Objective: This study aimed to assess the presence of novel coronavirus in tears and conjunctival secretions of SARS-CoV-2-infected patients.Methods: A prospective interventional case series study was performed, and 30 confirmed novel coronavirus pneumonia (NCP) patients were selected at the First Affiliated Hospital of Zhejiang University from 26 January 2020 to 9 February 2020. At an interval of 2 to 3 days, tear and conjunctival secretions were collected twice with disposable sampling swabs for reverse-transcription polymerase chain reaction (RT-PCR) assay.Results: Twenty-one common-type and nine severe-type NCP patients were enrolled. Two samples of tear and conjunctival secretions were obtained from the only one patient with conjunctivitis yielded positive RT-PCR results. Fifty-eight samples from other patents were all negative. Conclusion:We speculate that SARS-CoV-2 may be detected in the tears and conjunctival secretions in NCP patients with conjunctivitis.

The expression of Programmed cell Death Ligand 1 (PD-L1) is observed in many malignant tumors and is associated with poor prognosis including Gastric Cancer (GC). The relationship between PD-L1 expression and prognosis, however, is controversial in GC. This paper purports to use a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in GC. For this study, the following databases were searched for articles published from June 2003 until February 2017: PubMed, EBSCO, Web of Science and Cochrane Library. The baseline information extracted were: authors, year of publication, country where the study was performed, study design, sample size, follow-up time, baseline characteristics of the study population, pathologic data, overall survival (OS). A total of 15 eligible studies covering 3291 patients were selected for a meta-analysis based on specified inclusion and exclusion criteria. The analysis showed that the expression level of PD-L1 was associated with the overall survival in GC (Hazard Ratio, HR = 1.46, 95%CI = 1.08–1.98, P = 0.01, random-effect). In addition to the above, subgroup analysis showed that GC patients with deeper tumor infiltration, positive lymph-node metastasis, positive venous invasion, Epstein-Barr virus infection positive (EBV+), Microsatellite Instability (MSI) are more likely to expression PD-L1. The results of this meta-analysis suggest that GC patients, specifically EBV+ and MSI, may be prime candidates for PD-1 directed therapy. These findings support anti-PD-L1/PD-1 antibodies as a kind of immunotherapy which is promising for GC.

The effectiveness of in vitro primer elongation reactions catalyzed by human bypass DNA polymerases (hDinB1), pol (hRad30A), pol (hRad30B), and yeast pol (Rev3 and Rev7) in site-specifically modified template oligonucleotide strands were studied in vitro. The templates contained single bulky lesions derived from the trans-addition of the mutagenic (؉)-or (؊)-enantiomers of r7,t8-dihydroxy-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (a metabolite of the environmental carcinogen benzo[a]pyrene), to the exocyclic amino groups of guanine or adenine in oligonucleotide templates 33, or more, bases long. In "running start" primer extension reactions, pol effectively bypassed both the stereoisomeric (؉)-and (؊)-trans-guanine adducts but not the analogous adenine adducts. In sharp contrast, pol , which exhibits considerable sequence homology with pol (both belong to the group of Y family polymerases), is partially blocked by the guanine adducts and the (؊)-trans-adenine adduct, although the stereoisomeric (؉)-trans-adenine adduct is more successfully bypassed. Neither pol nor pol , either alone or in combination, were effective in trans-lesion synthesis past the same adducts. In all cases, the fidelity of insertion is dependent on adduct stereochemistry and structure. Generally, error-free nucleotide insertion opposite the lesions tends to depend more on adduct stereochemistry than error-prone insertion. None of the polymerases tested are a universal bypass polymerase for the stereoisomeric bulky polycyclic aromatic hydrocarbon-DNA adducts derived from anti-BPDE.Several new prokaryotic and eukaryotic DNA polymerases (pol) 1 involved in trans-lesional synthesis have been recently identified (reviewed in Refs. 1-5). The functional characteristics of the UmuC/DinB/Rev1p/Rad30 DNA polymerases belonging to the Y family of DNA polymerases (5) have been extensively investigated (6 -11). These polymerases are able to bypass a variety of DNA lesions in vitro (8,(12)(13)(14)(15)(16)(17)(18)(19)(20) that are known to block replication catalyzed by "classical" polymerases such as pol ␣, pol ␤, phage T7, the Klenow fragment of pol I from Escherichia coli, and human immunodeficiency virusreverse transcriptase, etc. (see Refs. 21-18 for example).The efficiencies and fidelities of trans-lesion synthesis catalyzed by Y family polymerases vary significantly among the different subfamilies and also depend remarkably on the type of DNA damage. Purified human pol (DinB1, 870 amino acids in size) efficiently bypasses (Ϫ)-trans-[BP]-N 2 -dG adducts (bulky lesions derived from the binding of the mutagen r7,t8-dihydroxy-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene ((ϩ)-or (Ϫ)-anti-BPDE) to the exocyclic amino groups of guanine and adenine residues in DNA (Scheme 1) with the insertion of a C opposite the lesion (12). A truncated form of pol , a 560-amino acid form pol (⌬C), missing motifs VIIa and VIIb and obtained from a baculovirus expression system, also bypasses the (ϩ)- trans-[BP]-N2 -dG adduct (29). Human pol also bypasses 8-oxo-dG lesio...

DNA polymerase (Pol, xeroderma pigmentosum variant, or Rad30) plays an important role in an errorfree response to unrepaired UV damage during replication. It faithfully synthesizes DNA opposite a thyminethymine cis-syn-cyclobutane dimer. We have purified the yeast Pol and studied its lesion bypass activity in vitro with various types of DNA damage. The yeast Pol lacked a nuclease or a proofreading activity. It efficiently bypassed 8-oxoguanine, incorporating C, A, and G opposite the lesion with a relative efficiency of ϳ100: 56:14, respectively. The yeast Pol efficiently incorporated a C opposite an acetylaminofluorene-modified G, and efficiently inserted a G or less frequently an A opposite an apurinic/apyrimidinic (AP) site but was unable to extend the DNA synthesis further in both cases. However, some continued DNA synthesis was observed in the presence of the yeast Pol following the Pol action opposite an AP site, achieving true lesion bypass. In contrast, the yeast Pol␣ was able to bypass efficiently a template AP site, predominantly incorporating an A residue opposite the lesion. These results suggest that other than UV damage, Pol may also play a role in bypassing additional DNA lesions, some of which can be error-prone.

DNA polymerase (Pol) is a newly discovered member of the polymerase X family with unknown cellular function. The understanding of Pol function should be facilitated by an understanding of its biochemical activities. By using purified human Pol for biochemical analyses, we discovered the lesion bypass activities of this polymerase in response to several types of DNA damage. When it encountered a template 8-oxoguanine, abasic site, or 1,N 6 -ethenoadenine, purified human Pol efficiently bypassed the lesion. Even bulky DNA adducts such as N-2-acetylaminofluorene-adducted guanine, (؉)-and (؊)-trans-anti-benzo[a]pyrene-N 2 -dG were unable to block the polymerase activity of human Pol. Bypass of these simple base damage and bulky adducts was predominantly achieved by human Pol through a deletion mechanism. The Pol specificity of nucleotide incorporation indicates that the deletion resulted from primer realignment before translesion synthesis. Purified human Pol also effectively bypassed a template cis-syn TT dimer. However, this bypass was achieved in a mainly error-free manner with AA incorporation opposite the TT dimer. These results provide new insights into the biochemistry of human Pol and show that efficient translesion synthesis activity is not strictly confined to the Y family polymerases.DNA polymerase (Pol) 1 is a newly discovered member of the X family polymerases (1, 2). Additional members in this family include Pol␤, Pol, and terminal deoxynucleotidyltransferase (1-3). During base excision repair in higher eukaryotes, Pol␤ is a major repair synthesis polymerase (4 -6). Terminal deoxynucleotidyltransferase catalyzes nucleotide additions to DNA in a template-independent manner (7,8). This enzyme functions during V(D)J recombination of the immunoglobulin genes and T-cell receptor genes and is restricted to lymphoid tissues (7-9). Cellular functions of Pol and Pol have not been clearly defined.Although the biochemical activities of the X family DNA polymerases appear to be quite diverse, all of the Y family DNA polymerases share a common biochemical activity: synthesis opposite DNA lesions (reviewed in Refs. 10 -13). In eukaryotes, the Y family consists of REV1 and DNA polymerases , , and (14). Thus, it is generally believed that a major function of the Y family DNA polymerases is to copy damaged sites of DNA during replication, a cellular process referred to as lesion bypass or translesion synthesis. Genetic studies indicate that REV1 (15-18) and are indeed involved in lesion bypass in cells. Lesion bypass can be error-free as a result of insertion of the correct nucleotide opposite the lesion or errorprone as the result of insertion of an incorrect nucleotide opposite the lesion. Both error-free and error-prone nucleotide insertions have been observed with the Y family polymerases depending on the specific lesion and the specific polymerase (reviewed in Refs. 10 -12).Biochemical studies of purified human Pol have uncovered a unique property that has never been observed with any other polymerases studied ...

In the yeast Saccharomyces cerevisiae, DNA polymerase zeta (Polzeta) is required in a major lesion bypass pathway. To help understand the role of Polzeta in lesion bypass, we have performed in vitro biochemical analyses of this polymerase in response to several DNA lesions. Purified yeast Polzeta performed limited translesion synthesis opposite a template TT (6-4) photoproduct, incorporating A or T with similar efficiencies (and less frequently G) opposite the 3' T, and predominantly A opposite the 5' T. Purified yeast Polzeta predominantly incorporated a G opposite an acetylaminofluorene (AAF)-adducted guanine. The lesion, however, significantly inhibited subsequent extension. Furthermore, yeast Polzeta catalyzed extension DNA synthesis from primers annealed opposite the AAF-guanine and the 3' T of the TT (6-4) photoproduct with varying efficiencies. Extension synthesis was more efficient when A or C was opposite the AAF-guanine, and when G was opposite the 3' T of the TT (6-4) photoproduct. In contrast, the 3' T of a cis-syn TT dimer completely blocked purified yeast Polzeta, whereas the 5' T was readily bypassed. These results support the following dual-function model of Polzeta. First, Polzeta catalyzes nucleotide incorporation opposite AAF-guanine and TT (6-4) photoproduct with a limited efficiency. Secondly, more efficient bypass of these lesions may require nucleotide incorporation by other DNA polymerases followed by extension DNA synthesis by Polzeta.

Adrenocorticotropic hormone (ACTH), and α-, β-, and γ-melanocyte-stimulating hormones (α-, β-, γ-MSH), collectively known as melanocortins, together with their receptors (melanocortin receptors), are components of an ancient modulatory system. The clinical use of ACTH in the treatment of rheumatoid arthritis started in 1949, originally thought that the anti-inflammatory action was through hypothalamus-pituitary-adrenal axis and glucocorticoid-dependent. Subsequent decades have witnessed extensive attempts in unraveling the physiology and pharmacology of the melanocortin system. It is now known that ACTH, together with α-, β-, and γ-MSHs, also possess glucocorticoid-independent anti-inflammatory and immunomodulatory effects by activating the melanocortin receptors expressed in the brain or peripheral immune cells. This review will briefly introduce the melanocortin system and highlight the action of melanocortins in the regulation of immune functions from in vitro, in vivo, preclinical, and clinical studies. The potential therapeutic use of melanocortins are also summarized.

Background: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, many studies have reported the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the conjunctival sac of patients infected with this virus, with several patients displaying symptoms of viral conjunctivitis. However, to our best knowledge, there is no in-depth report on the course of patients with COVID-19 complicated by relapsing viral conjunctivitis or keratoconjunctivitis. Case presentation: A 53-year-old man confirmed with COVID-19 developed symptoms of viral conjunctivitis in the left eye approximately 10 days after the onset of COVID-19. The results of a nucleic acid test were positive for SARS-CoV-2 in the conjunctival sac of the left eye. The symptoms were relieved 6 days after treatment. However, the patient was subsequently diagnosed with viral keratoconjunctivitis in both eyes 5 days after the symptoms in the left eye were satisfactorily relieved. The disease progressed rapidly, with spot staining observed at the periphery of the corneal epithelium. Although SARS-CoV-2 could not be detected in conjunctival secretions, the levels of inflammatory factors, such as interleukin-6, were increased in both eyes. Both eyes were treated with glucocorticoids, and symptoms were controlled within 5 days. There was no recurrence. Conclusions: In this case report, the pathogenesis, clinical manifestations, treatment, and outcome of a case with COVID-19 complicated by relapsing viral keratoconjunctivitis is described, and the involvement of topical cytokine surge in the pathogenesis of COVID-19 as it relates to viral keratoconjunctivitis is reported.