A Cohort Study on Deficiency of ADA2 from China.

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

[Adionuclide therapy for metastatic castration-resistant prostate cancer: New advances].

Prostate cancer (PCa) is one of the most common tumors of the male urogenital system, ranking the second among male malignancies worldwide. Age is a major risk factor for PCa, and population aging leads to an increasing incidence of the malignancy. Androgen-deprivation therapy (ADT) is currently the first-line treatment of PCa, but with the advance of the tumor, many of the patients become resistant to ADT and develop castration-resistant prostate cancer (CRPC), which marks a transition of PCa to a hormone-refractory state associated with a poor prognosis. Metastatic CRPC (mCRPC) is the terminal stage of the disease and a leading cause of death. Despite many new advances in the treatment of mCRPC, its prognosis remains poor. For patients with mCRPC, classical treatment options with chemotherapy and androgen-blocking agents have limited survival benefit, and radionuclide therapy has become a novel therapeutic option for mCRPC. This paper focuses on the development of the radionuclide therapy for mCRPC in recent years.

[Low-intensity extracorporeal shock wave therapy for erectile dysfunction: An update].

Erectile dysfunction (ED) is the inability of men to consistently obtain and maintain sufficient penile erections to complete a satisfactory sex activity, significantly affecting men's quality of life. In recent years, a large number of studies have shown that low-intensity extracorporeal shock wave therapy (Li-ESWT) may improve erectile function by inducing angiogenesis and reversing the pathological process of the erectile tissue, and is a safe, effective and tolerable method for the treatment of vascular ED. This article reviews the pathophysiological mechanism and clinical application of Li-ESWT in the treatment of ED.

[Study on the efficacy and complications of patients undergoing radical surgery and radical radiotherapy for localized prostate cancer].

OBJECTIVE: To compare the efficacy and complications of radical surgery (RP) and radical radiotherapy (RRT). METHODS: The clinical data of patients diagnosed with localized prostate cancer in General Hospital of Eastern Theater Command with RP and RRT from January 2015 to December 2019, Observed and recorded patient preoperative and postoperative PSA levels, biochemical Relapse-free Survival and clinical Relapse-free Survival,and the occurrence of hematuria, urinary incontinence, erectile dysfunction, ankylurethria, diarrhea, hemoproctia and radiocystitis. RESULTS: A total of 150 patients with localized prostate cancer were included in this study, including 105 patients with RP and 45 patients undergoing RRT. There was no significant difference between the complication rates of hematuria, urinary incontinence, erectile dysfunction and ankylurethria(P>0.05).Patients in the RRT group had higher rates of diarrhea(20.00% vs 2.86%), hemoproctia(15.56% vs 1.90%) and radiocystitis(13.33% vs 0%) than those in the RP group, with significant differences (P<0.05). The 5-year bRFS was lower than that in the RP group (95.1% vs 90.7%), with no statistical significance (P=0.832); the 5-year cRFS in the RP group was lower than that in the RRT group (91.2% vs 89.6%), with no significant difference (P=0.971). CONCLUSION: The incidence of diarrhea, hemoproctia and radiocystitis was lower in the RP group than in the RRT group, and the recurrence-free survival was not significantly different between the two groups.

[Low-intensity extracorporeal shockwave therapy improves symptoms of erectile dysfunction: A preliminary study].

OBJECTIVE: To verify the effect and safety of low-intensity extracorporeal shockwave therapy (Li-ESWT) in improving the symptoms of ED, and provide some reference for further related large-scale clinical trials. METHODS: Twenty-six patients diagnosed with ED received Li-ESWT with an energy of 0.09 mJ/mm2 for 20 minutes once a week for 6 four-week courses. Before and at 3, 6, 9, and 12 months after treatment, we obtained the IIEF-5 and Erectile Hardness Scale (EHS) scores of the patients using questionnaires, recorded the incidence of treatment-related adverse reactions, compared the erectile function of the patients before and after treatment, and evaluated the effect and safety of Li-ESWT in improving ED-related symptoms. RESULTS: Compared with the baseline, the IIEF-5 scores of the patients were significantly increased (P < 0.01) while the EHS scores slightly increased at 3 months after Li-ESWT treatment (P > 0.05), both IIEF-5 and EHS scores were dramatically increased at 6 months (P < 0.01), and both significantly higher than at 3 months. At 9 months, EHS scores remained remarkably higher than the baseline (P < 0.01) although IIEF-5 scores slightly lower than at 6 months. At 12 months, however, IIEF-5 scores decreased, though still significantly higher than the baseline (P < 0.01), and EHS scores became lower than at 6 and 9 months (P < 0.05) but still markedly higher than before treatment (P < 0.05). Adverse reactions observed during the intervention mainly included pruritus (4.35%), pain (2.90%), paresthesia (2.17%), and petechiae/ecchymosis (2.90%). CONCLUSION: Li-ESWT can increase the IIEF-5 and EHS scores and improve the clinical symptoms of ED patients, with a low incidence of adverse reactions during the treatment.

[Influence factors of erectile dysfunction in patients with localized prostate cancer after radical surgery].

OBJECTIVE: To analyze the influential factors of erectile dysfunction (ED) in patients with localized prostate cancer (LPC) after radical surgery. METHODS: The clinical data of 150 male patients diagnosed with LPC and normal erectile function (EF) before surgery admitted to the Department of Urology of the Eastern Theatre General Hospital from January 2021 to January 2023 were retrospectively analyzed. The EF status of the patients 6 months after surgery was assessed using the International Erectile Function Index -5(IIEF-5). Age, Gleason score, PSA level, TNM stage, preoperative International prostatic symptom score (IPSS), preoperative prostate volume, smoking index, alcohol consumption index, educational level, comorbidities, operation mode, and psychosexual state were used as influencing factors to analyze their effects on postoperative ED. RESULTS: Of the 150 patients, 88 had ED and 62 had normal EF. Univariate analysis showed that age, preoperative IPSS, preoperative prostate volume, comorbidities and sexual and psychological status were significantly correlated with postoperative ED. Further multivariate logistic regression analysis showed that age, preoperative prostate volume, comorbidities and sexual and psychological status were independent factors influencing the occurrence of ED after RP in LPC patients. CONCLUSION: The recovery of sexual function of patients with localized prostate cancer after radical surgery is generally poor, and the incidence of ED is high. Its independent influencing factors include age, preoperative prostate volume, comorbidities and sexual psychological state, etc. Correct intervention of different influencing factors is required in clinical work. In order to provide a better diagnosis and treatment scheme for LPC patients undergoing radical treatment, reduce the incidence of postoperative ED and improve the quality of life of patients after surgery.

Genetically Encoded Phosphine Ligand for Metalloprotein Design.

Phosphine ligands are the most important class of ligands for cross-coupling reactions due to their unique electronic and steric properties. However, metalloproteins generally rely on nitrogen, sulfur, or oxygen ligands. Here, we report the genetic incorporation of P3BF, which contains a biocompatible borane-protected phosphine, into proteins. This step is followed by a straightforward one-pot strategy to perform deboronation and palladium coordination in aqueous and aerobic conditions. The genetically encoded phosphine ligand P3BF should significantly expand our ability to design functional metalloproteins.

Optofluidic tunable broadband distributed Bragg reflector based on liquid crystal polymer composites.

A dynamically reconfigurable liquid crystal (LC) photonic device is an important research field in modern LC photonics. We present a type of continuously tunable distributed Bragg reflector (DBR) based on LC polymer composites modulated via a novel optofluidic method. LC-templated DBR films are fabricated by photopolymerization under visible standing wave interference. The influences of the incident angle, incident light intensity, and content of ethanol as a pore-forming additive on the reflection behavior are discussed in detail. Then, the LC-templated DBR films are integrated into microfluidic channels and reversibly refilled by different organic solvents. The reconfigurable characteristics of optofluidic DBRs were demonstrated by changing the average refractive index (RI) of the mixed liquids and adjusting the flow rates, resulting in the dynamic and continuous variation of the reflection band within a specific visible light band. It is anticipated that the prototype optofluidic LC device will hopefully be applied to some specific scenarios where conventional means of regulation, such as electric, optical, and temperature fields, are unsuitable and possibly boost the development of microfluidic analysis techniques based on structural color.

An Analysis of Exhaust Emission of the Internal Combustion Engine Treated by the Non-Thermal Plasma.

Industries' air pollution causes serious challenges to modern society, among them exhaust gases from internal combustion engines, which are currently one of the main sources. This study proposes a non-thermal plasma (NTP) system for placement in the exhaust system of internal combustion engines to reduce the toxic contaminants (HC, CO, and NOx) of exhaust gases. This NTP system generates a high-voltage discharge that not only responds to the ion chemical reaction to eliminate NOx and CO, but that also generates a combustion reaction at the local high temperature of plasma to reduce HC. The NTP system was designed on both the front and rear of the exhaust pipe to analyze the difference of different exhaust flow rates under the specified frequency. The results indicate that the NTP system can greatly reduce toxic contaminants. The NTP reactor placed in the front of exhaust pipe gave HC and CO removal efficiency of about 34.5% and 16.0%, respectively, while the NTP reactor placed in the rear of exhaust pipe gave NOx removal efficiency of about 41.3%. In addition, the voltage and material directly affect the exhaust gases obviously. In conclusion, the proposed NTP system installed in the exhaust system can significantly reduce air pollutants. These results suggest that applying NTP to the combustion engine should be a useful tool to simultaneously reduce both emissions of NOx and CO.

Sub-200 fs soliton mode-locked fiber laser based on bismuthene saturable absorber.

Few-layer bismuthene is an emerging two-dimensional material in the fields of physics, chemistry, and material science. However, its nonlinear optical property and the related photonics device have been seldom studied so far. Here, we demonstrate a sub-200 fs soliton mode-locked erbium-doped fiber laser (EDFL) using a microfiber-based bismuthene saturable absorber for the first time, to the best of our knowledge. The bismuthene nanosheets are synthesized by the sonochemical exfoliation method and transferred onto the taper region of a microfiber by the optical deposition method. Stable soliton pulses centered at 1561 nm with the shortest pulse duration of about 193 fs were obtained. Our findings unambiguously imply that apart from its fantastic electric and thermal properties, few-layer bismuthene may also possess attractive optoelectronic properties for nonlinear photonics, such as mode-lockers, Q-switchers, optical modulators and so on.

Administration of USP7 inhibitor p22077 alleviates Angiotensin II (Ang II)-induced atrial fibrillation in Mice.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is an important contributor to mortality and morbidity. Ubquitin-specific protease 7 (USP7), one of the most abundant ubiquitin-specific proteases (USP), participated in many cellular events, such as cell proliferation, apoptosis, and tumourigenesis. However, its role in AF remains unknown. Here, the mice were treated with Ang II infusion to induce the AF model. Echocardiography was used to measure the atrial diameter. Electrical stimulation was programmed to measure the induction and duration of AF. The changes in atrial remodeling were measured using routine histologic analysis. Here, a significant increase in USP7 expression was observed in Ang II-stimulated atrial cardiomyocytes and atrial tissues, as well as in atrial tissues from patients with AF. The administration of p22077, the inhibitor of USP7, attenuated Ang II-induced inducibility and duration of AF, atrial dilatation, connexin dysfunction, atrial fibrosis, atrial inflammation, and atrial oxidase stress, and then inhibited the progression of AF. Mechanistically, the administration of p22077 alleviated Ang II-induced activation of TGF-ß/Smad2, NF-κB/NLRP3, NADPH oxidases (NOX2 and NOX4) signals, the up-regulation of CX43, ox-CaMKII, CaMKII, Kir2.1, and down-regulation of SERCA2a. Together, this study, for the first time, suggests that USP7 is a critical driver of AF and revealing USP7 may present a new target for atrial fibrillation therapeutic strategies.

Spatial and temporal variations of soil nutrients of cropland in Northeast China from the 1980s to the 2010s.

In recent years, the degradation of cropland soils in Northeast China, such as "thinned, barren, and hardened", has become increasingly serious, with consequences on sustainable development of agriculture. Based on the data from Soil Types of China (1980s) and Soil Series of China (2010s), we examined the change patterns of soil nutrient conditions across different regions and soil types in Northeast China over the past 30 years through the statistical analysis of large samples. The results showed that: 1) from the 1980s to the 2010s, soil nutrient indicators in Northeast China changed to different degrees. Soil pH decreased by 0.03. Soil organic matter (SOM) content decreasd most prominently, by 8.99 g·kg-1 or 23.6%. Soil total N (TN), total P (TP) and total K (TK) contents showed increasing trends, with increases of 17.1%, 46.8%, and 4.9%, respectively. 2) Changes in soil nutrient indicators differed across different provinces and cities. Soil acidification in Liaoning was the most obvious, with pH decreasing by 0.32. SOM content in Liaoning decreased most significantly, by 31.0%. Soil TN, TP, and TK contents in Liaoning increased most significantly by 73.8%, 248.1% and 44.0%, respectively. 3) The changes of soil nutrients varied greatly among soil types, with brown soil and kastanozems showing the greatest decrease in pH. The SOM content of all soil types showed a decreasing trend, with 35.4%, 33.8% and 26.0% reduction in brown soil, dark brown forest soil and chernozem respectively. The greatest increase in TN, TP and TK contents were observed in brown soil by 89.1%, 232.8%, and 48.5%, respectively. In summary, declining organic matter content and soil acidification were the core problems of soil degradation in Northeast China from the 1980s to the 2010s. Reasonable tillage methods and targeted conservation strategies are critically needed to ensure the sustai-nable development of agriculture in Northeast China.

Safety and long-term prognosis of simultaneous versus staged resection in synchronous colorectal cancer with liver metastasis: a systematic review and meta-analysis.

PURPOSE: The optimal time point for surgical resection of synchronous colorectal liver metastases (SCLMs) is still controversial. This meta-analysis evaluated the safety and long-term prognoses of simultaneous and staged resection of SCLM to provide a reference for clinical selection. METHODS: A systematic literature search for studies published by October 2022 was performed using PubMed, Web of Science, Embase, Scopus and Cochrane Library. The evaluated outcome parameters were total, gastrointestinal and hepatic complications, as well as perioperative mortality, intraoperative blood loss, total hospital stay, 5-year disease-free survival (DFS) and 5-year overall survival (OS). RESULTS: This meta-analysis included 22 nonrandomised and one randomised study comprising 4862 patients. The patients undergoing simultaneous resection of SCLM had similar total (OR = 0.88, 95% CI [0.66-1.19], P = 0.409), gastrointestinal (OR = 1.19, 95% CI [0.89-1.59], P = 0.241) and hepatic (OR = 1.04, 95% CI [0.83-1.31], P = 0.734) complications, as well as perioperative mortality (OR = 1.79, 95% CI [0.88-3.64], P = 0.108), 5-year DFS (HR = 1.26, 95% CI [0.96-1.66], P = 0.098) and 5-year OS (HR = 1.13, 95% CI [0.95-1.34], P = 0.164). Lower intraoperative blood loss (SMD = - 0.39, 95% CI [- 0.60 to - 0.18], P < 0.001) and shorter total hospital stay (WMD = - 5.43, 95% CI [- 7.29 to - 3.58], P < 0.001) were observed in the simultaneous-resection group versus the staged group. CONCLUSIONS: Simultaneous resection is safe and effective for SCLM patients. The long-term prognosis is equivalent to that of the traditional staged resection. Correct selection of resectable SCLM patients for the simultaneous resection of the primary tumour and liver metastases can be the first choice. Owing to the potential heterogeneity, more RCTs should be included to verify our conclusions.

Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice.

Hypertension is one of the common causes of pathological cardiac hypertrophy and a major risk for morbidity and mortality of cardiovascular diseases worldwide. Ubiquitin-Specific Protease 7 (USP7), the first identified deubiquitinating enzymes, participated in a variety of biological processes, such as cell proliferation, DNA damage response, tumourigenesis, and apoptosis. However, its role and mechanism in cardiac remodeling remain unclear. Here, our data indicated that USP7 expression was increased during Ang II-induced cardiac hypertrophy and remodeling in mice and humans with heart failure, while the administration of its inhibitor p22077 attenuated cardiac hypertrophy, cardiac fibrosis, inflammation, and oxidase stress. Mechanistically, the administration of p22077 inhibited the multiple signaling pathways, including AKT/ERK, TGF-ß/SMAD2/Collagen I/Collagen III, NF-κB/NLRP3, and NAPDH oxidases (NOX2 and NOX4). Taken together, these findings demonstrate that USP7 may be a new therapeutic target for hypertrophic remodeling and HF.

Cardiac-specific knockdown of Bhlhe40 attenuates angiotensin II (Ang II)-Induced atrial fibrillation in mice.

Atrial fibrosis and atrial inflammation are associated with the pathogenesis of atrial fibrillation (AF). Basic helix-loop-helix family member E40 (Bhlhe40) is an important transcription factor, which is involved in tumors, inflammation, apoptosis, viral infection, and hypoxia. However, its role and molecular mechanism in AF remain unclear. In this study, a mouse model of AF was induced by Ang II infusion. The atrial diameter was evaluated using echocardiography. Induction and duration of AF were measured by programmed electrical stimulation. Atrial structural remodeling was detected using routine histologic examinations. Our results showed that Bhlhe40 was significantly upregulated in angiotensin II (Ang II)-stimulated atrial cardiomyocytes and atrial tissues and in tissues from patients with AF. Cardiac-specific knockdown of Bhlhe40 in mice by a type 9 recombinant adeno-associated virus (rAAV9)-shBhlhe40 significantly ameliorated Ang II-induced atrial dilatation, atrial fibrosis, and atrial inflammation, as well as the inducibility and duration of AF. Mechanistically, cardiac-specific knockdown of Bhlhe40 attenuated Ang II-induced activation of NF-κB/NLRP3, TGF-1ß/Smad2 signals, the increased expression of CX43, and the decreased expression of Kv4.3 in the atria. This is the first study to suggest that Bhlhe40 is a novel regulator of AF progression, and identifying Bhlhe40 may be a new therapeutic target for hypertrophic remodeling and heart failure.

An Investigation on the Hardness of Polylactic Acid Parts Fabricated via Fused Deposition Modeling.

This paper investigated the hardness property of the fused deposition modeling (FDM)-printed PLA samples via different process parameters of printing and raster angles. The hardness data were sampled from the flat and edge surfaces of the samples. In addition, the effect of hardness characters after the ultraviolet (UV) curing process was analyzed. Furthermore, this research found that the printing and raster angles significantly affected the hardness value of the PLA part, which slightly increased after the UV irradiation. Moreover, the results of this study will provide a reference for the field of FDM application.

Sulfur-Doped Organosilica Nanodots as a Universal Sensor for Ultrafast Live/Dead Cell Discrimination.

Rapid and accurate differentiation between live and dead cells is highly desirable for the evaluation of cell viability. Here, we report the application of the orange-emitting sulfur-doped organosilica nanodots (S-OSiNDs) for ultrafast (30 s), ultrasensitive (1 µg/mL), and universal staining of the dead bacterial, fungal, and mammalian cells but not the live ones, which satisfies the requirements of a fluorescent probe that can specifically stain the dead cells. We further verify that the fluorescence distribution range of S-OSiNDs (which are distributed in cytoplasm and nucleus) is much larger than that of the commercial dead/fixed cell/tissue staining dye RedDot2 (which is distributed in the nucleus) in terms of dead mammalian cell staining, indicating that S-OSiNDs possess a better staining effect of dead cells than RedDot2. Overall, S-OSiNDs can be used as a robust fluorescent probe for ultrafast and accurate discrimination between dead and live cells at a single cell level, which may find a variety of applications in the biomedical field.

Case Report: A Novel Mutation in NFKB1 Associated With Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a rare, destructive inflammatory skin disease of which a painful nodule or pustule breaks down to form a progressively enlarging ulcer. Ulcerations associated with PG may occur after trauma or injury to the skin. The etiology has not been clearly elucidated. Our report described a PG patient with a heterozygous splice-donor-site mutation in NFKB1 (c.730+5G>A) causing the absence of exon 8 and the formation of truncated p105 (p.Asp191_Lys244delinsGlu; p105delEx8), which led to distinct symptoms of high fever and excessive inflammation in wound area after routine surgical procedures. The functional analysis showed that the variant caused reduced phosphorylation of p105 and resulted in the decreased processing of p105 to p50. We conclude that the patient's symptoms were caused by dysregulation of the NF-κB signaling pathway.

Effect of Printing Parameters on the Thermal and Mechanical Properties of 3D-Printed PLA and PETG, Using Fused Deposition Modeling.

Fused Deposition Modeling (FDM) can be used to manufacture any complex geometry and internal structures, and it has been widely applied in many industries, such as the biomedical, manufacturing, aerospace, automobile, industrial, and building industries. The purpose of this research is to characterize the polylactic acid (PLA) and polyethylene terephthalate glycol (PETG) materials of FDM under four loading conditions (tension, compression, bending, and thermal deformation), in order to obtain data regarding different printing temperatures and speeds. The results indicated that PLA and PETG materials exhibit an obvious tensile and compression asymmetry. It was observed that the mechanical properties (tension, compression, and bending) of PLA and PETG are increased at higher printing temperatures, and that the effect of speed on PLA and PETG shows different results. In addition, the mechanical properties of PLA are greater than those of PETG, but the thermal deformation is the opposite. The above results will be a great help for researchers who are working with polymers and FDM technology to achieve sustainability.

Effect of Printing Parameters on the Tensile Properties of 3D-Printed Polylactic Acid (PLA) Based on Fused Deposition Modeling.

In order to optimize the efficiency of the Fused deposition modeling (FDM) process, this study used polylactic acid (PLA) material under different parameters (the printing angle and the raster angle) to fabricate specimens and to explore its tensile properties. The effect of the ultraviolet (UV) curing process on PLA materials was also investigated. The results showed that the printing and raster angles have a high impact on the tensile properties of PLA materials. The UV curing process enhanced the brittleness and reduced the elongation of PLA material. Different effects were observed on tensile strength and modulus of specimens printed with different parameters after UV curing. The above results will be a great help for researchers who are working to achieve sustainability of PLA materials and FDM technology.