generated by spontaneous parametric downconversion in inter-satellite wireless communication: publisher's note.

This publisher's note serves to identify a correction in Appl. Opt.60, 7362 (2021)APOPAI0003-693510.1364/AO.430898.

Continuous-Variable Quantum Secret Sharing Based on Thermal Terahertz Sources in Inter-Satellite Wireless Links.

We propose a continuous-variable quantum secret sharing (CVQSS) scheme based on thermal terahertz (THz) sources in inter-satellite wireless links (THz-CVQSS). In this scheme, firstly, each player locally preforms Gaussian modulation to prepare a thermal THz state, and then couples it into a circulating spatiotemporal mode using a highly asymmetric beam splitter. At the end, the dealer measures the quadrature components of the received spatiotemporal mode through performing the heterodyne detection to share secure keys with all the players of a group. This design enables that the key can be recovered only by the whole group players' knowledge in cooperation and neither a single player nor any subset of the players in the group can recover the key correctly. We analyze both the security and the performance of THz-CVQSS in inter-satellite links. Results show that a long-distance inter-satellite THz-CVQSS scheme with multiple players is feasible. This work will provide an effective way for building an inter-satellite quantum communication network.

Plant Sample Preparation for Nucleoside/Nucleotide Content Measurement with An HPLC-MS/MS.

Nucleosides/nucleotides are building blocks of nucleic acids, parts of cosubstrates and coenzymes, cell signaling molecules, and energy carriers, which are involved in many cell activities. Here, we describe a rapid and reliable method for the absolute qualification of nucleoside/nucleotide contents in plants. Briefly, 100 mg of homogenized plant material was extracted with 1 mL of extraction buffer (methanol, acetonitrile, and water at a ratio of 2:2:1). Later, the sample was concentrated five times in a freeze dryer and then injected into an HPLC-MS/MS. Nucleotides were separated on a porous graphitic carbon (PGC) column and nucleosides were separated on a C18 column. The mass transitions of each nucleoside and nucleotide were monitored by mass spectrometry. The contents of the nucleosides and nucleotides were quantified against their external standards (ESTDs). Using this method, therefore, researchers can easily quantify nucleosides/nucleotides in different plants.

γ-Aminobutyric Acid Suppresses Iron Transportation from Roots to Shoots in Rice Seedlings by Inducing Aerenchyma Formation.

γ-Aminobutyric acid (GABA) is a widely distributed non-protein amino acid mediated the regulation of nitrate uptake and Al3+ tolerance in plants. However, there are few reports about the involvement of GABA in the regulation of iron (Fe) acquisition and translocation. Here, we show that GABA regulates Fe homeostasis in rice seedlings. Exogenous GABA decreased the chlorophyll concentration in leaves, with or without Fe supply. Over-expression of glutamate decarboxylase (GAD) gene, coding a crucial enzyme of GABA production, elevated endogenous GABA content and caused more leaf chlorosis than wild type (Nipponbare). GABA inhibited Fe transportation from roots to shoots and GABA application elevated the expression levels of Fe deficiency (FD)-related genes under conditions of Fe-sufficiency (FS), suggesting that GABA is a regulator of Fe translocation. Using Perls' blue staining, we found that more ferric iron (Fe3+) was deposited in the epidermal cells of roots treated with GABA compared with control roots. Anatomic section analysis showed that GABA treatment induced more aerenchyma formation compared with the control. Aerenchyma facilitated the oxidization of soluble ferrous iron (Fe2+) into insoluble Fe3+, resulted in Fe precipitation in the epidermis, and inhibited the transportation of Fe from roots to shoots.