Structure-guided antibody cocktail for prevention and treatment of COVID-19.

Development of effective therapeutics for mitigating the COVID-19 pandemic is a pressing global need. Neutralizing antibodies are known to be effective antivirals, as they can be rapidly deployed to prevent disease progression and can accelerate patient recovery without the need for fully developed host immunity. Here, we report the generation and characterization of a series of chimeric antibodies against the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Some of these antibodies exhibit exceptionally potent neutralization activities in vitro and in vivo, and the most potent of our antibodies target three distinct non-overlapping epitopes within the RBD. Cryo-electron microscopy analyses of two highly potent antibodies in complex with the SARS-CoV-2 spike protein suggested they may be particularly useful when combined in a cocktail therapy. The efficacy of this antibody cocktail was confirmed in SARS-CoV-2-infected mouse and hamster models as prophylactic and post-infection treatments. With the emergence of more contagious variants of SARS-CoV-2, cocktail antibody therapies hold great promise to control disease and prevent drug resistance.

SIN3-HDAC complex-associated factor, a chromatin remodelling gene located in the 12p amplicon, is a potential germ cell tumour-specific oncogene.

A genetic hallmark of malignant germ cell tumours (GCTs) is isochromosome 12p, but oncogenes located in 12p that are specifically expressed in GCT have not yet been identified. SIN3-HDAC complex-associated factor (SINHCAF) is a subunit of the Sin3/histone deacetylase (HDAC) complex, and it defines a Sin3a-Hdac complex variant that is required for the self-renewal of mouse embryonic stem cells. This study demonstrated that SINHCAF is expressed in a vast majority of malignant GCTs and is rarely expressed in somatic malignancy. Fluorescence in situ hybridisation revealed SINHCAF amplification in malignant GCTs. SINHCAF silencing using shRNA reduced anchorage-dependent cell proliferation and tumoursphere formation and inhibited tumour cell migration and invasion in GCT cell lines. Moreover, in the GCT cell line NTERA2/D1, SINHCAF silencing inhibited the expression of genes associated with embryonic stem cells and induced the expression of genes associated with neuronal and white fat cell differentiation. Compared with somatic cell lines, GCT cell lines were more susceptible to HDAC inhibitor treatment. Thus, we identified SINHCAF to be a potential oncogene located in the amplicon of chromosome 12p and showed that SINHCAF was specifically expressed in malignant GCTs. HDAC inhibitor treatment may counteract the oncogenic activity of SINHCAF and is a promising therapeutic approach for GCTs. © 2022 The Pathological Society of Great Britain and Ireland.

Authenticated Semi-Quantum Key Distribution Protocol Based on W States.

In 2019, Wen et al. proposed authenticated semi-quantum key distribution (ASQKD) for identity and message using the teleportation of W states and GHZ-like states without pre-shared keys. However, the ASQKD protocol presents a vital issue in the teleportation of W states owing to its inappropriate design. Bob recovers the teleported W states without obtaining the position of the corresponding photons and then returns the recovered photons back to Alice. Hence, the teleportation of W states in Wen et al.'s ASQKD protocol was malfunctioning. Moreover, Wen et al.'s ASQKD protocol requires quantum memory, which strongly disobeys the definition of semi-quantum proposed by Boyer et al. Therefore, in this study, we discover the flaws of Wen et al.'s ASQKD protocol and propose an authenticated semi-quantum key distribution protocol. When compared to Wen et al.'s ASQKD protocol, the proposed ASQKD protocol has the following advantages: legal semi-quantum environment (i.e., does not require quantum memory), reduced quantum hardware requirement (i.e., based only on W states), does not involve classical cryptography (i.e., the hash function), and provided 1.6 times higher qubit efficiency.

Cryptanalysis of a Semi-Quantum Bi-Signature Scheme Based on W States.

Recently, Zhao et al. proposed a semi-quantum bi-signature (SQBS) scheme based on W states with two quantum signers and just one classical verifier. In this study, we highlight three security issues with Zhao et al.'s SQBS scheme. In Zhao et al.'s SQBS protocol, an insider attacker can perform an impersonation attack in the verification phase and an impersonation attack in the signature phase to capture the private key. In addition, an eavesdropper can perform a man-in-the-middle attack to obtain all of the signer's secret information. All of the above three attacks can pass the eavesdropping check. Without considering these security issues, the SQBS protocol could fail to ensure the signer's secret information.

Synthesis, Characterization, and Catalytic Application of Palladium Complexes Containing Indolyl-NNN-Type Ligands.

In this study, a series of N-heterocyclic indolyl ligand precursors 2-Py-Py-IndH, 2-Py-Pz-IndH, 2-Py-7-Py-IndH, 2-Py-7-Pz-IndH, and 2-Ox-7-Py-IndH (L1H-L5H) were prepared. The treatment of ligand precursors with 1 equivalent of palladium acetate affords palladium complexes 1-5. All ligand precursors and palladium complexes were characterized by NMR spectroscopy and elemental analysis. The molecular structures of complexes 3 and 5 were determined by single crystal X-ray diffraction techniques. The application of those palladium complexes 1-5 to the Suzuki reaction with aryl halide substrates was examined.

[Impact of the waist circumference change on new onset of diabetes in the population with impaired fasting glucose].

OBJECTIVE: To explore the impact of the waist circumference change on new onset diabetes (NOD) in the impaired fasting glucose (IFG) population. METHODS: A total of 12 657 subjects who took part in the health examination from 2006 to 2007 and from 2010 to 2011 from the employees of Kailuan Group and met the inclusion criteria were selected as the observation cohort.Of the 12 657 subjects, 10 697 were male, 1960 were female, with age of (49.9 ± 11.3) years old. According to the baseline waist circumference (WC) measurements and its quartile in the health examinations during 2006 to 2007, the observation population was divided into four groups (first, second, third and the fourth quartile groups) . Multiple logistic regression analysis was used to test the relation between the increasing of WC and NOD. RESULTS: The incidences in the IFG population of NOD were 4.27% (1884/12 657) in the total population;4.25% (1581/10 697) in male and 4.44% (303/1960) in females, respectively (P < 0.05) . Along with increasing WC in the 4 quartile groups, the incidences of NOD was progressively increased, which were 2.19% (235/3083) , 3.07% (333/3114) , 4.47% (473/3037) and 7.08% (843/3423) , respectively;2.34% (213/2626) , 3.06% (282/2645) , 4.37% (393/2582), 7.00% (693/2844) in males and 1.38% (22/457) , 3.12% (51/469) , 5.05% (80/455) , 7.45% (150/579) in female (P < 0.05) . Multiple logistic regression analysis showed that compared with the first quartile group, the second, third and fourth quartile group had increased risk of NOD after adjusting for age, gender and other risk factors, the OR (95%CI) values were 1.38(1.13-1.68), 1.79 (1.47-2.09) and 3.10 (2.57-3.75), respectively. CONCLUSION: The incidence of NOD in the IFG population increased as the WC increased.

Encryption chain based on measurement result and its applications on semi-quantum key distribution protocol.

This study proposes a new encoding method, also known as an encryption chain based on the measurement result. Then, using the encryption chain to propose a unitary-operation-based semi-quantum key distribution protocol (SQKD) protocol. In the existing SQKD protocols, semi-quantum environments adopt a round-trip transmission strategy. In round-trip transmission, the classical participant must resend the received photons to the quantum participant after implementing local operations. Therefore, round-trip transmissions are vulnerable to Trojan horse attacks. Hence, the classical participant must be equipped with a photon number splitter and an optical wavelength filter device against Trojan horse attacks. This is illogical for semi-quantum environments because the burden on the classical participant is significantly increased as it involves the prevention of Trojan horse attacks. The proposed SQKD protocol is congenitally immune to Trojan horse attacks and involves no extra hardware because it is designed based on a one-way transmission as opposed to a round-trip transmission. When compared to the existing SQKD protocols, the proposed SQKD protocol provides the best qubit efficiency, and classical participants only require two quantum capabilities, which enhance its practicability. Moreover, the proposed SQKD protocol is free from collective attacks, Trojan horse attacks, and intercept-resend attacks. Thus, the proposed scheme is more efficient and practical than the existing SQKD protocols.

Lightweight mediated semi-quantum key distribution protocol with a dishonest third party based on Bell states.

The mediated semi-quantum key distribution (MSQKD) protocol is an important research issue that lets two classical participants share secret keys securely between each other with the help of a third party (TP). However, in the existing MSQKD protocols, there are two improvable issues, namely (1) the classical participants must be equipped with expensive detectors to avoid Trojan horse attacks and (2) the trustworthiness level of TP must be honest. To the best of our knowledge, none of the existing MSQKD protocols can resolve both these issues. Therefore, this study takes Bell states as the quantum resource to propose a MSQKD protocol, in which the classical participants do not need a Trojan horse detector and the TP is dishonest. Furthermore, the proposed protocol is shown to be secure against well-known attacks and the classical participants only need two quantum capabilities. Therefore, in comparison to the existing MSQKD protocols, the proposed protocol is better practical.

Identification of gene expression models for laryngeal squamous cell carcinoma using co-expression network analysis.

One of the most common head and neck cancers is laryngeal squamous cell carcinoma (LSCC). LSCC exhibits high mortality rates and has a poor prognosis. The molecular mechanisms leading to the development and progression of LSCC are not entirely clear despite genetic and therapeutic advances and increased survival rates. In this study, a total of 116 differentially expressed genes (DEGs), including 11 upregulated genes and 105 downregulated genes, were screened from LSCC samples and compared with adjacent noncancerous. Statistically significant differences (log 2-fold difference > 0.5 and adjusted P-value < .05) were found in this study in the expression between tumor and nontumor larynx tissue samples. Nine cancer hub genes were found to have a high predictive power to distinguish between tumor and nontumor larynx tissue samples. Interestingly, they also appear to contribute to the progression of LSCC and malignancy via the Jak-STAT signaling pathway and focal adhesion. The model could separate patients into high-risk and low-risk groups successfully when only using the expression level of mRNA signatures. A total of 4 modules (blue, gray, turquoise, and yellow) were screened for the DEGs in the weighted co-expression network. The blue model includes cancer-specific pathways such as pancreatic cancer, bladder cancer, nonsmall cell lung cancer, colorectal cancer, glioma, Hippo signaling pathway, melanoma, chronic myeloid leukemia, prostate cancer, and proteoglycans in cancer. Endocrine resistance (CCND1, RAF1, RB1, and SMAD2) and Hippo signaling pathway (CCND1, LATS1, SMAD2, and TP53BP2) could be of importance in LSCC, because they had high connectivity degrees in the blue module. Results from this study provide a powerful biomarker discovery platform to increase understanding of the progression of LSCC and to reveal potential therapeutic targets in the treatment of LSCC. Improved monitoring of LSCC and resulting improvement of treatment of LSCC might result from this information.

Z-palatoplasty and tongue radiofrequency for patients with small tonsils.

OBJECTIVE: To explore the feasibility and efficacy of Z-palatoplasty for the management of severe obstructive sleep apnea-hypopnea syndrome in patients with tonsils. STUDY DESIGN: Case series and chart review. SETTING: University hospital. METHODS: Z-palatoplasty and coblation channeling of the tongue were performed in 36 patients with body mass index <40 kg/m(2) and size 1 or 2 tonsils. All patients' tonsils were preserved. Follow-up continued for at least 1 year. Success was defined as a postoperative apnea-hypopnea index <15 events per hour and at least 50% less than the preoperative value. RESULTS: The surgical success rate was 58.3% (21/36 patients). Furthermore, 66.7% (24/36 patients) had a ≥ 50% reduction in the apnea-hypopnea index to less than 20 episodes per hour. There were statistically significant differences in preoperative nadir oxygen saturation, percentage of time with oxygen saturation less than 90%, microarousal index, and Friedman tongue position between those who responded to surgery and those who did not. Six patients had temporary velopharyngeal insufficiency. After 3 months, all the patients had normal deglutition. No major perioperative complications occurred. CONCLUSION: Our findings suggest that Z-palatoplasty can improve disease-specific quality of life and sleep apnea symptoms in patients with obstructive sleep apnea-hypopnea syndrome and size 1 or 2 tonsils.

Molecular cloning and sequence analysis of ussurin, a new metalloproteinases/disintegrin from Gloydius ussuriensis.

The metalloproteinases/disintegrins in the snake venom act as platelet aggregation inhibitor by an antagonism against integrin on platelet through its RGD sequence and may play other important role in cell-cell fusion, cell matrix interaction and other cellular function. Ussurin is a new metalloproteinase/disintegrin that was cloned from Gloydius ussuriensis. Poly (A+) RNA was purified from the total RNA preparation from venom gland of a single G. ussuriensis using the poly (A+) tract-mRNA isolation system. A cDNA library was constructed with the SMART PCR cDNA library construction kit. The cDNA library was screened and the positive clones were selected. The full-length cDNA of Ussurin was obtained. The cDNA encoding the Ussurin precursor has a 51bp 5'-UTR, the open reading frame of Ussurin and a 490 bp 3'-UTR, the open reading frame of Ussurin cDNA nucleotide sequence is 1434 bp and codes for 478 amino acids with a predicted molecular mass of 53.2 kD and an isoelectric point of 5.37. There is no potential N-glycosylation site in the deduced sequence region. Its deduced amino acid sequence consists of four region, a signal sequence of 18 amino acid residues, a zymogen pro-peptide of 171 amino acid residues with a cysteine switch motif (PK-MCGVT) in it, a central metalloproteinase domain of 201 amino acid residues containing a conserved zinc-chelating sequence (HEXXHXXGXXH) and a methionine-turn CIM involving zinc banding also, a space sequence between metalloproteinase domain and disintegrin domain of 15 amino acid residues with a conserved T392, T397, S400, which is specific residues of the P-II snake venom metalloproteinases, a disintegrin domain of 73 amino acid residues with a characteristic RGD region and six-disulfide bonds. Ussurin belongs to P-II class. The cDNA sequence and deduced amino acid sequence of Ussurin precursor were compared with homologous sequence in the GenBank database, the result reveals high degree of homology in sequence and organization pattern of domain with metalloproteinase/disintegrin gene family of other snake species. Compared with the alignment of amino acid sequence of metalloproteinase/disintegrin member, hypervariable regions of this member were revealed, besides they share higher homologous in the zymogen domain. It suggests that the hypervariable regions are the counterparts directly suitable for interacting with different domain of receptors, different receptors or substrates.