Predicting the postoperative intraocular lens position based on IOL Master 700 biometry, compared with results from the anterior segment analysis system.

PURPOSE: Predict intraocular lens position after cataract surgery using the IOL Master 700 and explore the associated ocular parameters compared with the results obtained from the anterior segment analysis system (Sirius, CSO Inc, Florence, Italy). METHODS: A total of 98 patients (106 eyes) were included in the retrospective study. The postoperative intraocular lens position was obtained using the IOL Master 700 and measured using Adobe Illustrator software. Correlation analysis and linear regression analysis were applied to study the correlation between the actual position of the postoperative intraocular lens (ALP) and the ocular parameters. In addition, Bland-Altman consistency analysis was used to compare the consistency between any two among the predicted intraocular lens position (ALPi) obtained using IOL Master 700 biometry, the predicted artificial lens position (ALPs) calculated using the anterior segment analysis system, or the ALP. RESULTS: Ocular parameters, including preoperative anterior chamber depth, lens thickness, axial length, white-to-white, and postoperative refractive error were all correlated with ALP after cataract surgery (P < 0.05) using univariate analysis. However, in multivariate linear regression, only the first three variables were correlated with ALP. Compared with the equation obtained by the anterior segment analysis, the equation from IOL Master 700 biometry provided a better fit. The results of the consistency analysis showed that ALP, ALPi, and ALPs were in good agreement. CONCLUSION: IOL Master 700 biometry can help predict intraocular lens position after surgery, and its accuracy is better than that provided by the anterior segment analysis system.

Topical Administration of Bevacizumab to Facilitate the Functional Filtering Bleb After Trabeculectomy in the Rabbit.

Purpose: To evaluate the effects of bevacizumab in 3 different application methods, subconjunctival injection (SCI), hyaluronic acid retardant (HAR), and eye drop (ED), on attenuating scar formation in the filtering bleb. Methods: Trabeculectomy (TRAB) was performed on New Zealand rabbits. TRAB rabbits were intervened with bevacizumab SCI, HAR, ED, or mitomycin C, respectively. Intraocular pressure (IOP) of 1, 7, 14, and 28 days after TRAB was recorded, and the bleb survival rate was analyzed. Bleb height, area, and vascularization were evaluated using anterior segment optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) at 7, 14 and 28 days after surgery. A histopathology examination of the bleb tissue was performed. The expression levels of vascular endothelial growth factor (VEGF)-A, interleukin (IL)-1α, tumor necrosis factor-alpha (TNF-α), transforming growth factor-ß1 (TGF-ß1), and α-smooth muscle actin (α-SMA) were measured by Western blot. Results: Bevacizumab significantly reduced postoperative IOP and increased the survival of the filtering bleb, especially in the ED group. Less vascularization was shown in the SCI, HAR, and ED groups. Histopathological results showed the fewest levels of scarring and fibrosis in the ED group. The local VEGF-A, IL-1α, and TNF-α expression levels after bevacizumab ED were decreased, combined with suppression of TGF-ß1 and α-SMA. Conclusions: Postoperative use of bevacizumab EDs was an effective application method for improving surgical outcomes after TRAB in rabbits. It might be effective in preventing scarring of the filtering bleb by antivascularization and anti-inflammation.

Inhalable chitosan-based hydrogel as a mucosal adjuvant for hydroxychloroquine in the treatment for SARS-CoV-2 infection in a hamster model.

BACKGROUND: Effective therapy for COVID-19 remains limited. Hydroxychloroquine (HCQ) has been considered, but safety and efficacy concerns remain. Chitosan exhibits antiviral and immunomodulatory effects, yet how the combination of HCQ and chitosan performs in treating COVID-19 is unknown. METHODS: Male Syrian hamsters were inoculated intranasally with standardized stocks of the SARS-CoV-2 virus. Hamsters were allocated to saline (PBS), chitosan oligosaccharide (COS), HCQ, or COS + HCQ groups and received corresponding drugs. On days 1, 7, and 14 post-infection, two animals from each group were euthanized for sample collection. Viral loads were measured in lung homogenates. Biochemistry markers, cytokines, and immunoglobulins were analyzed from hamster sera. HCQ concentrations were compared between the blood, bronchoalveolar lavage, and lung tissues. All groups underwent histopathology exams of the lungs. Additional hamsters were treated with the same drugs to assess for toxicities to the heart and liver. RESULTS: Among all groups, viral loads in the COS + HCQ group were the lowest by day 8. The COS + HCQ group produced the highest interleukin (IL)-6 levels on day 4, and the highest IL-10, IgA and IgG levels on day 8. HCQ concentrations were higher in the COS + HCQ group's lungs than the HCQ group, despite having received half the dose of HCQ. Histopathology demonstrated earlier inflammation resolution and swifter viral clearance in the COS + HCQ group. There was no evidence of cardiac or hepatic injury in hamsters that received HCQ. CONCLUSION: In hamsters infected with the SARS-CoV-2 virus, the combination of intranasal COS and HCQ was associated with increased HCQ absorption in the lungs, more effective immune responses, without increasing the risk of hepatic or cardiac injuries.

Programmed cell death 1 pathway inhibitors improve the overall survival of small cell lung cancer patients with brain metastases.

PURPOSE: The objective of this study was to evaluate the safety and efficacy of immune checkpoint inhibitors in small cell lung cancer patients with brain metastases. METHODS: We retrospectively reviewed the records of small cell lung cancer patients with brain metastases treated with chemotherapy and radiotherapy for brain metastases with or without immune checkpoint inhibitors at our institution from January 2019 to January 2021. Patients were divided into two groups. In Group A, patients received chemotherapy and radiotherapy for brain metastases. In Group B, patients received chemotherapy, radiotherapy for brain metastases and at least four cycles of immunotherapy. Overall survival and intracranial progression-free survival were assessed using Kaplan-Meier estimates and Cox regression models. RESULTS: A total of 282 patients were enrolled in our study. At the end of the study (May 12, 2021), the median overall survival was 13.3 months among 218 patients in Group A and 33.4 months among 64 patients in Group B (hazards ratio [HR] 0.320, 95% confidence interval [CI], 0.189-0.545, P < 0.001). Both univariate and multivariate analyses suggested that two factors were significantly correlated with overall survival: the inclusion of immunotherapy in the regimen and the presence of extracranial metastases. The median intracranial progression-free survival was 6.93 months in Group A and 10.73 months in Group B (HR = 0.540, 95% CI, 0.346-0.841, P = 0.006). The intracranial objective response rate of Group B was greater than that of Group A, but the intracranial disease control rate was similar between the groups. CONCLUSION: Immunotherapy plus chemotherapy and radiotherapy for brain metastases showed promising efficacy for small cell lung cancer patients with brain metastases.

Analyzing the Impact of COVID-19 Lockdowns on Violent Crime.

Existing research suggests that COVID-19 lockdowns tend to contribute to a decrease in overall urban crime rates. Most studies have compared pre-lockdown and post-lockdown periods to lockdown periods in Western cities. Few have touched on the fine variations during lockdowns. Equally rare are intracity studies conducted in China. This study tested the relationship between violent crime and COVID-19 lockdown policies in ZG City in southern China. The distance from the isolation location to the nearest violent crime site, called "the nearest crime distance", is a key variable in this study. Kernel density mapping and the Wilcoxon signed-rank test are used to compare the pre-lockdown and post-lockdown periods to the lockdown period. Panel logistic regression is used to test the fine variations among different stages during the lockdown. The result found an overall decline in violent crime during the lockdown and a bounce-back post-lockdown. Violent crime moved away from the isolation location during the lockdown. This outward spread continued for the first two months after the lifting of the lockdown, suggesting a lasting effect of the lockdown policy. During the lockdown, weekly changes in COVID-19 risk ratings at the district level in ZG City also affected changes in the nearest crime distance. In particular, an increase in the risk rating increased that distance, and a drop in the risk rating decreased that distance. These findings add new results to the literature and could have policy implications for joint crime and pandemic prevention and control.

Isolation and identification of flavonoid-producing endophytic fungi from Loranthus tanakae Franch. & Sav that exhibit antioxidant and antibacterial activities.

AIMS: Loranthus tanakae Franch. & Sav is a medicinal plant that has a variety of pharmacological properties. However, its study is currently limited because of its relative shortage of natural abundance. The objective of this work was to find an alternative resource from this plant that could produce its bioactive ingredients. METHODS AND RESULTS: We isolated endophytic fungi from the twigs of Loranthus tanakae Franch. & Sav and eight flavonoid-producing endophytic fungi were selected. The eight endophytic fungi meeting the criteria were identified as Alternaria tenuissima, Dothiorella gregaria, Penicillium aethiopicum, Nothophoma quercina and Hypoxylon perforatum by morphological and molecular methods. The antioxidant and antibacterial activities of the flavonoid-producing endophytic fungi were investigated in vitro, where Alternaria tenuissima ZP28 and ZM148 demonstrated greater activities than the other six strains. Flavonoids of ZP28 and ZM148 were preliminarily identified by liquid chromatography-mass spectrometry (LC-MS). CONCLUSION: After screening the flavonoid-producing endophytic fungi, Alternaria tenuissima ZP28 and ZM148 were found to have good antioxidant and antibacterial activities. Overall, this study provided new direction and resources for the acquisition of flavonoids. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic fungi are a promising alternative approach for the large-scale production of flavonoids from Loranthus tanakae Franch. & Sav.

A siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has altered the trajectory of the COVID-19 pandemic and raised some uncertainty on the long-term efficiency of vaccine strategy. The development of new therapeutics against a wide range of SARS-CoV-2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS-CoV-2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC50 in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by cotreatment in K18-hACE2-transgenic mice, accompanied by a significant prevention of virus-associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggest that C6G25S provides an alternative and effective approach to combating the COVID-19 pandemic.

Dynamic Changes of the Blood Chemistry in Syrian Hamsters Post-Acute COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes coronavirus disease 2019 (COVID-19). However, the long-term health consequences of COVID-19 are not fully understood. We aimed to determine the long-term lung pathology and blood chemistry changes in Syrian hamsters infected with SARS-CoV-2. Syrian hamsters (Mesocricetus auratus) were inoculated with 105 PFU of SARS-CoV-2, and changes post-infection (pi) were observed for 20 days. On days 5 and 20 pi, the lungs were harvested and processed for pathology and viral load count. Multiple blood samples were collected every 3 to 5 days to observe dynamic changes in blood chemistry. Infected hamsters showed consistent weight loss until day 7 pi At day 5 pi, histopathology of the lungs showed moderate to severe inflammation and the virus could be detected. These results indicate that SARS-CoV-2 has an acute onset and recovery course in the hamster infection model. During the acute onset, blood triglyceride levels increased significantly at day 3 pi During the recovery course, uric acid and low-density lipoprotein levels increased significantly, but the total protein and albumin levels decreased. Together, our study suggests that SARS-CoV-2 infection in hamsters not only causes lung damage but also causes long-term changes in blood biochemistry during the recovery process. IMPORTANCE COVID-19 is now considered a multiorgan disease with a wide range of manifestations. There are increasing reports of persistent and long-term effects after acute COVID-19, but the long-term health consequences of COVID-19 are not fully understood. This study reported for the first time the use of blood samples collected continuously in a SARS-CoV-2-infected hamster model, which provides more information about the dynamic changes in blood biochemistry during the acute and recovery phases of SARS-CoV-2 infection. Our study suggests that SARS-CoV-2 infection in hamsters not only causes lung damage but also causes long-term changes in blood biochemistry during the recovery process. The study may be used by several researchers and clinicians, especially those who are studying potential treatments for patients with post-acute COVID-19 syndrome.

Taxonomic Structure of Rhizosphere Bacterial Communities and Its Association With the Accumulation of Alkaloidal Metabolites in Sophora flavescens.

Plant secondary metabolites (SMs) play a crucial role in plant defense against pathogens and adaptation to environmental stresses, some of which are produced from medicinal plants and are the material basis of clinical efficacy and vital indicators for quality evaluation of corresponding medicinal materials. The influence of plant microbiota on plant nutrient uptake, production, and stress tolerance has been revealed, but the associations between plant microbiota and the accumulation of SMs in medicinal plants remain largely unknown. Plant SMs can vary among individuals, which could be partly ascribed to the shift in microbial community associated with the plant host. In the present study, we sampled fine roots and rhizosphere soils of Sophora flavescens grown in four well-separated cities/counties in China and determined the taxonomic composition of rhizosphere bacterial communities using Illumina 16S amplicon sequencing. In addition, the association of the rhizosphere bacterial microbiota with the accumulation of alkaloids in the roots of S. flavescens was analyzed. The results showed that S. flavescens hosted distinct bacterial communities in the rhizosphere across geographic locations and plant ages, also indicating that geographic location was a larger source of variation than plant age. Moreover, redundancy analysis revealed that spatial, climatic (mean annual temperature and precipitation), and edaphic factors (pH and available N and P) were the key drivers that shape the rhizosphere bacterial communities. Furthermore, the results of the Mantel test demonstrated that the rhizosphere bacterial microbiota was remarkably correlated with the contents of oxymatrine, sophoridine, and matrine + oxymatrine in roots. Specific taxa belonging to Actinobacteria and Chloroflexi were identified as potential beneficial bacteria associated with the total accumulation of matrine and oxymatrine by a random forest machine learning algorithm. Finally, the structural equation modeling indicated that the Actinobacteria phylum had a direct effect on the total accumulation of matrine and oxymatrine. The present study addresses the association between the rhizosphere bacterial communities and the accumulation of alkaloids in the medicinal plant S. flavescens. Our findings may provide a basis for the quality improvement and sustainable utilization of this medicinal plant thorough rhizosphere microbiota manipulation.

Unique Sulfur-Aromatic Interactions Contribute to the Binding of Potent Imidazothiazole Indoleamine 2,3-Dioxygenase Inhibitors.

Indoleamine 2,3-dioxygenase (IDO1) inhibitors are speculated to be useful in cancer immunotherapy, but a phase III clinical trial of the most advanced IDO1 inhibitor, epacadostat, did not meet its primary end point and was abandoned. In previous work, we identified the novel IDO1 inhibitor N-(4-chlorophenyl)-2-((5-phenylthiazolo[2,3-c][1,2,4]triazol-3-yl)thio)acetamide 1 through high-throughput screening (HTS). Herein, we report a structure-activity relationship (SAR) study of this compound, which resulted in the potent IDO1 inhibitor 1-(4-cyanophenyl)-3-(3-(cyclopropylethynyl)imidazo[2,1-b]thiazol-5-yl)thiourea 47 (hIDO IC50 = 16.4 nM). X-ray cocrystal structural analysis revealed that the basis for this high potency is a unique sulfur-aromatic interaction network formed by the thiourea moiety of 47 with F163 and F226. This finding is expected to inspire new approaches toward the discovery of potent IDO1 inhibitors in the future.

Discovery of Conformational Control Inhibitors Switching off the Activated c-KIT and Targeting a Broad Range of Clinically Relevant c-KIT Mutants.

Drug resistance due to acquired mutations that constitutively activate c-KIT is a significant challenge in the treatment of patients with gastrointestinal stromal tumors (GISTs). Herein, we identified 1-(5-ethyl-isoxazol-3-yl)-3-(4-{2-[6-(4-ethylpiperazin-1-yl)pyrimidin-4-ylamino]-thiazol-5-yl}phenyl)urea (10a) as a potent inhibitor against unactivated and activated c-KIT. The binding of 10a induced rearrangements of the DFG motif, αC-helix, juxtamembrane domain, and the activation loop to switch the activated c-KIT back to its structurally inactive state. To the best of our knowledge, it is the first structural evidence demonstrating how a compound can inhibit the activated c-KIT by switching back to its inactive state through a sequence of conformational changes. Moreover, 10a can effectively inhibit various c-KIT mutants and the proliferation of several GIST cell lines. The distinct binding features and superior inhibitory potency of 10a, together with its excellent efficacy in the xenograft model, establish 10a as worthy of further clinical evaluation in the advanced GISTs.

Tone-Replacement Error Diffusion for Multitoning.

Error diffusion is an efficient halftone method for mainly being applied on printers. The promising high image quality and processing efficiency endorse it as a popular and competitive candidate in halftoning and multitoning applications. The multitoning is an extension of halftoning, adopting more than two-tone levels for the improvement of the similarity between an original image and the converted image. Yet, the banding effect, indicating the areas with discontinuous tone level, disturbs the visual perception, and thus seriously degrades image quality. To solve the banding effect, the tone-replacement strategy is proposed in this paper. As documented in the experimental results, excellent tone-similarity as that of the original image and promising reconstructed dot-distribution can be provided simultaneously. Comparing with the former banding-free methods, the apparent improvements/features suggest that the proposed method can be a very competitive candidate for multitoning applications.

Efficient halftoning based on multiple look-up tables.

Look-up table (LUT) halftoning is an efficient way to construct halftone images and approximately simulate the dot distribution of the learned halftone image set. In this paper, a general mechanism named multiple look-up table (MLUT) halftoning is proposed to generate the halftones of direct binary search (DBS), whereas the high efficient characteristic of the LUT is still preserved. In the MLUT, the standard deviation is adopted as an important feature to classify various tables. In addition, the proposed quick standard deviation evaluation is employed to yield an extremely low computational complexity in calculating the standard deviation. In the parameter optimization, the autocorrelation is adopted because it can fully characterize the periodicity of dot distribution. Experimental results demonstrate that the dot distribution generated by the proposed method approximates to that of the DBS, which enables the proposed scheme as a very competitive candidate in the copying and printing industry.