Correction to "Proppant Settlement and Long-Term Conductivity Calculation in Complex Fractures".

[This corrects the article DOI: 10.1021/acsomega.3c08594.].

Sigmoid colon cancer presenting as a large abdominal mass accompanied by abscess and rupture: a case report and literature review.

Introduction and Importance: Colon cancer presenting as a large abdominal mass accompanied by abscess and rupture is rare and prone to be misdiagnosed and delayed. In addition, the treatment plan is not clear when combined with abdominal wall metastasis. Case Presentation: A 79-year-old woman presented with a large abdominal mass accompanied by abscess and rupture. It was misdiagnosed as a soft tissue infection in a local hospital, and after a comprehensive examination, it was diagnosed as sigmoid colon cancer with abdominal wall metastasis and abscess formation. The patient underwent a one-stage surgery, including en bloc resection of the tumor and invaded abdominal wall, as well as autologous tissue abdominal wall reconstruction, with a good clinical prognosis. Clinical Discussion: For the diagnosis of large abdominal masses, abdominal CT, and pus culture are more valuable than ultrasound. For colon cancer with abdominal wall metastasis, one-stage surgery to completely remove the tumor and full-thickness of the abdominal wall, and the use of autologous tissue abdominal wall reconstruction technology to repair defects is feasible. Conclusion: This case highlights the importance of using colon cancer as one of the differential diagnoses for the diagnosis for large abdominal mass accompanied by abscess and rupture in elderly patients, as well as the possibility of one-stage surgical resection of the tumor and invasion of the abdominal wall and reconstruction of the abdominal wall with autologous tissue when there is abdominal wall metastasis.

Artificial Meshed Vessel-Induced Dimensional Breaking Growth of Human Brain Organoids and Multiregional Assembloids.

Brain organoids are widely used to model brain development and diseases. However, a major challenge in their application is the insufficient supply of oxygen and nutrients to the core region, restricting the size and maturation of the organoids. In order to vascularize brain organoids and enhance the nutritional supply to their core areas, two-photon polymerization (TPP) 3D printing is employed to fabricate high-resolution meshed vessels in this study. These vessels made of photoresist with densely distributed micropores with a diameter of 20 µm on the sidewall, are cocultured with brain organoids to facilitate the diffusion of culture medium into the organoids. The vascularized organoids exhibit dimensional breaking growth and enhanced proliferation, reduced hypoxia and apoptosis, suggesting that the 3D-printed meshed vessels partially mimic vascular function to promote the culture of organoids. Furthermore, cortical, striatal and medial ganglionic eminence (MGE) organoids are respectively differentiated to generate Cortico-Striatal-MGE assembloids by 3D-printed vessels. The enhanced migration, projection and excitatory signaling transduction are observed between different brain regional organoids in the assembloids. This study presents an approach using TPP 3D printing to construct vascularized brain organoids and assembloids for enhancing the development and assembly, offering a research model and platform for neurological diseases.

MRI Assessment of Diastolic Dysfunction in People Living With the Human Immunodeficiency Virus: Correlation With Markers of Disease Activity.

BACKGROUND: Despite the advent of combination antiretroviral therapy, people living with human immunodeficiency virus (PLWH) are at an increased risk for cardiac disease. PURPOSE: To explore the presence and extent of diastolic atrial and left ventricular dysfunction in PLWH using cardiac MRI in correlation with clinical markers of disease activity. STUDY TYPE: Prospective. POPULATION: A total of 163 participants comprising 101 HIV-infected individuals (age: 52 years [42-62 years]; 92% male) and 62 age- and sex-matched healthy volunteers (age: 51 years [30-72 years]; 85% male). FIELD STRENGTH/SEQUENCE: 3.0 T, cardiac MRI including balanced steady-state free precession (SSFP) for the short-axis, two-, three-, and four-chamber views were performed. ASSESSMENT: Assessment of cardiac function and strain analysis were accomplished by CVI42 software. Blood samples for CD4+ T cells and cardiac risk factors were also collected before MRI. STATISTICAL TESTS: Independent t tests, Mann-Whitney U test, Pearson's correlation analysis, and multivariate linear analyses (significance level: P < 0.05). RESULTS: PLWH had a significantly larger left atrial volume maximum index (LAVImax: 32.6 ± 8.7 vs. 28.7 ± 8.1 mL/m2), minimum (LAVImin: 14.8 ± 5.5 vs. 11.5 ± 5.4 mL/m2,), and prior to atrial contraction (LAVIpre-a: 23.4 ± 6.7 vs. 19.7 ± 7.2 mL/m2) as compared to healthy volunteers. The LA reservoir (LAtEF: 55.0 ± 10.2 vs. 61.4 ± 10.4; Sls: 29.0 ± 8.1 vs. 33.8 ± 11.8), conduit (LApEF: 28.4 ± 8.2 vs. 32.3 ± 11.3, P = 0.01; Sle: 16.3 ± 6.5 vs. 18.9 ± 8.2), and booster pump function (LAaEF: 37.4 ± 12.4 vs. 42.7 ± 13.1, P = 0.01, Sla: 12.7 ± 5.1 vs. 14.9 ± 5.7) were all significant impaired in PLWH. Global circumferential left ventricular diastolic strain rate (LVGCS-d) was significantly lower in the HIV patients. Multivariate analysis results showed that Nadir CD4+ T cells had a significant adverse association with LVGCS-d (ß = 0.51). CONCLUSION: LA structure abnormalities and LV diastolic dysfunction were manifested in PLWH, with Nadir CD4+ T cell counts potentially serving as a risk factor for early cardiac diastolic dysfunction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Quantification of subclinical plaque characteristics and perivascular fat using coronary computed tomography angiography (CCTA) among individuals with human immunodeficiency virus (HIV).

Background: People infected with human immunodeficiency virus (PIWH) have a higher risk of cardiovascular events. This study was designed to compare the differences in plaque characteristics and perivascular fat between subclinical coronary atherosclerosis in PIWH and healthy controls (HC) by coronary computed tomography angiography (CCTA). We also assessed the associations between human immunodeficiency virus (HIV) infection, antiretroviral therapy (ART), and coronary artery disease (CAD). Methods: This cross-sectional study included a total of 158 PIWH and 79 controls. CCTA was used to evaluate coronary artery plaque prevalence, coronary stenosis severity, plaque composition, plaque volume, and perivascular fat attenuation index (FAI). Logistic regression analyses were used to assess the associations between the prevalence of coronary artery plaque and HIV-related clinical indicators. Results: There was no difference in total coronary artery plaque prevalence between PIWH and controls (44.3% vs. 32.9%; P=0.09), but the prevalence of noncalcified plaque was significantly higher in PIWH compared with the controls (33.5% vs. 16.5%; P=0.006). After adjustment for age, sex, statin use, and family history of cardiovascular disease (CVD), the prevalence of noncalcified plaque remained 2 times higher in PIWH [odds ratio (OR), 2.082; 95% confidence interval (CI): 1.007-4.304; P=0.048]. The perivascular FAI measured around the left anterior descending artery (LAD) was higher in PIWH (-71.4±5.7 vs. -73.5±7.0; P=0.03) compared with that of the controls. The intra-group analyses of PIWH suggested that the decrease in nadir CD4+ T-cell count was associated with the increased prevalence of noncalcified plaque (OR, 4.139; 95% CI: 1.312-13.060; P=0.02). Conclusions: PIWH have a higher risk of developing noncalcified plaque and greater perivascular fat. In addition, the increased noncalcified plaque prevalence in PIWH may be associated with the immunodeficiency caused by HIV.

Optimization of genetic distance threshold for inferring the CRF01_AE molecular network based on next-generation sequencing.

Introduction: HIV molecular network based on genetic distance (GD) has been extensively utilized. However, the GD threshold for the non-B subtype differs from that of subtype B. This study aimed to optimize the GD threshold for inferring the CRF01_AE molecular network. Methods: Next-generation sequencing data of partial CRF01_AE pol sequences were obtained for 59 samples from 12 transmission pairs enrolled from a high-risk cohort during 2009 and 2014. The paired GD was calculated using the Tamura-Nei 93 model to infer a GD threshold range for HIV molecular networks. Results: 2,019 CRF01_AE pol sequences and information on recent HIV infection (RHI) from newly diagnosed individuals in Shenyang from 2016 to 2019 were collected to construct molecular networks to assess the ability of the inferred GD thresholds to predict recent transmission events. When HIV transmission occurs within a span of 1-4 years, the mean paired GD between the sequences of the donor and recipient within the same transmission pair were as follow: 0.008, 0.011, 0.013, and 0.023 substitutions/site. Using these four GD thresholds, it was found that 98.9%, 96.0%, 88.2%, and 40.4% of all randomly paired GD values from 12 transmission pairs were correctly identified as originating from the same transmission pairs. In the real world, as the GD threshold increased from 0.001 to 0.02 substitutions/site, the proportion of RHI within the molecular network gradually increased from 16.6% to 92.3%. Meanwhile, the proportion of links with RHI gradually decreased from 87.0% to 48.2%. The two curves intersected at a GD of 0.008 substitutions/site. Discussion: A suitable range of GD thresholds, 0.008-0.013 substitutions/site, was identified to infer the CRF01_AE molecular transmission network and identify HIV transmission events that occurred within the past three years. This finding provides valuable data for selecting an appropriate GD thresholds in constructing molecular networks for non-B subtypes.

Low-level viremia episodes appear to affect the provirus composition of the circulating cellular HIV reservoir during antiretroviral therapy.

Low-level viremia (LLV) ranging from 50 to 1,000 copies/ml is common in most HIV-1-infected patients receiving antiretroviral therapy (ART). However, the source of LLV and the impact of LLV on the HIV-1 reservoir during ART remain uncertain. We hypothesized that LLV may arise from the HIV reservoir and its occurrence affect the composition of the reservoir after LLV episodes. Accordingly, we investigated the genetic linkage of sequences obtained from plasma at LLV and pre-ART time points and from peripheral blood mononuclear cells (PBMCs) at pre-ART, pre-LLV, LLV, and post-LLV time points. We found that LLV sequences were populated with a predominant viral quasispecies that accounted for 67.29%∼100% of all sequences. Two episodes of LLV in subject 1, spaced 6 months apart, appeared to have originated from the stochastic reactivation of latently HIV-1-infected cells. Moreover, 3.77% of pre-ART plasma sequences were identical to 67.29% of LLV-3 plasma sequences in subject 1, suggesting that LLV may have arisen from a subset of cells that were infected before ART was initiated. No direct evidence of sequence linkage was found between LLV viruses and circulating cellular reservoirs in all subjects. The reservoir size, diversity, and divergence of the PBMC DNA did not differ significantly between the pre- and post-LLV sampling points (P > 0.05), but the composition of viral reservoir quasispecies shifted markedly before and after LLV episodes. Indeed, subjects with LLV had a higher total PBMC DNA level, greater viral diversity, a lower proportion of variants with identical sequences detected at two or more time points, and a shorter variant duration during ART compared with subjects without LLV. Overall, our findings suggested that LLV viruses may stem from an unidentified source other than circulating cellular reservoirs. LLV episodes may introduce great complexity into the HIV reservoir, which brings challenges to the development of treatment strategies.

Proppant Settlement and Long-Term Conductivity Calculation in Complex Fractures.

The current research on fracture conductivity ignores the placement of the proppant in fractures and relies on single-fracture conductivity testing and calculation, which cannot represent the overall conductivity of complex fracture systems. This research proposes a calculation method for the long-term conductivity of complex fractures based on proppant placement. This method considers fracture morphology, proppant placement, proppant embedment, and deformation under high closing pressure. The research results show that fracture conductivity decreases with increasing time, which can be divided into three stages: the embedding stage, the creep stage, and the stabilization stage. The long-term conductivity of the main fracture is higher than that of the branching fracture. With increasing closing pressure, the conductivities of both the main fracture and the branching fracture decrease. This is because increasing closure stress accelerates proppant embedment and creep, compressing the fluid flow space and further reducing fracture conductivity. Fracture conductivity is related to the placement of the proppant and sand concentration. Increasing the sand ratio can significantly increase the placement of the proppant in the main fracture and branching fractures, thereby improving fracture conductivity. Increasing the fracturing fluid viscosity can increase its proppant migration capacity. The proppant does not easily settle prematurely in high-viscosity fracturing fluid and can enter more into branching fractures, thereby improving their conductivity.

Network Pharmacology-Based Identification of Key Pharmacological Mechanism of Shen-qi-di-huang Decoction Acting on Uremia.

This study employs network pharmacology to uncover the pharmacological mechanisms underlying Shen-qi-di-huang decoction's efficacy in treating uremia. We identified a total of 927 differentially expressed genes (DEGs) through differential expression analysis and the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis platform, of which 607 were downregulated and 320 were upregulated. We also obtained the effective biological components and related target gene information of Chinese herbal medicines such as Renshen, Huangqi, shudihuang, Shanyao, Fuling, Mudanpi, and Shanzhuyu in Shen-qi-di-huang decoction and constructed a regulatory relationship network between molecular components and target genes in Shen-qi-di-huang decoction. We then constructed a protein-protein interaction (PPI) network of 15 targeted genes (RXRA, ND6, CYP1B1, SLPI, CDKN1A, RB1, HIF1A, MYC, HSPB1, IFNGR1, NQO1, IRF1, RASA1, PSMG1 and MAP2K4) using the STRING database and visualized the PPI network using the software Cytoscape. In addition, we revealed the key molecular functions of uremia through Gene Ontology (GO) enrichment analysis, mainly including neuron apoptotic process, cellular response to oxidative stress, regulation of neuron apoptotic process, neuron projection cytoplasm, RNA polymerase II transcription regulator complex, plasma membrane bounded cell projection cytoplasm, NADH and NADPH dehydrogenase (quinone) activity, protein kinase inhibitor and ubiquitin protein ligase binding, etc. Finally, we identified important biological pathways in uremia through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which mainly concentrated in Kaposi sarcoma-associated, small cell lung cancer, Gastric cancer, Hepatitis B and C, Hepatocellular carcinoma, Thyroid cancer, Bladder cancer, MAPK signaling pathway, ErbB signaling pathway, Th17 cell differentiation, HIF-1 signaling pathway, Thyroid hormone signaling pathway and Cell cycle, etc. Using integrated bioinformatical analysis, we elucidated key pharmacological mechanisms based on targeted genes, which was enable early identification of patients with uremia and would contribute to early clinical diagnosis and treatment of patients.

Direct Laser Writing Photonic Crystal Hydrogels with a Supramolecular Sacrificial Scaffold.

Photonic crystal hydrogels (PCHs), with smart stimulus-responsive abilities, have been widely exploited as colorimetric sensors for years. However, the current fabrication technologies are mostly applicable to produce PCHs with simple geometries at the sub-millimeter scale, limiting the introduction of structural design into PCH sensors as well as the accompanied advanced applications. This paper reports the microfabrication of three-dimensional (3D) PCHs with the help of supramolecular agarose PCH as a sacrificial scaffold by two-photon lithography (TPL). The supramolecular PCHs, formulated with SiO2 colloidal nanoparticles and agarose aqueous solutions, show bright structural color and are degradable upon short-time dimethyl sulfoxide treatment. Leveraging the supramolecular PCH as a sacrificial scaffold, PCHs with precise 3D geometries can be fabricated in an economical and efficient way. This work demonstrates the application of such a strategy in the creation of structural-designed PCH mechanical microsensors that have not been explored before.

Inhibitory receptor CD47 binding to plasma TSP1 suppresses NK-cell IFN-γ production via activating the JAK/STAT3 pathway during HIV infection.

BACKGROUND: Natural killer (NK) cells play an important first-line role against tumour and viral infections and are regulated by inhibitory receptor expression. Among these inhibitory receptors, the expression, function, and mechanism of cluster of differentiation 47 (CD47) on NK cells during human immunodeficiency virus (HIV) infection remain unclear. METHODS: Fresh peripheral blood mononuclear cells (PBMCs) were collected from people living with HIV (PLWH) and HIV negative controls (NC) subjects. Soluble ligand expression levels of CD47 were measured using ELISA. HIV viral proteins or Toll-like receptor 7/8 (TLR7/8) agonist was used to investigate the mechanisms underlying the upregulation of CD47 expression. The effect of CD47 on NK cell activation, proliferation, and function were evaluated by flow cytometry. RNA-seq was used to identify downstream pathways for CD47 and its ligand interactions. A small molecule inhibitor was used to restore the inhibition of NK cell function by CD47 signalling. RESULTS: CD47 expression was highly upregulated on the NK cells from PLWH, which could be due to activation of the Toll-like receptor 7/8 (TLR7/8) pathway. Compared with NC subjects, PLWH subjects exhibited elevated levels of CD47 ligands, thrombospondin-1 (TSP1), and counter ligand signal regulatory protein-α (SIRPα). The TSP1-CD47 axis drives the suppression of interferon gamma (IFN-γ) production and the activation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway in NK cells. After treatment with a STAT3 inhibitor, the NK cells from PLWH showed significantly improved IFN-γ production. CONCLUSIONS: The current data indicate that the binding of the inhibitory receptor CD47 to plasma TSP1 suppresses NK cell IFN-γ production by activating the JAK/STAT3 pathway during HIV infection. Our results suggest that CD47 and its related signalling pathways could be targets for improving NK cell function in people living with HIV.

Imaging cellular forces with photonic crystals.

Current techniques for visualizing and quantifying cellular forces have limitations in live cell imaging, throughput, and multi-scale analysis, which impede progress in cell force research and its practical applications. We developed a photonic crystal cellular force microscopy (PCCFM) to image vertical cell forces over a wide field of view (1.3 mm ⨯ 1.0 mm, a 10 ⨯ objective image) at high speed (about 20 frames per second) without references. The photonic crystal hydrogel substrate (PCS) converts micro-nano deformations into perceivable color changes, enabling in situ visualization and quantification of tiny vertical cell forces with high throughput. It enabled long-term, cross-scale monitoring from subcellular focal adhesions to tissue-level cell sheets and aggregates.

Effectiveness and safety of community-led assisted partner service among HIV-diagnosed men who have sex with men: a multicentre, randomized controlled trial in China.

Background: No randomized controlled trials have involved established HIV-diagnosed men who have sex with men (MSM) diagnosed for more than 6 months into the assisted partner service (aPS). We compared voluntary aPS involving community-based organizations (CBOs) and HIV self-testing (aPSST) with regular partner service (rPS) in HIV-diagnosed MSM irrespective of diagnosis time. Methods: In this unblinded, multicentre trial, we enrolled HIV-diagnosed MSM irrespective of diagnosis time in three cities in northern China. Index patients were randomly assigned to aPSST or rPS. Index patients in the aPSST group were additionally provided a comprehensive intervention package including HIV self-testing and CBO-based aPS compared with rPS group. The primary outcome was the number of index patients whose any sexual partner tested for HIV during the 6-month study. Completion of HIV testing was defined as sexual partners taking a clinic-based HIV test or HIV self-testing. Safety was assessed preliminary at the end of the 6-month follow-up. This study has been registered at chictr.org.cn (ChiCTR2000038784). Findings: From March to December 2021, 325 of HIV-diagnosed MSM were enrolled (90⋅2% were established HIV-diagnosed MSM) and randomly assigned to receive aPSST (n = 167) or rPS (n = 158). At 6 months, 110 (65⋅9%) index patients in the aPSST group had at least one sexual partner tested for HIV compared with 50 (31⋅6%) in the rPS group (hazard ratio 2⋅86; 95% confidence interval 2⋅03-4⋅03; p < 0⋅001). No significant difference was observed in effects of aPSST on HIV testing promotion between established and newly HIV-diagnosed MSM. Self-reported harms were infrequently observed in both groups (approximately 2⋅0%). Interpretation: Among HIV-diagnosed MSM regardless of diagnosis time, voluntary aPS involving CBOs and HIV self-testing was effective and safe for promoting partner HIV testing. Funding: This work was supported by the Mega-Projects of National Science Research, the National Natural Science Foundation of China and the Liaoning Revitalization Talents Program, China.

Co-occurrence of fecal incontinence with constipation or irritable bowel syndrome indicates the need for personalized treatment.

BACKGROUND: This study aimed to compare the prevalence and symptoms of fecal incontinence (FI) in relation to irritable bowel syndrome (IBS-associated FI), constipation (constipation-associated FI), and isolation (isolated FI). METHODS: Data were analyzed from 3145 respondents without organic comorbidities known to influence defecation function from the general Chinese population who filled in the online Groningen Defecation and Fecal Continence questionnaire. FI, IBS, and constipation were evaluated with the Rome IV criteria. KEY RESULTS: The prevalence of FI was 10.5% (n = 329) in the non-comorbidity group. After multivariable logistic regression analysis, IBS (odds ratio [OR]: 12.55, 95% confidence interval [CI]: 9.06-17.36) and constipation (OR: 4.38, 95% CI: 3.27-5.85) were the most significant factors contributing to FI. Based on this finding, 106/329 (32.2%) had IBS-associated FI, 119/329 (36.2%) had constipation-associated FI, and 104/329 (31.6%) had isolated FI. Among the 329 FI respondents, there was a high prevalence of IBS and constipation-related symptoms, including abdominal pain (81.5%) and abdominal bloating (77.8%) for IBS and straining during defecation (75.4%), incomplete defecation (72.3%), defecation blockage (63.2%), anal pain during defecation (59.3%), and hard stools (24%) for constipation. The patients with IBS-associated FI asked for specialists' help less frequently than those with isolated FI. Interestingly, among the patients with constipation-associated FI, 56.3% used anti-diarrhea medicine. CONCLUSIONS AND INFERENCES: The prevalence of IBS-associated FI, constipation-associated FI, and isolated FI is comparably high. It is important to diagnose and target the cause of FI to provide personalized and cause-targeting care instead of treating only the FI symptoms.

Validation of the Chinese DeFeC questionnaire: a comprehensive screening tool for symptoms and causes of constipation and incontinence.

BACKGROUND: Currently, the diagnosis of defecation disorders in China is usually based on varied and ambiguous criteria. We aimed to translate the Groningen Defecation and Fecal Continence (DeFeC) questionnaire to Chinese and test its reproducibility and feasibility in the general Chinese population. METHODS: The Groningen Defecation Questionnaire was translated into Chinese according to the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN). The feasibility and reproducibility were evaluated by performing a test-retest online survey and calculating the Cohen's kappa (κ) coefficient [or intraclass correlation coefficient (ICC)], with 0.01-0.20 considered slight agreement; 0.21-0.40, fair agreement; 0.41-0.60, moderate agreement; 0.61-0.80, substantial agreement; and 0.81-1.00, almost perfect agreement. RESULTS: In total, 130 respondents completed the questionnaire twice, with a mean age of 47.08±12.46 years. No remarks were made that indicted that the questions were difficult to understand. The median time to complete the questionnaire was 20.78 min [interquartile range (IQR), 14.83-29.20 min] for the first time. The κ coefficient of all defecation function-related domains ranged between 0.25 and 0.71, with an average value of 0.53. The constipation and fecal incontinence-related domains showed a substantial and moderate agreement level, as indicated by κ of 0.65 and 0.52, respectively. The Agachan constipation score and Wexner incontinence score showed perfect and substantial agreement, as indicated by an ICC of 0.88 and 0.74, respectively. CONCLUSIONS: The Chinese version of the Groningen DeFeC questionnaire is highly feasible and reproducible and can be applied in clinical and research activities for the Chinese population.

Cardiac MRI-Based Assessment of Myocardial Injury in Asymptomatic People Living With Human Immunodeficiency Virus: Correlation With nadir CD4 Count.

BACKGROUND: There are known cardiac manifestations of HIV, but the findings in asymptomatic subjects are still not fully explored. PURPOSE: To evaluate for the presence of subclinical myocardial injury in asymptomatic people living with human immunodeficiency virus (PLWH) by cardiac MRI and to explore the possible association between subclinical myocardial injury and HIV-related clinical characteristics. STUDY TYPE: Cross-sectional. POPULATION: A total of 80 asymptomatic PLWH (age: 53 years [47-56 years]; 90% male) and 50 age- and sex-matched healthy participants. FIELD STRENGTH/SEQUENCE: A 3-T, cine sequence, T1, T2, and T2* mapping. ASSESSMENT: Function analysis was derived from short axis, two-, three-, and four-chamber cine images by feature tracking. Regions of interest were manually selected in the midventricular septum T1, T2, and T2* mapping sequences. PLWH were evaluated for T1 increment (△T1 mapping = native T1 - cutoff values) and HIV-related clinical characteristics, particularly the nadir CD4 count. And PLWH were stratified into two groups according to the cutoff value of native T1: elevated native T1 and normal. STATISTICAL TESTS: T test, Wilcoxon rank-sum test, Chi-square test, Spearman rank correlation, and logistic regression. P <0.05 indicated statistical significance. RESULTS: Asymptomatic PLWH revealed significantly higher native myocardial T1 values (1241 ± 29 msec vs. 1189 ± 21 msec), T2 values (40.7 ± 1.5 msec vs. 37.9 ± 1.4 msec), and lower LVGRS (30.2% ± 6.2% vs. 35.8% ± 6.4%), LVGCS (-18.0% ± 2.5% vs. -19.5% ± 2.0%), and LVGLS (-16.0% ± 3.8% vs. -17.9% ± 2.6%) but showed no difference in T2* values (17.3 msec [16.3-19.1 msec] vs. 18.3 msec [16.5-19.3 msec], P = 0.201). A negative correlation between the native T1 increment in PLWH with subclinical myocardial injury and the nadir CD4 count (u = -0.316). Nadir CD4 count <500 cells/mm3 was associated with higher odds of elevated native T1 myocardial values (odds ratio, 6.12 [95% CI, 1.07-34.91]) in PLWH. DATA CONCLUSION: Subclinical myocardial inflammation and dysfunction were present in asymptomatic PLWH, and a lower nadir CD4 count may be a risk factor for subclinical myocardial injury. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

Altered lipid metabolites accelerate early dysfunction of T cells in HIV-infected rapid progressors by impairing mitochondrial function.

The complex mechanism of immune-system damage in HIV infection is incompletely understood. HIV-infected "rapid progressors" (RPs) have severe damage to the immune system early in HIV infection, which provides a "magnified" opportunity to study the interaction between HIV and the immune system. In this study, forty-four early HIV-infected patients (documented HIV acquisition within the previous 6 months) were enrolled. By study the plasma of 23 RPs (CD4+ T-cell count < 350 cells/µl within 1 year of infection) and 21 "normal progressors" (NPs; CD4+ T-cell count > 500 cells/µl after 1 year of infection), eleven lipid metabolites were identified that could distinguish most of the RPs from NPs using an unsupervised clustering method. Among them, the long chain fatty acid eicosenoate significantly inhibited the proliferation and secretion of cytokines and induced TIM-3 expression in CD4+ and CD8+ T cells. Eicosenoate also increased levels of reactive oxygen species (ROS) and decreased oxygen consumption rate (OCR) and mitochondrial mass in T cells, indicating impairment in mitochondrial function. In addition, we found that eicosenoate induced p53 expression in T cells, and inhibition of p53 effectively decreased mitochondrial ROS in T cells. More importantly, treatment of T cells with the mitochondrial-targeting antioxidant mito-TEMPO restored eicosenoate-induced T-cell functional impairment. These data suggest that the lipid metabolite eicosenoate inhibits immune T-cell function by increasing mitochondrial ROS by inducing p53 transcription. Our results provide a new mechanism of metabolite regulation of effector T-cell function and provides a potential therapeutic target for restoring T-cell function during HIV infection.

Molecular Network Analysis Discloses the Limited Contribution to HIV Transmission for Patients with Late HIV Diagnosis in Northeast China.

In the "treat all" era, the high rate of late HIV diagnosis (LHD) worldwide remains an impediment to ending the HIV epidemic. In this study, we analyzed LHD in newly diagnosed people living with HIV (PLWH) and its impact on HIV transmission in Northeast China. Sociodemographic information, baseline clinical data, and plasma samples obtained from all newly diagnosed PLWH in Shenyang, the largest city in Northeast China, between 2016 and 2019 were evaluated. Multivariate logistic regression analysis was performed to identify risk factors associated with LHD. A molecular network based on the HIV pol gene was constructed to assess the risk of HIV transmission with LHD. A total of 2882 PLWH, including 882 (30.6%) patients with LHD and 1390 (48.2%) patients with non-LHD, were enrolled. The risk factors for LHD were older age (≥ 30 years: p < .01) and diagnosis in the general population through physical examination (p < .0001). Moreover, the molecular network analysis revealed that the clustering rate (p < .0001), the fraction of individuals with ≥ 4 links (p = .0847), and the fraction of individuals linked to recent HIV infection (p < .0001) for LHD were significantly or marginally significantly lower than those recorded for non-LHD. Our study indicates the major risk factors associated with LHD in Shenyang and their limited contribution to HIV transmission, revealing that the peak of HIV transmission of LHD at diagnosis may have been missed. Early detection, diagnosis, and timely intervention for LHD may prevent HIV transmission.

Begonia-Inspired Slow Photon Effect of a Photonic Crystal for Augmenting Algae Photosynthesis.

Plant photosynthesis is considered to be an environmentally friendly and effective measure for reducing carbon dioxide levels to meet the global objective of carbon neutrality. However, the light energy utilization of photosynthetic pigments is insufficient. Begonia pavonine (B. pavonina) with blue leaves exhibits a photosynthetic quantum yield 10% higher than those of other plants by virtue of their photonic crystal (PC) thylakoids. Inspired by this property, we prepared non-angle-dependent PC hydrogels and assembled them with algae Chlorella pyrenoidosa (C. pyre). The band edge of PC hydrogels matched the absorption peaks of C. pyre, and the resulting slow photon effect increased the interaction time between incident light and photosynthetic pigments, which in turn induced the expression of light-harvesting proteins and the synthesis of pigments, thereby improving the light energy utilization. Further, we introduced an artificial antenna into the assembly, which assisted the slow photon effect in increasing the oxygen evolution and carbon sequestration rate by more than 200%. This method avoids the photobleaching problems faced by methods of synthesizing artificial antenna pigments and the biosafety problems faced by genetically engineered methods of editing pigments or proteins.