Enhanced native chemical ligation by peptide conjugation in trifluoroacetic acid.

Chemical ligation of peptides is increasingly used to generate proteins not readily accessible by recombinant approaches. However, a robust method to ligate "difficult" peptides remains to be developed. Here, we report an enhanced native chemical ligation strategy mediated by peptide conjugation in trifluoroacetic acid (TFA). The conjugation between a carboxyl-terminal peptide thiosalicylaldehyde thioester and a 1,3-dithiol-containing peptide in TFA proceeds rapidly to form a thioacetal-linked intermediate, which is readily converted into the desired native amide bond product through simple postligation treatment. The effectiveness and practicality of the method was demonstrated by the successful synthesis of several challenging proteins, including the SARS-CoV-2 transmembrane Envelope (E) protein and nanobodies. Because of the ability of TFA to dissolve virtually all peptides and prevent the formation of unreactive peptide structures, the method is expected to open new opportunities for synthesizing all families of proteins, particularly those with aggregable or colloidal peptide segments.

Identification of suitable habitats and priority conservation areas under climate change scenarios for the Chinese alligator (Alligator sinensis).

Amphibians and reptiles, especially the critically endangered Chinese alligators, are vulnerable to climate change. Historically, the decline in suitable habitats and fragmentation has restricted the distribution of Chinese alligators to a small area in southeast Anhui Province in China. However, the effects of climate change on range-restricted Chinese alligator habitats are largely unknown. We aimed to predict current and future (2050s and 2070s) Chinese alligator distribution and identify priority conservation areas under climate change. We employed species distribution models, barycenter migration analyses, and the Marxian model to assess current and future Chinese alligator distribution and identify priority conservation areas under climate change. The results showed that the lowest temperature and rainfall seasonality in the coldest month were the two most important factors affecting the distribution of Chinese alligators. Future predictions indicate a reduction (3.39%-98.41%) in suitable habitats and a westward shift in their distribution. Further, the study emphasizes that suitable habitats for Chinese alligators are threatened by climate change. Despite the impact of the Anhui Chinese Alligator National Nature Reserve, protection gaps persist, with 78.27% of the area lacking priority protected area. Our study provides crucial data for Chinese alligator adaptation to climate change and underscores the need for improved conservation strategies. Future research should refine conservation efforts, consider individual plasticity, and address identified limitations to enhance the resilience of Chinese alligator populations in the face of ongoing climate change.

An Enzyme-Cleavable Solubilizing-Tag Facilitates the Chemical Synthesis of Mirror-Image Proteins.

Mirror-image proteins (D-proteins) are useful in biomedical research for purposes such as mirror-image screening for D-peptide drug discovery, but the chemical synthesis of many D-proteins is often low yielding due to the poor solubility or aggregation of their constituent peptide segments. Here, we report a Lys-C protease-cleavable solubilizing tag and its use to synthesize difficult-to-obtain D-proteins. Our tag is easily installed onto multiple amino acids such as DLys, DSer, DThr, and/or the N-terminal amino acid of hydrophobic D-peptides, is impervious to various reaction conditions, such as peptide synthesis, ligation, desulfurization, and transition metal-mediated deprotection, and yet can be completely removed by Lys-C protease under denaturing conditions to give the desired D-protein. The efficacy and practicality of the new method were exemplified in the synthesis of two challenging D-proteins: D-enantiomers of programmed cell death protein 1 IgV domain and SARS-CoV-2 envelope protein, in high yield. This work demonstrates that the enzymatic cleavage of solubilizing tags under denaturing conditions is feasible, thus paving the way for the production of more D-proteins.

Global Scientific Trends in Continuous Renal Replacement Therapy from 2000 to 2023: A Bibliometric and Visual Analysis.

INTRODUCTION: Continuous renal replacement therapy (CRRT) is one of the most widely used blood purification and organ support methods in the ICU. However, the development process, the current status, hotspots, and future trends of CRRT remain unclear. METHOD: The WoSCC database was used to analyze CRRT research evolution and theme trends. VOSviewer was used to construct coauthorship, co-occurrence, co-citation, and network visualizations. CiteSpace is used to detect bursts for co-occurrence items. Several important subtopics were reviewed and discussed in more detail. RESULTS: Global publications increased from 56 in 2000 to 398 in 2023, a 710.71% increase. Blood Purification published the most manuscripts, followed by the International Journal of Artificial Organs. The USA, the San Bortolo Hospital, and Bellomo were the most productive and impactful institution, country, and author, respectively. Based on co-occurrence cluster analysis, five clusters emerged: (1) clinical applications and management of CRRT; (2) sepsis and CRRT; (3) CRRT anticoagulant management; (4) CRRT and antibiotic pharmacokinetics and pharmacodynamics; and (5) comparison of CRRT and intermittent hemodialysis. COVID-19, initiation, ECOMO, cefepime, guidelines, cardiogenic shock, biomarker, and outcome were the latest high-frequency keywords or strongest bursts, indicating the emerging frontiers of CRRT. CONCLUSIONS: There has been widespread publication and citation of CRRT research in the past 2 decades. We provide an overview of current trends, global collaboration patterns, basic knowledge, research hotspots, and emerging frontiers.

Role of Mn-LIPA in Sex Hormone Regulation and Gonadal Development in the Oriental River Prawn, Macrobrachium nipponense.

This study investigates the role of lysosomal acid lipase (LIPA) in sex hormone regulation and gonadal development in Macrobrachium nipponense. The full-length Mn-LIPA cDNA was cloned, and its expression patterns were analyzed using quantitative real-time PCR (qPCR) in various tissues and developmental stages. Higher expression levels were observed in the hepatopancreas, cerebral ganglion, and testes, indicating the potential involvement of Mn-LIPA in sex differentiation and gonadal development. In situ hybridization experiments revealed strong Mn-LIPA signaling in the spermatheca and hepatopancreas, suggesting their potential role in steroid synthesis (such as cholesterol, fatty acids, cholesteryl ester, and triglycerides) and sperm maturation. Increased expression levels of male-specific genes, such as insulin-like androgenic gland hormone (IAG), sperm gelatinase (SG), and mab-3-related transcription factor (Dmrt11E), were observed after dsMn-LIPA (double-stranded LIPA) injection, and significant inhibition of sperm development and maturation was observed histologically. Additionally, the relationship between Mn-LIPA and sex-related genes (IAG, SG, and Dmrt11E) and hormones (17ß-estradiol and 17α-methyltestosterone) was explored by administering sex hormones to male prawns, indicating that Mn-LIPA does not directly control the production of sex hormones but rather utilizes the property of hydrolyzing triglycerides and cholesterol to provide energy while influencing the synthesis and secretion of self-sex hormones. These findings provide valuable insights into the function of Mn-LIPA in M. nipponense and its potential implications for understanding sex differentiation and gonadal development in crustaceans. It provides an important theoretical basis for the realization of a monosex culture of M. nipponense.

A Binocular Stereo-Imaging-Perception System with a Wide Field-of-View and Infrared- and Visible Light-Dual-Band Fusion.

With the continuous evolution of autonomous driving and unmanned driving systems, traditional limitations such as a limited field-of-view, poor ranging accuracy, and real-time display are becoming inadequate to satisfy the requirements of binocular stereo-perception systems. Firstly, we designed a binocular stereo-imaging-perception system with a wide-field-of-view and infrared- and visible light-dual-band fusion. Secondly we proposed a binocular stereo-perception optical imaging system with a wide field-of-view of 120.3°, which solves the small field-of-view of current binocular stereo-perception systems. Thirdly, For image aberration caused by the wide-field-of-view system design, we propose an ellipsoidal-image-aberration algorithm with a low consumption of memory resources and no loss of field-of-view. This algorithm simultaneously solves visible light and infrared images with an aberration rate of 45% and 47%, respectively. Fourthly, a multi-scale infrared- and visible light-image-fusion algorithm is used, which improves the situational-awareness capabilities of a binocular stereo-sensing system in a scene and enhances image details to improve ranging accuracy. Furthermore, this paper is based on the Taylor model-calibration binocular stereo-sensing system of internal and external parameters for limit correction; the implemented algorithms are integrated into an NVIDIA Jetson TX2 + FPGA hardware framework, enabling near-distance ranging experiments. The fusion-ranging accuracy within 20 m achieved an error of 0.02 m, outperforming both visible light- and infrared-ranging methods. It generates the fusion-ranging-image output with a minimal delay of only 22.31 ms at a frame rate of 50 Hz.

Chemical synthesis of a 28 kDa full-length PET degrading enzyme ICCG by the removable backbone modification strategy.

Chemical protein synthesis offers a powerful way to access otherwise-difficult-to-obtain proteins such as mirror-image proteins. Although a large number of proteins have been chemically synthesized to date, the acquisition to proteins containing hydrophobic peptide fragments has proven challenging. Here, we describe an approach that combines the removable backbone modification strategy and the peptide hydrazide-based native chemical ligation for the chemical synthesis of a 28 kDa full-length PET degrading enzyme IGGC (a higher depolymerization efficiency of variant leaf-branch compost cutinase (LCC)) containing hydrophobic peptide segments. The synthetic ICCG exhibits the enzymatic activity and will be useful in establishing the corresponding mirror-image version of ICCG.

A Low-Delay Dynamic Range Compression and Contrast Enhancement Algorithm Based on an Uncooled Infrared Sensor with Local Optimal Contrast.

Real-time compression of images with a high dynamic range into those with a low dynamic range while preserving the maximum amount of detail is still a critical technology in infrared image processing. We propose a dynamic range compression and enhancement algorithm for infrared images with local optimal contrast (DRCE-LOC). The algorithm has four steps. The first involves blocking the original image to determine the optimal stretching coefficient by using the information of the local block. In the second, the algorithm combines the original image with a low-pass filter to create the background and detailed layers, compressing the background layer with a dynamic range of adaptive gain, and enhancing the detailed layer for the visual characteristics of the human eye. Third, the original image was used as input, the compressed background layer was used as a brightness-guided image, and the local optimal stretching coefficient was used for dynamic range compression. Fourth, an 8-bit image was created (from typical 14-bit input) by merging the enhanced details and the compressed background. Implemented on FPGA, it used 2.2554 Mb of Block RAM, five dividers, and a root calculator with a total image delay of 0.018 s. The study analyzed mainstream algorithms in various scenarios (rich scenes, small targets, and indoor scenes), confirming the proposed algorithm's superiority in real-time processing, resource utilization, preservation of the image's details, and visual effects.

Prevalence of developmental dysplasia of the hip (DDH) in infants: a systematic review and meta-analysis.

OBJECTIVE: To estimate the prevalence of developmental dysplasia of the hip (DDH) in infants with a systematic review and meta-analysis. METHOD: A literature search was conducted in April 2023, using databases such as Cochrane Library, PubMed, MEDLINE, CNKI, and SinoMed, without language restrictions. Eligible studies included cross-sectional studies reporting the prevalence of DDH among infants aged 0-12 months. Two independent reviewers manually selected and coded the studies, with any disagreements resolved by a third reviewer. Meta-analysis was performed using a random-effects model to calculate the prevalence of DDH. Regression analysis examined the trend of DDH prevalence, and stratification analysis explored heterogeneity between studies. RESULTS: A total of 65 studies involving 3 451 682 infants were included in the meta-analysis. None of the studies were classified as high quality, four were medium-to-high quality, 50 were low-to-medium quality, and eight were low quality. The pooled prevalence of DDH was 1.40% (95% CI: 0.86 to 2.28, I2=100%), and prevalence of dysplasia, subluxation, and dislocation was 1.45% (95% CI: 0.93 to 2.24, I2=97%), 0.37% (95% CI: 0.22 to 0.60, I2=94%), and 0.21% (95% CI: 0.13 to 0.34, I2=92%), respectively. Notably, the overall prevalence has a slight upward trend in the last three decades (ß=0.24, p=0.35), but the dysplasia was downward trend (ß=-0.48, p<0.01). Girls have higher risk of DDH than boys (1.46% vs 0.66%; Q=5.83, df=1, p=0.02). There were no significant differences based on gender, country, setting, or screening technique. CONCLUSION: The prevalence of DDH among infants is approximately one in a 100, with girls being at higher risk. Though the prevalence of dysplasia has decreased, there is a slight upward trend in overall DDH. Therefore, routine screening for DDH in infants is recommended to prevent more serious developmental problems.

[Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(â ¢): classification of granule dissolving behaviors].

Solubility is an important sensory quality attribute of traditional Chinese medicine(TCM) granules. In this paper, 90 batches of granules(30 batches of TCM formula granules, 30 batches of Chinese patent medicine granules and 30 batches of Japanese Kampo granules) were used as the research objects. The turbidity sensor was used to characterize the turbidity curve of the granule dissolution process. The classification system of granule dissolution behaviors was constructed from three dimensions: dissolution degree, equilibrium time, and dissolution mechanism. According to the equilibrium time, the granule dissolution rates were divided into three categories : faster(<100 s), general(101-300 s) and slow(>301 s). According to the turbidity curve profile, the granule dissolution mechanisms were classified into dissolution-controlled type(α-type), dispersion-controlled type(ß-type), and dispersion-controlled type followed by dissolution-controlled type(γ-type). The proportion of TCM formula granules, Chinese patent medicine granules and Japanese Kampo granules with complete dissolution or slight turbidity at the end of dissolution was 46.7%, 96.7%, and 10.0%. The proportion of TCM formula granules, Chinese patent medicine granules, and Japanese Kampo granules with faster dissolution rates(<100 s) was 23.3%, 26.7%, and 40.0%. The average dissolution rate of Japanese Kampo granules was faster than that of TCM formula granules, and it was slightly faster than the average dissolution rate of Chinese patent medicine granules. The dissolution mechanism of Chinese patent medicine granules was mainly α-type, while that of Japanese Kampo granules was mainly ß-type, and the three types of dissolution mechanisms of TCM formula granules accounted for a relatively average. The purpose of improving the solubility and dispersion of granules can be achieved by combining the comprehensive application of various functional excipients with the small dosage of Japanese Kampo granules and the wide addition scope of excipients. In the process of transforming TCM compound prescriptions into formulas, there is still much room for innovation in formula excipients and process optimization.

Insulin-like Androgenic Gland Hormone Induced Sex Reversal and Molecular Pathways in Macrobrachium nipponense: Insights into Reproduction, Growth, and Sex Differentiation.

This study investigated the potential to use double-stranded RNA insulin-like androgenic gland hormone (dsIAG) to induce sex reversal in Macrobrachium nipponense and identified the molecular mechanisms underlying crustacean reproduction and sex differentiation. The study aimed to determine whether dsIAG could induce sex reversal in PL30-male M. nipponense during a critical period. The sex-related genes were selected by performing the gonadal transcriptome analysis of normal male (dsM), normal female (dsFM), neo-female sex-reversed individuals (dsRM), and unreversed males (dsNRM). After six injections, the experiment finally resulted in a 20% production of dsRM. Histologically, dsRM ovaries developed slower than dsFM, but dsNRM spermathecae developed normally. A total of 1718, 1069, and 255 differentially expressed genes were identified through transcriptome sequencing of the gonads in three comparison groups, revealing crucial genes related to reproduction and sex differentiation, such as GnRHR, VGR, SG, and LWS. Principal Component Analysis (PCA) also distinguished dsM and dsRM very well. In addition, this study predicted that the eyestalks and the "phototransduction-fly" photoperiodic pathways of M. nipponense could play an important role in sex reversal. The enrichment of related pathways and growth traits in dsNRM were combined to establish that IAG played a significant role in reproduction, growth regulation, and metabolism. Finally, complete sex reversal may depend on specific stimuli at critical periods. Overall, this study provides valuable findings for the IAG regulation of sex differentiation, reproduction, and growth of M. nipponense in establishing a monoculture.

The effects of endogenous FSH and its receptor on oogenesis and folliculogenesis in female Alligator sinensis.

BACKGROUND: The precise mechanisms of hormone action responsible for the full course of events modulating folliculogenesis in crocodilian have not been determined, although histological features have been identified. RESULTS: The Alligator sinensis ovarian morphological characteristics observed at 1, 15, 30, 60, 90, and 300 days post hatching(dph) revealed that the dynamic changes in germ cells varied in different meiotic and developmental stages, confirming that the processes of folliculogenesis were protracted and asynchronous. The presence of endogenous follicle-stimulating hormone(FSH) mRNA and protein expression within the cerebrum at 1 dph, in parallel with the increase in germ cells within the germ cell nests(Nest) from 1 dph to 15 dph, suggested that endocrine regulation of the pituitary-gonad axis is an early event in oogonia division. Furthermore, the endogenous expression of FSH showed a trend of negative feedback augmentation accompanied by the exhaustion of maternal yolk E2 observed at 15 dph. Such significant elevation of endogenous FSH levels was observed to be related to pivotal events in the transition from mitosis to meiosis, as reflected by the proportion of oogonia during premeiosis interphase, with endogenous FSH levels reaching a peak at the earliest time step of 1 dph. In addition, the simultaneous upregulation of premeiotic marker STRA8 mRNA expression and the increase in endogenous FSH further verified the above speculation. The strongly FSHr-positive label in the oocytes within Pre-previtellogenic follicles was synchronized with the significant elevation of ovarian cAMP detected at 300 dph, which suggested that diplotene arrest maintenance during early vitellogenesis might be FSH dependent. In addition, preferential selection in asynchronous meiotic initiation has been supposed to act on somatic supportive cells and not directly on germ cells via regulation of FSH that in turn affects downstream estrogen levels. This suggestion was verified by the reciprocal stimulating effect of FSH and E2 on the accelerated meiotic marker SYCP3 and by the inhibited cell apoptosis demonstrated in ovarian cell culture in vitro. CONCLUSION: The corresponding results contribute an expansion of the understanding of physiological processes and shed some light on the specific factors responsible for gonadotropin function in the early folliculogenesis of crocodilians.

G-protein couple receptor (GPER1) plays an important role during ovarian folliculogenesis and early development of the Chinese Alligator.

The critical role of the G protein-coupled receptor 1 (GPER1), a member of the seven-transmembrane G protein-coupled receptor family, in the functional regulation of oocytes accumulated abundant theories in the early research on model animals. However, the full-length cDNA encoding GPER1 and its role in the folliculogenesis has not been illustrated in crocodilians. 0.5, 3, and 12 months old Alligator sinensis cDNA samples were used to clone the full-length cDNA encoding GPER1. Immunolocalization and quantitative analysis were performed using Immunofluorescence technique, RT-PCR and Western blot. Simultaneously, studies on GPER1's promoter deletion and cis-acting transcriptional regulation mechanism were conducted. Immunolocalization staining for the germline marker DDX4 and GPER1 demonstrated that DDX4-positive oocytes were clustered tightly together within the nests, whereas scarcely any detectable GPER1 was present in the oocytes nest in Stage I. After that, occasionally GPER1-positive immunosignal was observed in oocytes and somatic cells additional with the primordial follicles, and it was mainly located at the granulosa cells or thecal cells within the early PFs in the Stage III. The single mutation of the putative SP1 motif, double mutating of Ets/SP1 and SP1/CRE binding sites all depressed promoter activities. This result will help to investigate the role of GPER1 in the early folliculogenesis of A. sinensis.

Effects of altered excitation-inhibition imbalance by repetitive transcranial magnetic stimulation for self-limited epilepsy with centrotemporal spikes.

Objectives: Patients with self-limited epilepsy with centrotemporal spikes (SeLECTS) with electrical status epilepticus in sleep (ESES) have generalized cognitive impairment, yet treatment options are limited. Our study aimed to examine the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on SeLECTS with ESES. In addition, we applied electroencephalography (EEG) aperiodic components (offset and slope) to investigate the improvement of rTMS on the excitation-inhibition imbalance (E-I imbalance) in the brain of this group of children. Methods: Eight SeLECTS patients with ESES were included in this study. Low-frequency rTMS (≤1 Hz) was applied for 10 weekdays in each patient. To assess the clinical efficacy and changes in E-I imbalance, EEG recordings were performed both before and after rTMS. Seizure-reduction rate and spike-wave index (SWI) were measured to investigate the clinical effects of rTMS. The aperiodic offset and slope were calculated to explore the effect of rTMS on E-I imbalance. Results: Five of the eight patients (62.5%) were seizure-free within 3 months after stimulation, with treatment effects decreasing with longer follow-ups. The SWI decreased significantly at 3 and 6 months after rTMS compared with the baseline (P = 0.0157 and P = 0.0060, respectively). The offset and slope were compared before rTMS and within 3 months after stimulation. The results showed a significant reduction in the offset after stimulation (P < 0.0001). There was a remarkable increase in slope after the stimulation (P < 0.0001). Conclusion: Patients achieved favorable outcomes in the first 3 months after rTMS. The ameliorative effect of rTMS on SWI may last up to 6 months. Low-frequency rTMS could reduce firing rates in neuronal populations throughout the brain, which was most pronounced at the site of stimulation. A significant reduction in the slope after rTMS treatment suggested an improvement in the E-I imbalance in the SeLECTS.

Backbone-Installed Split Intein-Assisted Ligation for the Chemical Synthesis of Mirror-Image Proteins.

Membrane-associated D-proteins are an important class of synthetic molecules needed for D-peptide drug discovery, but their chemical synthesis using canonical ligation methods such as native chemical ligation is often hampered by the poor solubility of their constituent peptide segments. Here, we describe a Backbone-Installed Split Intein-Assisted Ligation (BISIAL) method for the synthesis of these proteins, wherein the native L-forms of the N- and C-intein fragments of the unique consensus-fast (Cfa) (i.e. L-CfaN and L-CfaC ) are separately installed onto the two D-peptide segments to be ligated via a removable backbone modification. The ligation proceeds smoothly at micromolar (µM) concentrations under strongly chaotropic conditions (8.0 M urea), and the subsequent removal of the backbone modification groups affords the desired D-proteins without leaving any "ligation scar" on the products. The effectiveness and practicality of the BISIAL method are exemplified by the synthesis of the D-enantiomers of the extracellular domains of T cell immunoglobulin and ITIM domain (TIGIT) and tropomyosin receptor kinase C (TrkC). The BISIAL method further expands the chemical protein synthesis ligation toolkit and provides practical access to challenging D-protein targets.

An improved 3D KiU-Net for segmentation of liver tumor.

It is a challenging task to accurately segment liver tumors from Computed Tomography (CT) images. The widely used U-Net and its variants generally suffer from the issue to accurately segment the detailed edges of small tumors, because the progressive down sampling operations in the encoder module will gradually increase the receptive fields. These enlarged receptive filed have limited ability to learn the information about tiny structures. KiU-Net is a newly proposed dual-branch model that can effectively perform image segmentation for small targets. However, the 3D version of KiU-Net has high computational complexity, which limits its application. In this work, an improved 3D KiU-Net (named TKiU-NeXt) is proposed for liver tumor segmentation from CT images. In TKiU-NeXt, a Transformer-based Kite-Net (TK-Net) branch is proposed to build the over-complete architecture to learn more detailed features for small structures, and an extended 3D version of UNeXt is developed to replace the original U-Net branch, which can effectively reduce computational complexity but still with superior segmentation performance. Moreover, a Mutual Guided Fusion Block (MGFB) is designed to effectively learn more features from two branches and then fuse the complementary features for image segmentation. The experimental results on two public CT datasets and a private dataset demonstrate that the proposed TKiU-NeXt outperforms all the compared algorithms, and it also has less computational complexity. It suggests the effectiveness and efficiency of TKiU-NeXt.

Effects of Eggshell Thickness, Calcium Content, and Number of Pores in Erosion Craters on Hatching Rate of Chinese Alligator Eggs.

The Chinese alligator (Alligator sinensis), found only in a small region in southeastern Anhui Province, is listed as critically endangered (CR) by the International Union for Conservation of Nature (IUCN) due to its current declining population trend. Any abnormalities in the physical properties of an egg can decrease the hatching rate. In particular, eggshells play an essential role in embryo development, motivating us to analyze the microstructures of the eggshells of Chinese alligators. In this study, we categorized the eggshells into two groups, based on the hatching rates, and analyzed the relationship between the eggshell parameters (eggshell thickness, calcium content, and number of pores in erosion craters) and the hatching rate, as well as the relationships between the eggshell parameters. We found that the shells of the eggs with high hatching rates were thicker than those of the eggs with low hatching rates. There were also fewer erosion-crater pores on the surfaces of the eggs with high hatching rates than on the surfaces of the eggs with low hatching rates. Moreover, the shell Ca content was significantly higher in the eggs with high hatching rates than in the eggs with low hatching rates. Cluster modeling indicated that the highest hatching rate occurred when the eggshell thickness was 200-380 µm and there were 1-12 pores. These results suggest that eggs with adequate Ca contents, thicker shells, and less air permeability are more likely to hatch. Furthermore, our findings can inform future studies, which will be vital for the survival of the critically endangered Chinese alligator species.

Improving CBCT image quality to the CT level using RegGAN in esophageal cancer adaptive radiotherapy.

OBJECTIVE: This study aimed to improve the image quality and CT Hounsfield unit accuracy of daily cone-beam computed tomography (CBCT) using registration generative adversarial networks (RegGAN) and apply synthetic CT (sCT) images to dose calculations in radiotherapy. METHODS: The CBCT/planning CT images of 150 esophageal cancer patients undergoing radiotherapy were used for training (120 patients) and testing (30 patients). An unsupervised deep-learning method, the 2.5D RegGAN model with an adaptively trained registration network, was proposed, through which sCT images were generated. The quality of deep-learning-generated sCT images was quantitatively compared to the reference deformed CT (dCT) image using mean absolute error (MAE), root mean square error (RMSE) of Hounsfield units (HU), and peak signal-to-noise ratio (PSNR). The dose calculation accuracy was further evaluated for esophageal cancer radiotherapy plans, and the same plans were calculated on dCT, CBCT, and sCT images. RESULTS: The quality of sCT images produced by RegGAN was significantly improved compared to the original CBCT images. ReGAN achieved image quality in the testing patients with MAE sCT vs. CBCT: 43.7 ± 4.8 vs. 80.1 ± 9.1; RMSE sCT vs. CBCT: 67.2 ± 12.4 vs. 124.2 ± 21.8; and PSNR sCT vs. CBCT: 27.9 ± 5.6 vs. 21.3 ± 4.2. The sCT images generated by the RegGAN model showed superior accuracy on dose calculation, with higher gamma passing rates (93.3 ± 4.4, 90.4 ± 5.2, and 84.3 ± 6.6) compared to original CBCT images (89.6 ± 5.7, 85.7 ± 6.9, and 72.5 ± 12.5) under the criteria of 3 mm/3%, 2 mm/2%, and 1 mm/1%, respectively. CONCLUSION: The proposed deep-learning RegGAN model seems promising for generation of high-quality sCT images from stand-alone thoracic CBCT images in an efficient way and thus has the potential to support CBCT-based esophageal cancer adaptive radiotherapy.

Long-term clinical outcomes and prognosis after definitive radiotherapy for patients with cervical esophageal squamous cell carcinoma: a single-institution retrospective study.

Background: Definitive radiotherapy has become a more common treatment for cervical esophageal squamous cell carcinoma (CESCC), but data about long-term clinical outcomes is still relatively sparse. The purpose of this study was to describe long-term clinical outcomes after definitive radiotherapy for CESCC, and identify the prognostic factors influencing these outcomes. Methods: We retrospectively analyzed all patients who received definitive radiotherapy for CESCC at our institution between 2006 and 2014. The overall survival (OS) rate, locoregional failure-free survival (LRFFS) rate, and toxicities were retrospectively evaluated during long-term follow-up. Univariate and multivariate analyses were performed to identify prognostic factors. Results: A total of 120 patients were included for analysis. The median prescribed radiation dose for the gross tumor and metastatic lymph nodes was 60 Gy. Elective nodal irradiation (ENI) was performed on 99 patients (83%); 90 patients (75%) received concurrent chemotherapy. The OS rates were 22.7% at 5 years and 14.9% at 8 years. The LRFFS rates at 3, 5, and 8 years were 27.5%, 21.7%, and 15.0%, respectively. The univariate analysis suggested that N classification and non-regional lymph node metastasis (M1Lym) status were independent risk factors for overall survival (P<0.01). A dose of more than 60 Gy didn't have a statistically significant influence in the multivariate analysis, although a total dose of more than 60 Gy was associated with improved survival in the univariate analysis. Concurrent chemotherapy was not associated with OS or LRFFS time in the univariate or multivariate analysis. A total of 74 patients (61.7%) experienced locoregional treatment failure. The most commonly documented acute toxicities were grade 1 and grade 2 toxicities in 61 patients (50.8%). There were 2 patients diagnosed with hypothyroidism as a late toxicity event. Conclusions: Definitive radiotherapy is a reasonable curative treatment option with laryngopharyngeal preservation for CESCC patients. Radical treatments for lymph node metastases may improve the OS and LRFFS times. Monitoring for thyroid function may be warranted during long-term follow-up.

Real-world outcomes of anti-vascular endothelial growth factor therapy for retinal vascular vein occlusion in Tibet, China.

AIM: To evaluate the outcomes of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for patients with retinal vein occlusion (RVO) related-macular edema (ME) in Tibetan. METHODS: A retrospective, observational, single-center study. The demographic and clinical data of 90 RVO Tibetan patients (93 eyes) treated with either ranibizumab or conbercept in Tibet Autonomous Region People's Hospital from Jan 2018 to December 2019 were collected. RESULTS: The mean patient age was 56.8±10.6y, 45 (50%) of them were female. The mean living altitude was 3867.8±567.9 m. At the last visit, the best-corrected visual acuity (BCVA) significantly increased (52.2±21.8 letters) in comparison with the baseline (38.2±24.1 letters, P<0.001); while the central retinal thickness (CRT) significantly reduced (245.5±147.6 µm) in comparison with the baseline (504.1±165.2 µm, P<0.001). The 43.0% of the eyes gained ≥15 letters, 60.2% of the eyes gained ≥10 letters, and 78.5% of the eyes gained ≥5 letters. No vision loss was noted in 92.5% of the eyes, 4 eyes lost more than 10 letters during follow-up period. The mean number of injections was 2.4±1.8. No severe ocular or systemic adverse events related to either the drug or injection were noted. CONCLUSION: Anti-VEGF therapy is effective and safe in Tibetan patients for the treatment of RVO related ME.