ß-glucan combined with Envafolimab and Endostar as immune rechallenge for metastatic non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitor rechallenge has emerged as a prominent study area in non-small cell lung cancer (NSCLC). ß-glucan was reported to reverse resistance to anti-PD-1/PD-L1 inhibitors by regulating the tumor microenvironment. In this self-initiated clinical trial (ChiCTR2100054796), NSCLC participants who have previously failed anti-PD-1 therapy received ß-glucan (500 mg, bid, d1-21), Envafolimab (300 mg, d1) and Endostar (210 mg, civ72h) every 3 weeks until disease progression or unacceptable toxicity. The clinical efficacy and adverse events were observed, while serum samples were collected for proteomic analysis. RESULTS: Twenty Three patients were enrolled from January 2022 to March 2023 (median age, 65 years; male, n = 18 [78.3%]; squamous NSCLC, n = 9 [39.1%]; mutant type, n = 13 [56.5%]). The overall response rate (ORR) was 21.7% and disease control rate (DCR) was 73.9%. Median progression-free survival (mPFS) and median overall survival (mOS) was 4.3 months [95% CI: 2.0-6.6] and 9.8 months [95% CI: 7.2-12.4], respectively. The mPFS between PD-L1 positive and negative subgroup has significant difference (6.3 months vs. 2.3 months, p = 0.002). Treatment-related adverse events (TRAEs) occurred in 52.2% of patients. The most common TRAEs were hypothyroidism (26.1%) and fatigue (26.1%). 2 (8.7%) grade 3 adverse events were reported. No adverse reaction related deaths have been observed. Proteomic analysis revealed that the levels of CASP-8, ARG1, MMP12, CD28 and CXCL5 correlated with resistance to the treatment while the levels of CD40-L and EGF related to the favorable response. CONCLUSION: ß-glucan combined with Envafolimab and Endostar has considerable efficacy and safety for immune rechallenge in metastatic NSCLC patients who failed of anti-PD-1 treatment previously, especially for PD-L1 positive patients.

Comparative Study Between Variable Flip Angle and Modified Look-Locker Inversion Recovery for Evaluating Renal Interstitial Fibrosis.

BACKGROUND: Variable flip angle (VFA) and modified Look-Locker inversion recovery (MOLLI) are frequently used for noninvasive evaluation of renal interstitial fibrosis (IF) in chronic kidney disease (CKD). However, controversy remains over which method is preferred. PURPOSE: To compare the diagnostic efficacy of VFA and MOLLI for T1 mapping in evaluating renal IF. STUDY TYPE: Prospective. SUBJECTS: Fifty-one participants with CKD (CKD stage 1-5, 35 males) and 18 healthy volunteers (eight males). FIELD STRENGTH/SEQUENCE: 3.0 T, three-dimensional gradient echo sequence for B1+ VFA, and two-dimensional gradient echo sequence for MOLLI. ASSESSMENT: Image quality was assessed on a five-point scale. Cortex and medulla T1 values (cT1 and mT1), corticomedullary T1 value difference (ΔT1, medulla - cortex), and corticomedullary T1 value ratio (ratio T1, cortex:medulla) were compared between VFA and MOLLI as well as between IF grade (0-4) based on biopsy. STATISTICAL TESTS: Intraclass correlation coefficient, Bland-Altman analysis, analysis of variance, Kruskal-Wallis test, correlation analysis, and receiver operating characteristics analysis with the area under the curve (AUC). P-value <0.05 was considered significant. RESULTS: MOLLI provided significantly better image quality compared to VFA. cT1 and mT1 values significantly differed between VFA and MOLLI (cT1-VFA: 1771.4 ± 139.4 msec vs. cT1-MOLLI: 1729.9 ± 132.1 msec; mT1-VFA: 2076.0 [interquartile range (IQR): 2045.9-2129.9] msec vs. mT1-MOLLI: 2039.2 [IQR: 1997.8-2071.6] msec). ΔT1 and ratio T1 values were not different between VFA and MOLLI (ΔT1: 300.8 ± 71.4 vs. 306.0 ± 78.4, respectively, P = 0.33 and ratio T1: 0.85 ± 0.038 vs. 0.85 ± 0.041, respectively, P = 0.064). No difference was observed between T1 variables and T1 mapping methods in diagnosing IF. DATA CONCLUSION: ΔT1 and ratio T1 were not different between VFA and MOLLI. Both VFA and MOLLI are effective for noninvasive assessment of renal IF. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

A retrospective analysis of comorbidities in patients with psoriasis at a single centre.

Introduction: Psoriasis is a chronic inflammatory disease occurring worldwide. It is currently considered a multi-system disease, which is associated with several comorbidities. Aim: To deeply understand the clinical characteristics of psoriasis comorbidities and explore the relationship between psoriasis comorbidities, different subtypes and related influencing factors. Material and methods: This retrospective study analysed data from the electronic inpatient medical record system of dermatology and non-dermatology departments at a tertiary hospital in China. We collected relevant demographic data and clinical features of all patients diagnosed with psoriasis from January 2013 to September 2023. Results: This study ultimately included a total of 1097 patients with psoriasis. Psoriasis vulgaris was the most common among the subtypes of psoriasis, with 957 (87.2%) cases. The sample consisted of 65.6% of males and 34.4% of females, with an average age of 53.5 ±15.2 years. Common comorbidities of psoriasis included hypertension (38.2%), hyperlipidaemia (29.4%), type 2 diabetes mellitus (24.6%), fatty liver disease (21.4%), coronary heart disease (21.0%), tumours (15.5%), gastroduodenal disease (14.4%), osteoarthropathy (11.8%), and cerebrovascular disease (10.8%). The incidence of hypertension (p = 0.015), hyperuricemia (p < 0.001), osteoarthropathy (p < 0.001), and autoimmune disease (p = 0.003) among different subtypes of psoriasis showed statistically significant differences. In addition, gender, smoking and alcohol consumption all have significant impacts on the distribution of comorbidities. Conclusions: The distribution of psoriasis comorbidities and complications varies among different subtypes of psoriasis. Lifestyles such as smoking and alcohol abuse, as well as gender, are also associated with the occurrence of psoriasis comorbidities.

Correlation between chemical denaturation and the unfolding energetics of Acanthamoeba actophorin.

The actin filament network is in part remodeled by the action of a family of filament severing proteins that are responsible for modulating the ratio between monomeric and filamentous actin. Recent work on the protein actophorin from the amoeba Acanthamoeba castellani identified a series of site-directed mutations that increase the thermal stability of the protein by 22°C. Here, we expand this observation by showing that the mutant protein is also significantly stable to both equilibrium and kinetic chemical denaturation, and employ computer simulations to account for the increase in thermal or chemical stability through an accounting of atomic-level interactions. Specifically, the potential of mean force (PMF) can be obtained from steered molecular dynamics (SMD) simulations in which a protein is unfolded. However, SMD can be inefficient for large proteins as they require large solvent boxes, and computationally expensive as they require increasingly many SMD trajectories to converge the PMF. Adaptive steered molecular dynamics (ASMD) overcomes the second of these limitations by steering the particle in stages, which allows for convergence of the PMF using fewer trajectories compared with SMD. Use of the telescoping water scheme within ASMD partially overcomes the first of these limitations by reducing the number of waters at each stage to only those needed to solvate the structure within a given stage. In the PMFs obtained from ASMD, the work of unfolding Acto-2 was found to be higher than the Acto-WT by approximately 120 kCal/mol and reflects the increased stability seen in the chemical denaturation experiments. The evolution of the average number of hydrogen bonds and number of salt bridges during the pulling process provides a mechanistic view of the structural changes of the actophorin protein as it is unfolded, and how it is affected by the mutation in concert with the energetics reported through the PMF.

The ribosomal protein P0A is required for embryo development in rice.

BACKGROUND: The P-stalk is a conserved and vital structural element of ribosome. The eukaryotic P-stalk exists as a P0-(P1-P2)2 pentameric complex, in which P0 function as a base structure for incorporating the stalk onto 60S pre-ribosome. Prior studies have suggested that P0 genes are indispensable for survival in yeast and animals. However, the functions of P0 genes in plants remain elusive. RESULTS: In the present study, we show that rice has three P0 genes predicted to encode highly conserved proteins OsP0A, OsP0B and OsP0C. All of these P0 proteins were localized both in cytoplasm and nucleus, and all interacted with OsP1. Intriguingly, the transcripts of OsP0A presented more than 90% of the total P0 transcripts. Moreover, knockout of OsP0A led to embryo lethality, while single or double knockout of OsP0B and OsP0C did not show any visible defects in rice. The genomic DNA of OsP0A could well complement the lethal phenotypes of osp0a mutant. Finally, sequence and syntenic analyses revealed that OsP0C evolved from OsP0A, and that duplication of genomic fragment harboring OsP0C further gave birth to OsP0B, and both of these duplication events might happen prior to the differentiation of indica and japonica subspecies in rice ancestor. CONCLUSION: These data suggested that OsP0A functions as the predominant P0 gene, playing an essential role in embryo development in rice. Our findings highlighted the importance of P0 genes in plant development.

Value of multiparametric magnetic resonance imaging for evaluating chronic kidney disease and renal fibrosis.

OBJECTIVES: To identify optimized MRI markers for evaluating chronic kidney disease (CKD) and renal interstitial fibrosis (IF). MATERIALS AND METHODS: This prospective study included 43 patients with CKD and 20 controls. The CKD group was divided into mild and moderate-to-severe subgroups based on pathological results. Scanned sequences included T1 mapping, R2* mapping, intravoxel incoherent motion imaging, and diffusion-weighted imaging. One-way analyses of variance were used to compare MRI parameters among groups. Correlations of MRI parameters with estimated glomerular filtration rate (eGFR) and renal IF were analyzed using age as covariates. The support vector machine (SVM) model was used to evaluate the diagnostic efficacy of multiparametric MRI. RESULTS: Compared to control values, renal cortical apparent diffusion coefficient (cADC), medullary ADC (mADC), cortical pure diffusion coefficient (cDt), medullary Dt (mDt), cortical shifted apparent diffusion coefficient (csADC), and medullary sADC (msADC) values gradually decreased in the mild and moderate-to-severe groups, while cortical T1 (cT1) and medullary T1 (mT1) values gradually increased. Values of cADC, mADC, cDt, mDt, cT1, mT1, csADC, and msADC were significantly associated with eGFR and IF (p < 0.001). The SVM model indicated that multiparametric MRI combining cT1 and csADC can distinguish patients with CKD from controls with high accuracy (0.84), sensitivity (0.70), and specificity (0.92) (AUC: 0.96). Multiparametric MRI combining cT1 and cADC exhibited high accuracy (0.91), sensitivity (0.95), and specificity (0.81) for evaluating IF severity (AUC: 0.96). CONCLUSION: Multiparametric MRI combining T1 mapping and diffusion imaging may be of clinical utility in non-invasive assessment of CKD and IF. CLINICAL RELEVANCE STATEMENT: This study shows that multiparametric MRI combining T1 mapping and diffusion imaging may be clinically useful in the non-invasive assessment of chronic kidney disease (CKD) and interstitial fibrosis; this could provide information for risk stratification, diagnosis, treatment, and prognosis. KEY POINTS: • Optimized MRI markers for evaluating chronic kidney disease and renal interstitial fibrosis were investigated. • Renal cortex/medullary T1 values increased as interstitial fibrosis increased; cortical shifted apparent diffusion coefficient (csADC) correlated significantly with eGFR and interstitial fibrosis. • Support vector machine (SVM) combining cortical T1 (cT1) and csADC/cADC effectively identifies chronic kidney disease and accurately predicts renal interstitial fibrosis.

Purinergic signaling in myocardial ischemia-reperfusion injury.

Purines and their derivatives, extensively distributed in the body, act as a class of extracellular signaling molecules via a rich array of receptors, also known as purinoceptors (P1, P2X, and P2Y). They mediate multiple intracellular signal transduction pathways and participate in various physiological and pathological cell behaviors. Since the function in myocardial ischemia-reperfusion injury (MIRI), this review summarized the involvement of purinergic signal transduction in diversified pathological processes, including energy metabolism disorder, oxidative stress injury, calcium overload, inflammatory immune response, platelet aggregation, coronary vascular dysfunction, and cell necrosis and apoptosis. Moreover, increasing evidence suggests that purinergic signaling also mediates the prevention and treatment of MIRI, such as ischemic conditioning, pharmacological intervention, and some other therapies. In conclusion, this review exhibited that purinergic signaling mediates the complex processes of MIRI which shows its promising application and prospecting in the future.

Structurally Diverse Sesquiterpenoids from the Genus of Ainsliaea.

The genus of Ainsliaea embraces approximately 70 recognized species, many of which have been used to treat various diseases in folklore medicines. As the main metabolites of Ainsliaea plants, Ainsliaea sesquiterpenoids have drawn considerable attention in related scientific communities due to their intriguing structures and a variety of bioactivities. In this review, we intend to provide a full-aspect coverage of sesquiterpenoids reported from the genus of Ainsliaea, including 145 monomeric sesquiterpenoids and 30 oligomeric ones. Multiple aspects will be summarized, including their classification, distributions, structures, bioactivities, and biomimetic syntheses. In addition, their possible biosynthetic pathway will be discussed in detail.

Effect of bovine lactoferricin on the growth performance, digestive capacity, immune responses and disease resistance in Pacific white shrimp, Penaeus vannamei.

The present study evaluated the growth performance, digestive enzyme activity, non-specific immunity, immunity and growth genes in Penaeus vannamei fed diets supplemented with Bovine lactoferricin (the basal diet without Bovine lactoferricin, the control; 1.0‰ Bovine lactoferricin，LCB1; 1.5‰ Bovine lactoferricin，LCB1.5; 2.0‰ Bovine lactoferricin, LCB2; 2.5‰ Bovine lactoferricin, LCB2.5) for 56 days. The feeding trial showed that the final weight, weight gain rate, and specific growth rate of the shrimp were improved significantly, while the feed conversion ratio was reduced significantly in the LCB1.5 group compared to the control (P < 0.05). The challenge test of Vibrio parahaemolyticus showed that the cumulative mortalities of shrimp in the LCB1.5, LCB2 and LCB2.5 groups were significantly lower than that in the control (P < 0.05). Compared with the control, Lipase and Trypsin activities in the hepatopancreas of LCB1.5 and LCB2 groups were significantly enhanced (P < 0.05). Compared with the control, alkaline phosphatase, acid phosphatase activities in the hepatopancreas and the relative expression levels of Relish, Toll, JAK, STAT, TOR, Raptor, 4E-BP, eIF4E1α, eIF4E2 genes in the hepatopancreas of LCB1.5, LCB2 and LCB2.5 groups were all significantly enhanced (P < 0.05). These results suggested that dietary Bovine lactoferricin could improve the growth performance, digestive capacity and immune responses of shrimp. When resistance against Vibrio parahaemolyticus in shrimp is considered, high dosage of Bovine lactoferricin showed a better effect than low dosage of Bovine lactoferricin. However, high dosage of Bovine lactoferricin can have a negative impact on the growth performance of shrimp. Considering collectively the above, Bovine lactoferricin could improve the growth performance, digestive enzymes activities, immune responses and disease resistance of P. vannamei.

Bovine lactoferricin on non-specific immunity of giant freshwater prawns, Macrobrachium rosenbergii.

This study aimed to investigate the effects of dietary Bovine lactoferricin (LFcinB) on the growth performance and non-specific immunity in Macrobrachium rosenbergii. Five experimental diets were 1.0‰ Bovine lactoferricin (LCB1); 1.5‰ Bovine lactoferricin (LCB1.5); 2.0‰ Bovine lactoferricin (LCB2); 2.5‰ Bovine lactoferricin (LCB2.5); the control group, basal diet without Bovine lactoferricin. A total of 600 prawns were randomly assigned to 5 groups in triplicate in 15 tanks for an 8-week feeding trial. The results showed the final weight, weight gain rate, specific growth rate and survival rate of prawns in the treatment groups were significantly improved versus the control (P < 0.05). The feed conversion ratio was reduced significantly in treatment groups compared to the control (P < 0.05). Compared with the control, alkaline phosphatase (AKP), acid phosphatase (ACP), lysozyme (LZM), catalase (CAT), superoxide dismutase (SOD) activities in the hepatopancreas of the treatment groups were significantly enhanced, and malondialdehyde (MDA) content was reduced significantly (P < 0.05). Compared with the control, the relative expression levels of AKP, ACP, LZM, CAT, SOD, Hsp70, peroxiredoxin-5, Toll, dorsal and relish genes were significantly higher among treatment groups, except for the AKP gene in the LCB1 group and the Hsp70 gene in the LCB1.5 group (P < 0.05). Compared with the control, the relative expression levels of TOR, 4E-BP, eIF4E1α and eIF4E2 genes were significantly enhanced in the LCB1.5 group (P < 0.05). When resistance against Vibrio parahaemolyticus in prawn is considered, higher doses of Bovine lactoferricin show better antibacterial ability. The present study indicated that dietary Bovine lactoferricin could significantly improve the growth performance and improve the antioxidative status of M. rosenbergii. The suitable addition level is 1.5 g/kg. LFcinB has great potential as a new feed additive without the threat of drug resistance.

Transmission Power Control in Wireless Sensor Networks Using Fuzzy Adaptive Data Rate.

As the technology of Internet of Things (IoT) becomes popular, the number of sensor nodes also increases. The network coverage, extensibility, and reliability are also the key points of technical development. To address the challenge of environmental restriction and deployment cost, most sensor nodes are powered by batteries. Therefore, the low-power consumption becomes an important issue because of the finite value of battery capacity. In addition, significant interference occurs in the environment, thereby complicating reliable wireless communication. This study proposes a fuzzy-based adaptive data rate for the transmission power control in wireless sensor networks to balance the communication quality and power consumption. The error count and error interval perform the inputs of a fuzzy system and the corresponding fuzzy system output is guard that is utilized for limiting the upper bounds of data rate and transmission power. The long-term experimental results are introduced to demonstrate that the control algorithm can overcome environmental interference and obtain low-power performance. The sensor nodes have reliable communication under an ultra-low-power consumption. The experimental results show that the total power consumption of the proposed approach has been improved 73% compared with the system without executing the algorithm and also indicate the Packet Error Rate (PER) is close to 1%. Therefore, the proposed method is suitable for the battery supply IoT system.

Influence mechanisms of iron, aluminum and manganese oxides on the mineralization of organic matter in paddy soil.

The mineralization of soil organic matter (SOM) is closely related to the emission of greenhouse gas into atmosphere and the stability of organic carbon in soil. The influence of minerals on SOM mineralization in the specific soil received very few attentions. The influence characteristics and potential mechanisms of oxides on the mineralization of SOM in the paddy soil were observed in this study by incubating soil with the addition (dosage: 10 g kg-1) of prepared gibbsite, goethite, ferrihydrite or birnessite for 60 days. A sequence control treatment (753 mg CO2-C kg-1) > goethite treatment (656 mg CO2-C kg-1) ≈ gibbsite treatment (649 mg CO2-C kg-1) > birnessite treatment (529 mg CO2-C kg-1) > ferrihydrite treatment (441 mg CO2-C kg -1) was found in the cumulative amount of released CO2 in 60 days of incubation. Oxides especially ferrihydrite significantly decreased the content of dissolved organic matter (DOM) but tended to increase the content of microbial biomass carbon (MBC). The molecular structure of DOM in the paddy soil was simplified by gibbsite, ferrihydrite and birnessite after the incubation. Oxides especially birnessite and ferrihydrite reduced soil pH and the content of soil available N but increased soil redox potential (Eh). All examined oxides especially Fe oxides enhanced soil bacterial abundance but only birnessite significantly affected bacterial composition at phyla level. The stimulation on the immobilization and/or microbial assimilation of labile organic carbon, the modulation on soil basic properties (available N, pH, Eh), and the decrease of the relative abundance of some decomposing bacteria phyla such as Actinobacteria were the potential pathways of oxides in decreasing SOM mineralization.

[Research progress in chemical constituents, pharmacological activity, and quality markers of Bruceae Fructus].

Bruceae Fructus is a Chinese herbal medicine with the chemical constituents mainly including Brucea javanica oil, quassinoids, flavonoids, steroids, triterpenoids, and alkaloids. Modern research demonstrates that Bruceae Fructus has anti-tumor, anti-malaria, anti-inflammatory, and lipid-lowering activities. This paper introduces the resource distribution, chemical constituents, and pharmacological activities of Bruceae Fructus. Further, according to the concept of quality marker(Q-marker), this paper predicts the Q-markers of Bruceae Fructus from the specificity of chemical components, pharmaceutical activity, measurability of chemical constituents, compatibility, and clinical efficacy, aiming to provide a theoretical basis for establishing the quality standard of Bruceae Fructus.

[Effect of Pien Tze Huang against EV71].

This study aims to investigate the inhibitory effect of Pien Tze Huang(PZH) on enterovirus 71(EV71). To be speci-fic, chemiluminescence method was adopted to evaluate the toxicity of PZH to African green monkey kidney(Vero) cells and human rhabdomyosarcoma(RD) cells, and cytopathic effect(CPE) method to assess the inhibition on EV71-GFP reporter virus and EV71 C4 wild-type virus. The results showed that PZH had low cytotoxicity to Vero cells and RD cells, with the half-maximal cytotoxic concentration(CC_(50)) of about 0.691 3-0.879 2 mg·mL~(-1) for the two. In addition, PZH can effectively inhibit the replication of EV71 within the non-cytotoxic concentration range, and dose-dependently alleviate the cytopathic changes caused by virus infection, with the half-maximal effective concentration(EC_(50)) of 0.009 2-0.106 3 mg·mL~(-1). On the basis of the above results, the green fluorescent protein(GFP), indirect immunofluorescence assay(IFA), and median tissue culture infective dose(TCID_(50)) were employed to assess and verify the anti-EV71-GFP and anti-EV71 C4 activity of PZH. The results demonstrated that PZH can dose-dependently lower the expression of GFP by EV71-GFP and structural protein VP-1 by EV71 C4 and decrease the production of progeny infectious viruses. The EC_(50) of PZH for EV71-GFP and EV71 C4 was about 0.006 0-0.006 2 mg·mL~(-1) and 0.006 6-0.025 6 mg·mL~(-1), respectively. This study suggested that PZH may exert antiviral activity by acting on EV71 and interfering with the expression of VP-1. At the moment, there is still a lack of specific anti-EV71 drugs. This study proposed a new idea for the symptomatic treatment of EV71 infections such as hand-foot-mouth disease and verified an effective drug for the treatment of EV71 infections.

Energetics and structure of alanine-rich α-helices via adaptive steered molecular dynamics.

The energetics and hydrogen bonding profiles of the helix-to-coil transition were found to be an additive property and to increase linearly with chain length, respectively, in alanine-rich α-helical peptides. A model system of polyalanine repeats was used to establish this hypothesis for the energetic trends and hydrogen bonding profiles. Numerical measurements of a synthesized polypeptide Ac-Y(AEAAKA)kF-NH2 and a natural α-helical peptide a2N (1-17) provide evidence of the hypothesis's generality. Adaptive steered molecular dynamics was employed to investigate the mechanical unfolding of all of these alanine-rich polypeptides. We found that the helix-to-coil transition is primarily dependent on the breaking of the intramolecular backbone hydrogen bonds and independent of specific side-chain interactions and chain length. The mechanical unfolding of the α-helical peptides results in a turnover mechanism in which a 310-helical structure forms during the unfolding, remaining at a near constant population and thereby maintaining additivity in the free energy. The intermediate partially unfolded structures exhibited polyproline II helical structure as previously seen by others. In summary, we found that the average force required to pull alanine-rich α-helical peptides in between the endpoints-namely the native structure and free coil-is nearly independent of the length or the specific primary structure.

Engineered nanoparticle network models for autonomous computing.

Materials that exhibit synaptic properties are a key target for our effort to develop computing devices that mimic the brain intrinsically. If successful, they could lead to high performance, low energy consumption, and huge data storage. A 2D square array of engineered nanoparticles (ENPs) interconnected by an emergent polymer network is a possible candidate. Its behavior has been observed and characterized using coarse-grained molecular dynamics (CGMD) simulations and analytical lattice network models. Both models are consistent in predicting network links at varying temperatures, free volumes, and E-field (E⃗) strengths. Hysteretic behavior, synaptic short-term plasticity and long-term plasticity-necessary for brain-like data storage and computing-have been observed in CGMD simulations of the ENP networks in response to E-fields. Non-volatility properties of the ENP networks were also confirmed to be robust to perturbations in the dielectric constant, temperature, and affine geometry.

Building blocks for autonomous computing materials: Dimers, trimers, and tetramers.

Autonomous computing materials for data storage and computing offer an opportunity for next generation of computing devices. Patchy nanoparticle networks, for example, have been suggested as potential candidates for emulating neuronal networks and performing brain-like computing. Here, we use molecular dynamics (MD) simulations to show that stable dimers, trimers, and tetramers can be built from citrate capped gold nanoparticles (cit-AuNPs) linked by poly(allylamine hydrochloride) (PAH) chains. We use different lengths of PAHs to build polymer-networked nanoparticle assemblies that can emulate a complex neuronal network linked by axons of varying lengths. We find that the tetramer structure can accommodate up to 11 different states when the AuNP pairs are connected by either of two polymer linkers, PAH200 and PAH300. We find that the heavy AuNPs contribute to the assembly's structure stability. To further illustrate the stability, the AuNP-AuNP distances in dimer, trimer, and tetramer structures are reduced by steering the cit-AuNPs closer to each other. At different distances, these steered structures are all locally stable in a 10 ns MD simulation time scale because of their connection to the AuNPs. We also find that the global potential energy minimum is at short AuNP-AuNP distances where AuNPs collapse because the -NH3 + and -COO- attraction reduces the potential energy. The stability and application of these fundamental structures remain to be further improved through the use of alternative polymer linkers and nanoparticles.

Frequency, Risk Factors, and Outcome of Active Tuberculosis following Allogeneic Hematopoietic Stem Cell Transplantation.

We aimed to investigate the frequency, risk factors, and outcome of active tuberculosis (TB) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective, nested, case-control study reviewed data from 6236 patients who received allo-HSCT from January 2008 to December 2018 at a single center; thirty-three patients (0.5%) with active TB and 99 controls without active TB after allo-HSCT were identified. We performed propensity score matching by randomly selecting 3 controls for each identified active TB patient according to the time of transplantation and follow-up period. History of pretransplant active TB previously treated and inactive at time of transplantation (P< .001) was an independent risk factor. No significant differences in overall survival (P= .342), nonrelapse mortality (P= .497), or incidence of relapse (P= .807) were found. Thirty (90.9%) patients were treated with 4-drug (isoniazid, rifampicin/three rifapentine, pyrazinamide, and ethambutol) or 3-drug combination first-line therapy, with a response rate of 76.7%. Twenty-six (78.8%) patients were treated with first-line and second-line combined therapy, and the response rate was 76.9%. Five (15.2%) patients developed hepatotoxicity. In conclusion, history of pretransplant active TB previously treated and inactive at time of transplantation was an independent risk factor of active TB after allo-HSCT. No significant differences in prognosis between the TB and control groups were found. More studies are needed to help develop standardized therapeutic strategies for patients with post-transplant TB.

Surfactant protein D is associated with 3-month mortality of anti-MDA5 antibody-interstitial lung disease.

OBJECTIVES: To investigate the associations between serum levels of matrix metalloproteinase 7 (MMP7), surfactant protein D (SPD), interleukin 18 (IL-18) and chemokine ligand 18 (CCL18) with dermatomyositis and polymyositis-associated interstitial lung disease (DM/PM-ILD) and evaluate their prognostic values in the disease. METHODS: Seventy-eight patients with multiple disciplinary team diagnosis of DM/PM-ILD were enrolled and classified as anti-melanoma differentiation-associated protein 5 antibody (MDA5)-ILD, anti-synthetase antibodies (ARS)-ILD and other antibodies-ILD upon autoantibodies profiles. Clinical data were collected and serum levels of four biomarkers were analysed. The primary endpoint was 3-month mortality. The cut-off values of biomarkers for mortality were figured out by receiver operating characteristic (ROC) analysis. Cox regression was performed to evaluate predictive values. RESULTS: Serum levels of MMP7 (p=0.036), SPD (p<0.001), IL-18 (p<0.001) and CCL18 (p<0.001) in patients with DM/PM-ILD were significantly higher than healthy controls with levels of MMP7 (p=0.029) and SPD (p=0.029) in patients with MDA5-ILD significantly lower than patients with ARS-ILD. The 3-month mortality in MDA5-ILD was 54.5% (12/22). Multivariate analysis showed that age (p=0.001, HR 1.151, 95% CI 1.063-1.247) and an increased level of SPD (>75.90ng/ml, p=0.005, HR 16.411, 95% CI 2.369-113.711) were significant predictors for 3-month mortality in patients with MDA5-ILD. CONCLUSIONS: Elevated serum biomarkers were associated with DM/PM-ILD with differential levels between MDA5-ILD and ARS-ILD. Age and an increased SPD had prognostic values for predicting short-term mortality in patients with MDA5-ILD. Our study was important in providing a clue for understanding the classification and prognosis of DM/PM-ILD.

Three­Dimensional Ultrasonography in Preoperative and Postoperative Volume Assessment of the Undescended Testicle.

BACKGROUND Ultrasound (US) is the preferred imaging method for cryptorchidism, but most guidelines indicate that its value is questionable. The aim of this study was to evaluate the clinical value of ultrasonic mobility and testicular atrophy index (TAI) based on three­dimensional US (3DUS) in preoperative and postoperative assessment of the undescended testis. MATERIAL AND METHODS Data from 158 children with unilateral extraperitoneal cryptorchidism were collected and their diagnoses were surgically confirmed. They were divided into different age groups and into 2 ultrasonic mobility groups: the mobile group (MG) and the restricted group (RG). Differences in sonographic characteristics between different groups were compared. Three-dimensional ultrasound performed with virtual organ computer-aided analysis (VOCAL) was used to determined preoperative and postoperative TAI and the reliability of TAI was analyzed. RESULTS Measurement of testicular volume with the VOCAL method was significantly more reliable than that done with the two-dimensional Lambert method. In all age groups, preoperative testicular volumes were smaller than that in the contralateral scrotal testis and postoperatively, they increased steadily. Both preoperative and postoperative TAI were higher in the RG than in the MG. In the MG, postoperative TAI decreased significantly in all age groups. In the RG, in contrast, effective volume growth was only achieved in patients who had undergone surgery before they reached age 1 year. CONCLUSIONS TAI values determined with 3DUS using the VOCAL technique objectively reflect recovery of testicular volume following surgery for undescended testicle. Ultrasonic mobility evaluation is beneficial for clinical management of the condition.