PfAgo-Based Zika Virus Detection.

As a mosquito-borne flavivirus, Zika virus (ZIKV) has been identified as a global health threat. The virus has been linked to severe congenital disabilities, including microcephaly and other congenital malformations, resulting in fatal intrauterine death. Therefore, developing sensitive and specific methods for the early detection and accurate diagnosis of the ZIKV is essential for controlling its spread and mitigating its impact on public health. Herein, we set up a novel nucleic acid detection system based on Pyrococcus furiosus Argonaute (PfAgo)-mediated nucleic acid detection, targeting the non-structural protein 5 (NS5) region of the ZIKV genome (abbreviated ZIKV-PAND). Without preamplification with the polymerase chain reaction (PCR), the minimum detection concentration (MDC) of ZIKV-PAND was about 10 nM. When introducing an amplification step, the MDC can be dramatically decreased to the aM level (8.3 aM), which is comparable to qRT-PCR assay (1.6 aM). In addition, the diagnostic findings from the analysis of simulated clinical samples or Zika virus samples using ZIKV-PAND show a complete agreement of 100% with qRT-PCR assays. This correlation can aid in the implementation of molecular testing for clinical diagnoses and the investigation of ZIKV infection on an epidemiological scale.

Resveratrol prevents age-related heart impairment through inhibiting the Notch/NF-κB pathway.

Resveratrol (RSV) is a natural polyphenol compound found in various plants that has been shown to have potential benefits for preventing aging and supporting cardiovascular health. However, the specific signal pathway by which RSV protects the aging heart is not yet well understood. This study aimed to explore the protective effects of RSV against age-related heart injury and investigate the underlying mechanisms using a D-galactose-induced aging model. The results of the study indicated that RSV provided protection against age-related heart impairment in mice. This was evidenced by the reduction of cardiac histopathological changes as well as the attenuation of apoptosis. RSV-induced cardioprotection was linked to a significant increase in antioxidant activity and mitochondrial transmembrane potential, as well as a reduction in oxidative damage. Additionally, RSV inhibited the production of pro-inflammatory cytokines such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). Furthermore, the expression of toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κB p65), and notch 1 protein were inhibited by RSV, indicating that inhibiting the Notch/NF-κB pathway played a critical role in RSV-triggered heart protection in aging mice. Moreover, further data on intestinal function demonstrated that RSV significantly increased short-chain fatty acids (SCFAs) in intestinal contents and reduced the pH value in the feces of aging mice. RSV alleviated aging-induced cardiac dysfunction through the suppression of oxidative stress and inflammation via the Notch/NF-κB pathway in heart tissue. Furthermore, this therapeutic effect was found to be associated with its protective roles in the intestine.

Time-varying and speed-matched model for the evaluation of stroke-induced changes in ankle mechanics.

The ankle mechanics (stiffness and moment) are modulated continuously when interacting with the environment during human walking. However, it remains unclear how ankle mechanics vary with walking speeds, and how they are affected by stroke. This study aimed to determine time-varying ankle stiffness and moment in stroke participants during walking, comparing them with healthy participants at matched speeds. A motion capture system, surface electromyography (EMG) system and force plates were used to measure biomechanics of seven healthy participants walking at 5 controlled speeds and ten patients with stroke at self-selected speeds. The ankle moment and stiffness during the stance phase were calculated using an EMG-driven musculoskeletal model. Surface equations of ankle moment and stiffness in healthy participants, with walking speed and stance phase as variables, were proposed based on polynomial fitting. Results showed that as walking speed increased, there was an increase in the ankle stiffness and moment of healthy participants during 77 %-89 % and 63 %-91 % of stance phase, respectively. Patients with stroke had lower ankle stiffness and moment at self-selected walking speed than healthy participants at 1.04 m/s walking speed during 52 %-87 % and 52 %-91 % of stance phase, respectively. At matched walking speed, the peak values of ankle stiffness and moment in patients with stroke were significantly less than those in healthy participants (p = 0.007; p = 0.028, respectively). This study proposes a novel approach to evaluate the ankle mechanics of patients with stroke using the speed-matched model of healthy participants and may provide insights into understanding speed-dependent movement mechanisms of human walking.

Age-related differences in the capacity and neuromuscular control of the foot core system during quiet standing.

The foot core system is essential for upright stability. However, aging-induced changes in the foot core function remain poorly understood. The present study aimed to examine age-related differences in postural stability from the perspective of foot core capacity and neuromuscular control during quiet standing. Thirty-six older and 25 young adults completed foot core capacity tests including toe flexion strength, muscle ultrasonography, and plantar cutaneous sensitivity. The center of pressure (COP) and electromyography (EMG) of abductor hallucis (ABH), peroneus longus (PL), tibialis anterior (TA) and medial gastrocnemius (GM) were simultaneously recorded during double-leg and single-leg standing (SLS). EMG data were used to calculate muscle synergy and intermuscular coherence across three frequency bands. Compared to young adults, older adults exhibited thinner hallucis flexors, weaker toe strength, and lower plantar cutaneous sensitivity. The ABH thickness and plantar cutaneous sensitivity were negatively associated with the COP mean peak velocity in older adults, but not in young adults. Besides, older adults had higher cocontraction of muscles spanning the arch (ABH-PL) and ankle (TA-GM), and had lower beta- and gamma-band coherence of the ABH-PL and TA-PL during SLS. Foot core capacities became compromised with advancing age, and the balance control of older adults was susceptible to foot core than young adults in balance tasks. To compensate for the weakened foot core, older adults may adopt arch and ankle stiffening strategies via increasing muscle cocontraction. Furthermore, coherence analysis indicated that aging may increase the demand for cortical brain resources during SLS.

The impact of aggregation of AIE and ACQ moiety-integrating material on the excited state dynamics.

The investigation of the properties of aggregate materials is highly interesting because the process of aggregation can result in the disappearance of original properties and the emergence of new ones. Here, a novel fluorescent material (TPEIP), which synergistically combines aggregation-induced emission (AIE) and aggregation caused quenching (ACQ) moieties, was first synthesized by the cyclization reaction of 2,3-diamino-phenazine with 4-tetraphenylenthenealdehyde. We controlled the degree of aggregation of TPEIP to shed light on the impact of the aggregation on the excited state dynamics. TPEIP aggregation realized control over the Intersystem Crossing (ISC) rates and, in turn, the suppression of triplet excited states in MeOH, EtOH or via the simple addition of water to TPEIP solutions in DMSO. From global target analysis, the time scale was 966.2 ps for ISC for TPEIP in DMSO, but it was 860 ps in the case of TPEIP solutions featuring 5% water. The dynamics of TPEIP excited states undergo significant changes as the degree of aggregation increases. Notably, the lifetime of singlet excited states decreases, and there was a gradual diminishment in triplet states.

The gut and lung microbiota in pulmonary tuberculosis: susceptibility, function, and new insights into treatment.

INTRODUCTION: Tuberculosis (TB) is a chronic infectious disease caused by mycobacterium tuberculosis (Mtb) that poses a major threat to human health. AREAS COVERED: Herein, we aim to review the alteration of the microbiota in gut and respiratory during TB development, the potential function and mechanisms of microbiota in the pathogenesis of Mtb infection, and the impact of antibiotic treatment on the microbiota. In addition, we discuss the potential new paradigm for the use of microbiota-based treatments such as probiotics and prebiotics in the treatment of TB. EXPERT OPINION: Studies have shown that trillions of micro-organisms live in the human gut and respiratory tract, acting as gatekeepers in maintaining immune homeostasis and respiratory physiology and playing a beneficial or hostile role in the development of TB. Anti-TB antibiotics may cause microecological imbalances in the gut and respiratory tract, and microbiome-based therapeutics may be a promising strategy for TB treatment. Appropriate probiotics and prebiotics supplementation, along with antimycobacterial treatment, will improve the therapeutic effect of TB treatment and protect the gut and respiratory microbiota from dysbiosis.

Simultaneous quantitative chiral analysis of four isomers by ultraviolet photodissociation mass spectrometry and artificial neural network.

Although mass spectrometry (MS) has its unique advantages in speed, specificity and sensitivity, its application in quantitative chiral analysis aimed to determine the proportions of multiple chiral isomers is still a challenge. Herein, we present an artificial neural network (ANN) based approach for quantitatively analyzing multiple chiral isomers from their ultraviolet photodissociation mass spectra. Tripeptide of GYG and iodo-L-tyrosine have been applied as chiral references to fulfill the relative quantitative analysis of four chiral isomers of two dipeptides of L/D His L/D Ala and L/D Asp L/D Phe, respectively. The results show that the network can be well-trained with limited sets, and have a good performance in testing sets. This study shows the potential of the new method in rapid quantitative chiral analysis aimed at practical applications, with much room for improvement in the near future, including selecting better chiral references and improving machine learning methods.

Hybrid adiabatic pulse with asymmetry (HAPY): An asymmetric adiabatic pulse with an application in pulsed arterial spin labeling at 7T.

PURPOSE: A new class of asymmetric adiabatic radiofrequency (RF) pulses, Hybrid Adiabatic Pulse with asYmmetry (HAPY), is designed to be used as the labeling pulse for Pulsed Arterial Spin labeling (PASL) at 7T to reduce overall specific absorption rate (SAR) while maintaining high labeling efficiency with B 0 $$ {\mathrm{B}}_0 $$ and B 1 + $$ {\mathrm{B}}_1^{+} $$ inhomogeneities. METHODS: Realistic Δ B 0 $$ \Delta {\mathrm{B}}_0 $$ and B 1 + $$ {\mathrm{B}}_1^{+} $$ distributions were extracted from multiple in vivo scans. The proposed class of asymmetric pulses was parameterized and optimized considering these conditions. Simulation and phantoms experiments were performed to compare the optimized pulses with HS-3, GOIA, and trFOCI pulses. In vivo experiments were conducted to demonstrate the application of HAPY in PICORE PASL at 7T, compared with the GOIA and trFOCI pulses. RESULTS: HAPYs with different amounts of pulse energy reduction are obtained by the proposed optimization framework. Both simulation and phantom experiments demonstrate that HAPY achieves high labeling efficiency and high selectivity along the critical side despite B 0 $$ {\mathrm{B}}_0 $$ off-resonance and low B 1 + $$ {\mathrm{B}}_1^{+} $$ amplitude. In vivo experiments reveal that HAPY is able to generate robust perfusion signal with less overall SAR or shorter pulse repetition time, compared to the GOIA and trFOCI pulses. CONCLUSION: The HAPY class of pulses, obtained via systematic optimization tailored to the application of PASL at 7T, reduces power deposition without affecting labeling efficiency, which provides a prospect of further exploiting the benefits of ultra-high field in ASL.

Effects of arch support doses on the center of pressure and pressure distribution of running using statistical parametric mapping.

Insoles with an arch support have been used to address biomechanical risk factors of running. However, the relationship between the dose of support and running biomechanics remains unclear. The purpose of this study was to determine the effects of changing arch support doses on the center of pressure (COP) and pressure mapping using statistical parametric mapping (SPM). Nine arch support variations (3 heights * 3 widths) and a flat insole control were tested on fifteen healthy recreational runners using a 1-m Footscan pressure plate. The medial-lateral COP (COPML) coordinates and the total COP velocity (COPVtotal) were calculated throughout the entirety of stance. One-dimensional and two-dimensional SPM were performed to assess differences between the arch support and control conditions for time series of COP variables and pressure mapping at a pixel level, respectively. Two-way ANOVAs were performed to test the main effect of the arch support height and width, and their interaction on the peak values of the COPVtotal. The results showed that the COPVtotal during the forefoot contact and forefoot push off phases was increased by arch supports, while the COP medial-lateral coordinates remained unchanged. There was a dose-response effect of the arch support height on peak values of the COPVtotal, with a higher support increasing the first and third valleys but decreasing the third peak of the COPVtotal. Meanwhile, a higher arch support height shifted the peak pressure from the medial forefoot and rearfoot to the medial arch. It is concluded that changing arch support doses, primarily the height, systematically altered the COP velocities and peak plantar pressure at a pixel level during running. When assessing subtle modifications in the arch support, the COP velocity was a more sensitive variable than COP coordinates. SPM provides a high-resolution view of pressure comparisons, and is recommended for future insole/footwear investigations to better understand the underlying mechanisms and improve insole design.

Symptomatic and asymptomatic pronated feet show differences in the forefoot abduction motion during jogging, but not in the arch deformation.

Pronated feet have been associated with higher risks of running-related overuse injuries than neutral feet. However, it remains unclear why some pronated feet develop running-related injuries, while others do not. This study aimed to examine the differences in foot kinematics during jogging among individuals with symptomatic pronated feet (SP), asymptomatic pronated feet (AP) and asymptomatic neutral feet (AN). Thirty-nine recreational runners were recruited and classified into the SP, AP and AN groups. Statistical parametric mapping (SPM) and ANOVA were used to identify kinematic differences among three groups. The SPM results showed that the SP had larger forefoot abduction than the AN and AP during jogging, while three groups had similar rearfoot eversion during jogging. Both the AP and SP had larger forefoot sagittal range of motion (ROM) (mean difference = 3.5 and 4.8 deg, respectively) and smaller rearfoot sagittal ROM (mean difference = 5.0 and 3.5 deg, respectively) than the AN. Forefoot abduction during jogging may have the potential to identify pronated feet at greater risk of injury. Pronated feet, symptomatic or not, have comparable large forefoot sagittal ROM, i.e., arch deformation, compared to neutral feet. The findings could have implications for the injury aetiology and intervention strategies for SP.

Comprehensive identification of immuno-related transcriptional signature for active pulmonary tuberculosis by integrated analysis of array and single cell RNA-seq.

BACKGROUND: Tuberculosis (TB) continues to be a major cause of morbidity and mortality worldwide. However, the molecular mechanism underlying immune response to human infection with Mycobacterium tuberculosis (Mtb) remains unclear. Assessing changes in transcript abundance in blood between health and disease on a genome-wide scale affords a comprehensive view of the impact of Mtb infection on the host defense and a reliable way to identify novel TB biomarkers. METHODS: We combined expression profiling by array and single cell RNA-sequencing (scRNA-seq) via 10X Genomics platform to better illustrate the immuno-related transcriptional signature of TB and explore potential diagnostic markers for differentiating TB from latent tuberculosis infection (LTBI) and healthy control (HC). FINDINGS: Pathway analysis based on differential expressed genes (DEGs) revealed that immune transcriptional profiling could effectively differ TB with LTBI and HC. Following WGCNA and PPI network analysis based on DEGs, we screened out three key immuno-related hub genes (ADM, IFIT3 and SERPING1) highly associated with TB. Further validation found only ADM expression significantly increased in TB patients in both adult and children's datasets. By comparing the scRNA-seq datasets from TB, LTBI and HC, we observed a remarkable elevated expression level and proportion of ADM in TB Myeloid cells, further supporting that ADM expression changes could distinguish patients with TB from LTBI and HC. Besides, the hsa-miR-24-3p-NEAT1-ADM-CEBPB regulation pathway might be one of the critical networks regulating the pathogenesis of TB. Although further investigation in a larger cohort is warranted, we provide useful and novel insight to explore the potential candidate genes for TB diagnosis and intervention. INTERPRETATION: We propose that the expression of ADM in peripheral blood could be used as a novel biomarker for differentiating TB with LTBI and HC.

Long Non-coding RNAs in Tuberculosis: From Immunity to Biomarkers.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is the leading lethal infectious disease with 1.3 million deaths in 2020. Despite significant advances have been made in detection techniques and therapeutic approaches for tuberculosis, no suitable diagnostic tools are available for early and precise screening. Many studies have reported that Long non-coding RNAs (lncRNAs) play a regulatory role in gene expression in the host immune response against Mtb. Dysregulation of lncRNAs expression patterns associated with immunoregulatory pathways arose in mycobacterial infection. Meanwhile, host-induced lncRNAs regulate antibacterial processes such as apoptosis and autophagy to limit bacterial proliferation. In this review, we try to summarize the latest reports on how dysregulated expressed lncRNAs influence host immune response in tuberculosis infection. We also discuss their potential clinical prospects for tuberculosis diagnosis and development as molecular biomarkers.

A novel method for photon unfolding spectroscopy of protein ions in the gas phase.

In this study, a new experimental method for photon unfolding spectroscopy of protein ions based on a Fourier transform ion cyclotron resonance (FT ICR) mass spectrometer was developed. The method of short-time Fourier transform has been applied here to obtain decay curves of target ions trapped in the cell of the FT ICR mass spectrometer. Based on the decay constants, the collision cross sections (CCSs) of target ions were calculated using the energetic hard-sphere model. By combining a tunable laser to the FT ICR mass spectrometer, the changes of CCSs of the target ions were recorded as a function of the wavelengths; thus, the photon isomerization spectrum was obtained. As one example, the photon isomerization spectrum of [Cyt c + 13H]13+ was recorded as the decay constants relative to the applied wavelengths of the laser in the 410-480 nm range. The spectrum shows a maximum at 426 nm, where an unfolded structure induced by a 4 s irradiation can be deduced. The strong peak at 426 nm was also observed for another ion of [Cyt c + 15H]15+, although some difference at 410 nm between the two spectra was found at the same time. This novel method can be expanded to ultraviolet or infrared region, making the experimental study of wavelength-dependent photon-induced structural variation of a variety of organic or biological molecules possible.

Dose-response effects of forefoot and arch orthotic components on the center of pressure trajectory during running in pronated feet.

BACKGROUND: Foot orthoses are widely used in runners with pronated feet, who are characterized with large forefoot abduction and arch deformation during gait. However, the relationship between the amount of forefoot and arch orthotic correction and the alterations in foot biomechanics remains unclear. RESEARCH QUESTION: This study aimed to determine dose-response effects of foot orthoses with forefoot wedge and arch support components on the center of pressure (COP) trajectories and pressure distribution during running in symptomatic pronated feet. METHODS: Fifteen recreational runners participated in this study. A pressure plate was used to measure plantar pressures during running with control shoe only and ten foot orthoses, varying in forefoot wedges (5 levels) and arch supports (2 levels). The COP trajectory across the entire stance phase was compared between orthotic and control conditions using one-dimensional statistical parametric mapping. The differences in the force-time integral (FTI) and temporal variables were explored between conditions using repeated measures ANOVAs. The main effect of the two orthotic components and their interaction on tested variables were examined using two-way ANOVAs. RESULTS: A forefoot wedge, whether laterally or medially located, shifted the COP trajectory laterally during some subphases of running (p < 0.05), while using an arch support only had minimal effect on the COP. Almost all orthoses reduced the FTI on the 2nd metatarsal and medial heel, and only medial forefoot wedges reduced the FTI on the hallux. There was a linear effect of forefoot wedges on the medial-lateral COP displacements during the propulsion phase, but no interactions were found between two orthotic components. SIGNIFICANCE: These findings suggest that forefoot orthotic components rather than arch supports are effective in altering forefoot dynamics in runners with pronated feet. This study could have implications for foot orthotic prescription and running-related injury prevention for individuals with pronated feet.

Immediate effects of forefoot wedges on multi-segment foot kinematics during jogging in recreational runners with a symptomatic pronated foot.

Background: Foot orthoses (FOs) have been used to alter lower limb kinematics and kinetics in pronated feet. A clear relationship between FOs' features, e.g., the amount of wedging and support, and the corresponding biomechanical responses is vital for the design and prescription of FOs. In this study, we sought to determine if changing the level of the forefoot wedge would cause a linear response in the multi-segment foot kinematics during jogging, and if this effect would be enhanced by an arch support. Methods: Ten pairs of 3D printed FOs with five levels of forefoot wedges and two levels of arch supports were tested on 12 recreational runners with a symptomatic pronated foot. Multi-segment foot kinematic data during jogging was measured using the Oxford Foot Model. Two-way ANOVAs were performed to examine the main effect of the forefoot wedge and arch support, as well as their interaction on peak joint angles. Statistical parametric mapping and paired-t tests were used to identify differences in the foot kinematic traces and the joint range of motion (ROM) between each FO and the control, respectively. Results: Linear main effects for the forefoot wedge level were found in the forefoot peak dorsiflexion, eversion and rearfoot peak dorsiflexion of jogging. FOs with a medial forefoot wedge caused an average of 2.5° reduction of the forefoot peak abduction during jogging. Furthermore, forefoot wedges showed an opposite effect on the sagittal ROM of the forefoot and rearfoot. Adding an arch support did not improve the kinematic performance of a forefoot wedge during jogging. Conclusion: This study highlights a linear dose-response effect of a forefoot wedge on forefoot kinematics during jogging, and suggests using a medial forefoot wedge as an anti-pronator component for controlling forefoot motion of a pronated foot.

Self-Assembly of [3]Catenane and [4]Catenane Based on Neutral Organometallic Scaffolds.

Transition metal-mediated templating and self-assembly have shown great potential to construct mechanically interlocked molecules. Herein, we describe the formation of the bimetallic [3]catenane and [4]catenane based on neutral organometallic scaffolds via the orthogonality of platinum-to-oxygen coordination-driven self-assembly and copper(I) template-directed strategy of a [2]pseudorotaxane. The structures of these bimetallic [3]catenane and [4]catenane were characterized by multinuclear NMR {1H and 31P} spectroscopy, electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS), and PM6 semiempirical molecular orbital theoretical calculations. In addition, single-crystal X-ray analyses of the [3]catenane revealed two asymmetric [2]pseudorotaxane units inside the metallacycle. It was discovered that tubular structures were formed through the stacking of individual [3]catenane molecules driven by the strong π-π interactions.

How Compliance of Surfaces Affects Ankle Moment and Stiffness Regulation During Walking.

Humans can regulate ankle moment and stiffness to cope with various surfaces during walking, while the effect of surfaces compliance on ankle moment and stiffness regulations remains unclear. In order to find the underlying mechanism, ten healthy subjects were recruited to walk across surfaces with different levels of compliance. Electromyography (EMG), ground reaction forces (GRFs), and three-dimensional reflective marker trajectories were recorded synchronously. Ankle moment and stiffness were estimated using an EMG-driven musculoskeletal model. Our results showed that the compliance of surfaces can affect both ankle moment and stiffness regulations during walking. When the compliance of surfaces increased, the ankle moment increased to prevent lower limb collapse and the ankle stiffness increased to maintain stability during the mid-stance phase of gait. Our work improved the understanding of gait biomechanics and might be instructive to sports surface design and passive multibody model development.

Three-dimensional MR Elastography Depicts Liver Inflammation, Fibrosis, and Portal Hypertension in Chronic Hepatitis B or C.

Background The value of measuring mechanical properties to categorize various pathophysiologic states of the liver is as yet undetermined in chronic hepatitis B (CHB) or C (CHC). Purpose To evaluate multiparametric three-dimensional (3D) MR elastography as a means of detecting early necroinflammation, distinguishing necroinflammation from fibrosis, and gauging the severity of portal hypertension (PH) in CHB or CHC. Materials and Methods From January 2015 to September 2019, participants with CHB or CHC were prospectively enrolled from a single institution and were divided into two groups: those with liver biopsy and no evidence of PH (group 1) and those with PH and a hepatic venous pressure gradient (HVPG) measurement (group 2). For group 3, healthy volunteers were separately recruited from a nearby community. Multiple viscoelastic parameters (shear stiffness [SS], storage modulus, loss modulus, and damping ratio [DR]) were determined at 3D MR elastography at 60 Hz, and multivariable logistic or linear regression analysis was used to assess associations of mechanical parameters with histologic scores and HVPG. Results A total of 155 participants (median age, 41 years [interquartile range, 32-48 years]; 85 women) were in group 1 (training set: n = 78, validation set: n = 77), 85 participants (median age, 57 years [interquartile range, 43-61 years]; 51 women) in group 2, and 60 healthy volunteers (median age, 49 years [interquartile range, 27-64 years]; 38 men) in group 3. The liver DR was higher in participants with necroinflammation (DR, 0.13 ± 0.03) versus those without (at liver fibrosis stage F0) (DR, 0.10 ± 0.02; P < .001). Liver DR and SS together performed well in the diagnosis of necroinflammation (area under the receiver operating characteristic curve [AUC], 0.88 [95% CI: 0.79, 0.96]) and the scoring of moderate to severe activity (AUC, 0.88 [95% CI: 0.81, 0.95]) in the validation data set. Liver DR (regression coefficient [ß] = -30.3 [95% CI: -58.0, -2.5]; P = .03) and splenic SS (ß = 2.3 [95% CI: 1.7, 2.9]; P < .001) were independently associated with HVPG. Conclusion Three-dimensional MR elastography may detect early necroinflammation, distinguish necroinflammation from liver fibrosis, and correlate with hepatic venous pressure gradient in chronic hepatitis B and C. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Reeder in this issue.

Search for Global Minimum Structures of P 2 n + 1 + (n = 1-15) Using xTB-Based Basin-Hopping Algorithm.

A new program for searching global minimum structures of atomic clusters using basin-hopping algorithm based on the xTB method was developed here. The program can be performed with a much higher speed than its replacement directly based on DFT methods. Considering the structural varieties and complexities in finding their global minimum structures, phosphorus cluster cations were studied by the program. The global minimum structures of cationic P 2 n + 1 + (n = 1-15) clusters are determined through the unbiased structure searching method. In the last step, further DFT optimization was performed for the selected isomers. For P 2 n + 1 + (n = 1-4, 7), the found global minimum structures are in consistent with the ones previously reported; while for P 2 n + 1 + (n = 5, 6, 8-12), newly found isomers are more energy-favorable than those previously reported. And those for P 2 n + 1 + (n = 13-15) are reported here for the first time. Among them, the most stable isomers of P 2 n + 1 + (n = 4-6, 9) are characterized by their C3v, Cs, C2v and Cs symmetry, in turn. But those of P 2 n + 1 + (n = 7, 8, 10-12), no symmetry has been identified. The most stable isomers of P 29 + and P 31 + are characterized by single P-P bonds bridging units inside the clusters. Further analysis shows that the pnicogen bonds play an important role in the stabilization of these clusters. These results show that the new developed program is effective and robust in searching global minimum structures for atom clusters, and it also provides new insights into the role of pnicogen bonds in phosphorus clusters.

Autophagy-related genes contribute to malignant progression and have a clinical prognostic impact in colon adenocarcinoma.

Autophagy has an important role in regulating tumor cell survival. However, the roles of autophagy-related genes (ARGs) during colon adenocarcinoma (COAD) progression and their prognostic value have remained elusive. The present study aimed to identify the correlation between ARGs and the progression of COAD, as well as the prognostic significance of ARGs. The transcriptome profiles and the corresponding clinicopathological information of patients with COAD were downloaded from The Cancer Genome Atlas and Genotype-Tissue Expression databases. A list of ARGs was obtained from the Human Autophagy Database and bioinformatics analysis was performed to investigate the functions of these ARGs. Statistical analyses of these genes were performed to identify independent prognostic markers. The selected prognostic markers were then validated in 15 patients with COAD via immunohistochemistry. Differentially expressed ARGs between normal and tumor tissues were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that the differentially expressed ARGs were mainly enriched in toxoplasmosis and pathways in cancer. The ATG4B, DAPK1 and SERPINA1 genes were determined to be associated with COAD progression. In addition, a risk signature was proposed that may serve as an independent prognostic marker. In conclusion, ATG4B, DAPK1 and SERPINA1 are crucial participants in tumorigenesis of COAD. The present study may promote the development of novel treatment strategies for COAD.