Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective:To explore the effect of minimally invasivetransforaminal lumbar interbody fusion (MIS-TLIF) on lumbar multifidus muscle using MRI techniqueandits clinical significance.Methods:From September 2016 to July 2019, 23 patients who underwent MIS-TLIF surgery for unilateral symptomatic disc herniation in unilateral segments (L 3,4, L 4,5, L 5S 1) of Qingdao University Affiliated Hospital were studied. Their lumbar MR examination was performed 1 week before surgery, and 3 and 6 months after surgery. The axial section of multifidus muscle cross section area (AxCSA) was measured on the axial T2WI image of each intervertebral disc level before and after the operation. The ratio of long and short lines (RLS) was calculated, andthe ratio of axial section of muscle fat infiltration cross section area (FLSA) and AxCSAwasrecorded as FLSA/AxCSA. The changes of various indexes of multifidus muscle in the affected side and the healthy side of the lumbar spine before and after the operation were compared, and the effect of the MIS-TLIF procedure on the morphology of the multifidus muscle was observed. Magnetic resonance spectroscopy (MRS) measurements of the muscle cross-section of the affected side were performed before and 6 months after the operation. The integral value of intracellular lipid (IMCL) and extracellular lipid (EMCL) of 1H spectrum muscle cells was compared, while the degree of fat infiltration was measured. Results:Patients with single-segment lumbar disc herniation had larger AxCSAin the healthy side than the affected side before surgery in surgical level ( t=6.611, P<0.05), and the muscle AxCSAin the healthy side was larger than the affected side in non-surgical levels ( t=-6.682, P<0.05), both suggested preoperative muscle volume advantage in the healthy side; no difference in bilateral AxCSA at 3 months was found after surgeryin surgical levels ( t=0.197, P> 0.05)and non-surgical levels ( t=-1.631, P> 0.05), which suggested bilateral muscle volume equal advantageat short-term follow-up. The FLSA/AxCSA of affected segment before and after 3 months was 9.5%±3.8% and 8.7%±1.5%, and the difference was statistically significant ( t=3.163, P<0.05); the RLS of affected segment before and after 3 months was 3.3%±0.24% and 2.7%±0.83%, and the difference was statistically significant ( t=3.42, P<0.05). The medians of EMCL/IMCL before and after 6 months of MRS were 2.010 and 1.475, respectively, and EMCL decreased after 6 months ( Z=0.48, P<0.05). Conclusion:Patients with single-segment lumbar disc herniation have different morphology of bilateral multifidus muscle before surgery. MIS-TLIF has little effect on the multifidus muscle of the surgical side. MIS-TLIF significantly reduces extracellular lipid accumulation, promotes intracellular transfer, and increases intracellular fat metabolism. Its retention of muscle attachment points and limited fixation can also reshape compensatory muscle atrophy.

BACKGROUNDPhotodynamic therapy (PDT) has been recommended as a main treatment for idiopathic choroidal neovascularization (I-CNV). But the visual results of PDT were inconsistent and variable, and PDT may bring severe damage to the retinal pigment epithelium and choriocapillaries. In recent years, intravitreal ranibizumab therapy, showing favorable visual outcomes, has developed as an advanced treatment for choroidal neovascularization (CNV). Although both methods have been reported to be effective in treating I-CNV, there is no detailed comparative report between the two methods. This study aimed to compare visual outcomes, retinal and choroidal thickness between intravitreal ranibizumab therapy and PDT in the treatment of I-CNV, and investigate the correlation of visual outcomes with retinal and choroidal thickness in each of the two groups.

METHODSThirty-seven eyes of 37 patients with I-CNV were involved in this study; 19 eyes were treated with intravitreal ranibizumab therapy and 18 eyes were treated with PDT. The best corrected visual acuity (BCVA) was recorded before and at each follow-up visit after treatments (logMAR). Enhanced-depth imaging optical coherence tomography (EDI-OCT) was used to evaluate the retinal structural changes, and to measure central retinal thickness (CRT) and central choroidal thickness (CCT).

RESULTSMean BCVA was 0.64 ± 0.27 in PDT group and 0.69 ± 0.22 in ranibizumab group at baseline (P = 0.55). When compared with the baseline, mean BCVA in PDT group was improved significantly at 3-month after PDT (0.41 ± 0.16, P = 0.002), then changed little (0.42±0.25 at 12-month, P = 0.88). Whereas mean BCVA in Ranibizumab group was improved significantly at each follow-up visit. It improved much more obviously in the first month and then remained stable. The mean BCVA in the ranibizumab group was significantly better at each follow-up visit than that in PDT (P < 0.05). When compared with the baseline, mean CRT in PDT group decreased significantly since 3-month visit, whereas mean CRT in ranibizumab group decreased significantly from 1-month visit. Mean CRT at 1-month and 3-month decreased much more in ranibizumab group than that in PDT group, almost in the same period as BCVA improving. When compared with the baseline, mean CCT did not change significantly at each follow-up visit in each group (P > 0.05). The CCT difference was not statistically significant between the two groups at each same time visit (P > 0.05). Mean BCVA was correlated with CRT, but was not correlated with CCT.

CONCLUSIONSBoth intravitreal ranibizumab therapy and PDT are effective for the treatment of I-CNV. It is obvious that ranibizumab therapy is significantly superior to PDT in improving BCVA and decreasing CRT. CRT decreases much more rapidly in ranibizumab group than in PDT group, simultaneously with visual improvement. CRT reduction has significant correlation with the visual outcomes in the recovery of I-CNV, whereas BCVA prognosis may have no correlation with CCT. CCT is not changed significantly after each of the treatments. Both PDT and ranibizumab therapy may have no significant effect on choroid.

Antibodies, Monoclonal, Humanized ; administration & dosage ; therapeutic use ; Choroidal Neovascularization ; drug therapy ; therapy ; Female ; Humans ; Intravitreal Injections ; Male ; Photochemotherapy ; methods ; Ranibizumab ; Retina ; drug effects ; pathology ; Visual Acuity ; drug effects

BACKGROUNDIt is very common for professional divers to have damage on the retinas. Severe retinal lesions can profoundly affect athletes' training efficacy and their daily lives. At present, it is not clear if there is effective preventive action. Thus, in our study, we continuously tracked the ocular changes in athletes and closely monitored the risk factors associated with retinal detachment. Also, we analyzed possible interventions, their associated factors, and efficacies for timely preventions to protect the retina from damage in professional divers.

METHODSBetween 2009 and 2012, a total of 39 professional divers enrolled in follow-up management. The conducted examinations included ocular examination, record screening on retinal lesion, monitoring best-corrected visual acuity, and checking intraocular pressure (IOP) and the scope of retinal lesion. The management included optimizing training methods, taking customized follow-up based on different retinal lesions, laser treatments for definite cases of retinal tear, retinal degeneration caused by retinal layer thinning or vitreous traction, and observing the changes in the scope of retinopathy.

RESULTSEvery year, the percentage of divers who have various degrees of retinal lesions is between 43.3% and 56.2%. During the 4 years, there were no statistically significant differences in divers' best-corrected visual acuity and retinal lesions. There were also no statistically significant differences between male and female athletes. However, there were statistically significant differences in IOP during these years. Moreover there were statistically significant differences in IOP and the scope of retinal lesions between platform divers and springboard divers.

CONCLUSIONSOur management of retinal lesions could be effective to prevent severe retinopathy in professional divers. At the same time, platform divers are more likely to have retinal lesions than springboard divers.

Adolescent ; Diving ; injuries ; Female ; Humans ; Male ; Retina ; pathology ; Retinal Detachment ; etiology ; Retinal Diseases ; therapy

Viburnum odoratissimum is a folk medicinal plant, it can dredge the meridian passage and contains mainly diterpenes, triterpenes, flavonoids, sesquiterpenes, lignans, coumarin glycosides, etc. Vibsanin-type diterpenoids are the characteristic compounds of V. odoratissimum, and are divided into eleven-membered ring, seven-membered ring, and rearrangement-type. Vibsanin B, vibsanin C and neovibsanin A are the representative compounds of the three subtypes of vibsanin-type diterpenoids respectively. V. odoratissimum has cytotoxic activity, antibacterial activity, fish piscicidal activity and activity of inhibiting the growth of plants, Cytotoxic activity is the main biological activity.

OBJECTIVETo investigate the chemical constituents from the ethanol extract of the stems of Lonicera japonica.

METHODThe constituents were isolated and purified by repeated column chromatography on silica gel, Sephadex LH-20 and MCI HP-20. Their structures were identified by phsicochemical properties and spectroscopic analysis.

RESULTThirteen compounds were isolated and identified as protocatechuic acid (1), caffeic acid (2), macranthoin G (3), esculetin (4), luteolin (5), quercetin (6), apigenin (7), luteolin-7-O-beta-D-glucopyranoside (8), isorhamnetin-7-O-beta-D-glucopyranoside (9), diosmetin-7-O-beta-D-glucopyranoside (10), rhoifolin (11), lonicerin (12), hydnocarpin D (13).

CONCLUSIONCompound 4, 7, 9-11 were isolated from this plant for the first time, while compound 13 was first reported flavanolignan from this genus Lonicera.

Luteolin ; chemistry ; Plant Extracts ; analysis ; isolation & purification ; Plant Stems ; chemistry