Advances in Mechanism of HIV-1 Immune Reconstitution Failure: Understanding Lymphocyte Subpopulations and Interventions for Immunological Nonresponders.

In individuals diagnosed with AIDS, the primary method of sustained suppression of HIV-1 replication is antiretroviral therapy, which systematically increases CD4+ T cell levels and restores immune function. However, there is still a subset of 10-40% of people living with HIV who not only fail to reach normal CD4+ T cell counts but also experience severe immune dysfunction. These individuals are referred to as immunological nonresponders (INRs). INRs have a higher susceptibility to opportunistic infections and non-AIDS-related illnesses, resulting in increased morbidity and mortality rates. Therefore, it is crucial to gain new insights into the primary mechanisms of immune reconstitution failure to enable early and effective treatment for individuals at risk. This review provides an overview of the dynamics of key lymphocyte subpopulations, the main molecular mechanisms of INRs, clinical diagnosis, and intervention strategies during immune reconstitution failure, primarily from a multiomics perspective.

Neural predictors of fear depend on the situation.

The extent to which neural representations of fear experience depend on or generalize across the situational context has remained unclear. We systematically manipulated variation within and across three distinct fear-evocative situations including fear of heights, spiders, and social threats. Participants (n=21, 10 females and 11 males) viewed ∼20 second clips depicting spiders, heights, or social encounters, and rated fear after each video. Searchlight multivoxel pattern analysis (MVPA) was used to identify whether and which brain regions carry information that predicts fear experience, and the degree to which the fear-predictive neural codes in these areas depend upon or generalize across the situations. The overwhelming majority of brain regions carrying information about fear did so in a situation dependent manner. These findings suggest that local neural representations of fear experience are unlikely to involve a singular pattern, but rather a collection of multiple heterogeneous brain states.Significance Statement Much of the debate on the nature of emotion concerns the uniformity or heterogeneity of representation for particular emotion categories. Here we provide evidence that widely distributed activation patterns characteristic of recent neural signatures of fear reflect an amalgam of functionally heterogeneous brain states. Participants completed a novel fMRI task that parametrically examined subjective fear within and across three content-rich and naturalistic situations: fear of heights, spiders, and social threats. Using searchlight analysis and machine learning methods, we show that the overwhelming majority of brain regions that predict fear only do so for certain situations. These findings carry implications for the generalization of findings on fear across species, translational models of fear and anxiety, and developing neural signatures of fear.

Memory consolidation of sequence learning and dynamic adaptation during wakefulness.

Motor learning involves acquiring new movement sequences and adapting motor commands to novel conditions. Labile motor memories, acquired through sequence learning and dynamic adaptation, undergo a consolidation process during wakefulness after initial training. This process stabilizes the new memories, leading to long-term memory formation. However, it remains unclear if the consolidation processes underlying sequence learning and dynamic adaptation are independent and if distinct neural regions underpin memory consolidation associated with sequence learning and dynamic adaptation. Here, we first demonstrated that the initially labile memories formed during sequence learning and dynamic adaptation were stabilized against interference through time-dependent consolidation processes occurring during wakefulness. Furthermore, we found that sequence learning memory was not disrupted when immediately followed by dynamic adaptation and vice versa, indicating distinct mechanisms for sequence learning and dynamic adaptation consolidation. Finally, by applying patterned transcranial magnetic stimulation to selectively disrupt the activity in the primary motor (M1) or sensory (S1) cortices immediately after sequence learning or dynamic adaptation, we found that sequence learning consolidation depended on M1 but not S1, while dynamic adaptation consolidation relied on S1 but not M1. For the first time in a single experimental framework, this study revealed distinct neural underpinnings for sequence learning and dynamic adaptation consolidation during wakefulness, with significant implications for motor skill enhancement and rehabilitation.

Population Balance Equations for Reactive Separation in Polymer Upcycling.

Many polymer upcycling efforts aim to convert plastic waste into high-value liquid hydrocarbons. However, the subsequent cleavage of middle distillates to light gases can be problematic. The reactor often contains a vapor phase (light gases and middle distillates) and a liquid phase (molten polymers and waxes with a suspended or dissolved catalyst). Because the catalyst resides in the liquid phase, middle distillates that partition into the vapor phase are protected against further cleavage into light gases. In this paper, we consider a simple reactive separation strategy, in which a gas outflow removes the volatile products as they form. We combine vapor-liquid equilibrium models and population balance equations (PBEs) to describe polymer upcycling in a two-phase semibatch reactor. The results suggest that the temperature, headspace volume, and flow rate of the reactor can be used to tune selectivity toward the middle distillates, in addition to the molecular mechanism of catalysis. We anticipate that two-phase reactor models will be important in many polymer upcycling processes and that reactive separation strategies will provide ways to boost the yield of the desired products in these cases.

Alterations of the microbiome across body sites in systemic lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with unclear etiology. Growing evidence suggests the microbiome plays a role in SLE pathogenesis. However, findings are inconsistent across studies due to factors like small sample sizes and geographical variations. A comprehensive meta-analysis is needed to elucidate microbiome alterations in SLE. OBJECTIVE: This study aimed to provide a systematic overview of microbiota dysbiosis across body sites in SLE through a meta-analysis of alpha diversity indices, beta diversity indices, and abundance taxa of microbiome. METHODS: A literature search was conducted across four databases to identify relevant studies comparing SLE patients and healthy controls. Extracted data encompassed alpha and beta diversity metrics, as well as bacterial, fungal, and viral abundance across gut, oral, skin, and other microbiota. Study quality was assessed using the Newcastle-Ottawa Scale. Standardized mean differences and pooled effect sizes were calculated through meta-analytical methods. RESULTS: The analysis showed reduced alpha diversity and distinct beta diversity in SLE, particularly in the gut microbiota. Taxonomic analysis revealed compositional variations in bacteria from the gut and oral cavity. However, results for fungi, viruses, and bacteria from other sites were inconsistent due to limited studies. CONCLUSIONS: This meta-analysis offers a comprehensive perspective on microbiome dysbiosis in SLE patients across diverse body sites and taxa. The observed variations underscore the microbiome's potential role in SLE pathogenesis. Future research should address geographical variations, employ longitudinal designs, and integrate multi-omics approaches.

Comprehensive evaluation of the efficacy and safety of a new multi-component anti-aging topical eye cream.

BACKGROUND: The delicate periorbital region is susceptible to skin dehydration, wrinkles, and loss of elasticity. Thus, targeted and effective anti-aging interventions are necessary for the periorbital area. AIM: To evaluate the efficacy and safety of a new anti-aging eye cream formulated with the active complex (Yeast/rice fermentation filtrate, N-acetylneuraminic acid, palmityl tripeptide-1, and palmitoyl tetrapeptide-7). METHODS: The cell viability and expressions of key extracellular matrix (ECM) components of the active complex were evaluated using a human skin fibroblast model. In the 12-week clinical trial, skin hydration, elasticity, facial photographs, and collagen density following eye cream application were assessed using Corneometer, Cutometer, VISIA, and ultrasound device, respectively. Dermatologists and participants evaluated clinical efficacy and safety at baseline, and after 4, 8, and 12 weeks. RESULTS: PCR and immunofluorescent analyses revealed that the active complex significantly stimulated fibroblast proliferation (p < 0.05) and markedly promote the synthesis of collagen and elastin. Clinical findings exhibited a substantial enhancement in skin hydration (28.12%), elasticity (18.81%), and collagen production (54.99%) following 12 weeks of eye cream application. Dermatological evaluations and participants' assessments reported a significant improvement in skin moisture, roughness, elasticity, as well as fine lines and wrinkles by week 8. CONCLUSION: The new anti-aging eye cream, enriched with the active complex, demonstrates comprehensive rejuvenating effects, effectively addressing aging concerns in the periorbital area, coupled with a high safety profile.

Environmental triggers of autoimmunity: The association between bisphenol analogues and systemic lupus erythematosus.

The aim of this research was to examine the correlation between the exposure to bisphenol analogues (BPs), such as bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS), and the risk of developing systemic lupus erythematosus (SLE). Ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was utilized to measure the levels of BPA, BPF, and BPS in the urine of 168 female participants diagnosed with SLE and 175 female participants who were deemed healthy controls. Logistic regression models were utilized to assess the connections between levels of bisphenol and the risk of SLE. The findings indicated that levels of BPA and BPF in the urine of individuals with SLE were markedly elevated compared to those in the control group. Higher exposure to BPA and BPF exhibited positive dose-response relationships with increased SLE risk. No significant associations were identified between BPS and the risk of SLE. These findings suggest exposure to BPA and BPF may be implicated as novel environmental triggers in the development of autoimmunity such as SLE. The significantly increased levels of these bisphenol analogues detected in SLE patients versus healthy controls, along with the associations between higher exposures and elevated SLE risk, which offers crucial hints for comprehending how endocrine-disrupting substances contribute to the genesis of autoimmune illnesses. Further research using robust longitudinal assessments of bisphenol analogue exposures is warranted to corroborate these epidemiological findings. Overall, this study highlights potential environmental risk factors for SLE while calling for additional investigation into the impact of bisphenol exposures on autoimmunity development.

A combination technique of strip free gingival grafts and xenogeneic collagen matrix in augmenting keratinized mucosa around dental implants: a single-arm clinical trial.

BACKGROUND: The aim of this study was to assess the outcomes of the combination technique of strip free gingival grafts (SFGG) and xenogeneic collagen matrix (XCM) in augmenting the width of keratinized mucosa (KMW) around dental implants, and compare its efficacy with the historical control group (FGG). METHODS: Thirteen patients with at least one site with KMW ≤ 2 mm after implant surgery were included and received SFGG in combination with XCM. Another thirteen patients with the same inclusion and exclusion criteria from the previous trial received FGG alone. The same outcomes as the previous trial were evaluated. KMW, thickness of keratinized mucosa (KMT), gingival index (GI) and probing depth (PD) were measured at baseline, 2 and 6 months. Postoperative pain, patient satisfaction and aesthetic outcomes were also assessed. RESULTS: At 6 months after surgery, the combination technique could attain 3.3 ± 1.6 mm of KMW. No significant change could be detected in GI or PD at 6 months compared to those at 2 months (p > 0.05). The postoperative pain and patient satisfaction in VAS were 2.6 ± 1.2 and 9.5 ± 1.2. The total score of aesthetic outcomes was 3.8 ± 1.2. In the historical FGG group, 4.6 ± 1.6 mm of KMW was reported at 6 months, and the total score of aesthetic outcomes was higher than the combination technique (4.8 ± 0.7 vs. 3.8 ± 1.2, p < 0.05). CONCLUSIONS: The combination technique of SFGG and XCM could increase KMW and maintain peri-implant health. However, this combination technique was associated with inferior augmentation and aesthetic outcomes compared with FGG alone. TRIAL REGISTRATION: This clinical trial was registered in the Chinese Clinical Trial Registry with registration number ChiCTR2200057670 on 15/03/2022.

Zirconium-Catalyzed C-H Alumination of Polyolefins, Paraffins, and Methane.

C-H/Et-Al exchange in zirconium-catalyzed reactions of saturated hydrocarbons and AlEt3 affords versatile organoaluminum compounds and ethane. The grafting of commercially available Zr(OtBu)4 on silica/alumina gives monopodal ≡SiO-Zr(OtBu)3 surface pre-catalyst sites that are activated in situ by ligand exchange with AlEt3. The catalytic C-H alumination of dodecane at 150 °C followed by quenching in air affords n-dodecanol as the major product, revealing selectivity for methyl group activation. Shorter hydrocarbon or alcohol products were not detected under these conditions. Catalytic reactions of cyclooctane and AlEt3, however, afford ring-opened products, indicating that C-C bond cleavage occurs readily in methyl group-free reactants. This selectivity for methyl group alumination enables the C-H alumination of polyethylenes, polypropylene, polystyrene, and poly-α-olefin oils without significant chain deconstruction. In addition, the smallest hydrocarbon, methane, undergoes selective mono-alumination under solvent-free catalytic conditions, providing a direct route to Al-Me species.

Endocrine-disrupting chemicals and autoimmune diseases.

Endocrine-disrupting chemicals (EDCs) widely exist in people's production and life which have great potential to damage human and animal health. Over the past few decades, growing attention has been paid to the impact of EDCs on human health, as well as immune system. So far, researchers have proved that EDCs (such as bisphenol A (BPA), phthalate, tetrachlorodibenzodioxin (TCDD), etc.) affect human immune function and promotes the occurrence and development of autoimmune diseases (ADs). Therefore, in order to better understand how EDCs affect ADs, we summarized the current knowledge about the impact of EDCs on ADs, and elaborated the potential mechanism of the impact of EDCs on ADs in this review.

Electrospun Nanofibrous Conduit Filled with a Collagen-Based Matrix (ColM) for Nerve Regeneration.

Traumatic nerve defects result in dysfunctions of sensory and motor nerves and are usually accompanied by pain. Nerve guidance conduits (NGCs) are widely applied to bridge large-gap nerve defects. However, few NGCs can truly replace autologous nerve grafts to achieve comprehensive neural regeneration and function recovery. Herein, a three-dimensional (3D) sponge-filled nanofibrous NGC (sf@NGC) resembling the structure of native peripheral nerves was developed. The conduit was fabricated by electrospinning a poly(L-lactide-co-glycolide) (PLGA) membrane, whereas the intraluminal filler was obtained by freeze-drying a collagen-based matrix (ColM) resembling the extracellular matrix. The effects of the electrospinning process and of the composition of ColM on the physicochemical performance of sf@NGC were investigated in detail. Furthermore, the biocompatibility of the PLGA sheath and ColM were evaluated. The continuous and homogeneous PLGA nanofiber membrane had high porosity and tensile strength. ColM was shown to exhibit an ECM-like architecture characterized by a multistage pore structure and a high porosity level of over 70%. The PLGA sheath and ColM were shown to possess stagewise degradability and good biocompatibility. In conclusion, sf@NGC may have a favorable potential for the treatment of nerve reconstruction.

The effect of inherent and incidental constraints on bimanual and social coordination.

The current investigation was designed to examine the influence of inherent and incidental constraints on the stability characteristics associated with bimanual and social coordination. Individual participants (N = 9) and pairs of participants (N = 18, 9 pairs) were required to rhythmically coordinate patterns of isometric forces in 1:1 in-phase and 1:2 multi-frequency patterns by exerting force with their right and left limbs. Lissajous information was provided to guide performance. Participants performed 13 practice trials and 1 test trial per pattern. On the test trial, muscle activity from the triceps brachii muscles of each arm was recorded. EMG-EMG coherence between the two EMG signals was calculated using wavelet coherence. The behavioral data indicated that individual participants performed the 1:1 in-phase pattern more accurately and with less variability than paired participants. The EMG coherence analysis indicated significantly higher coherence for individual participants than for the paired participants during the 1:1 in-phase pattern, whereas no differences were observed between groups for the 1:2 coordination pattern. The results of the current investigation support the notion that neural crosstalk can stabilize 1:1 in-phase coordination when contralateral and ipsilateral signals are integrated via the neuromuscular linkage between two effectors.

KDM1A Identified as a Potential Oncogenic Driver and Prognostic Biomarker via Multi-Omics Analysis.

BACKGROUND: Lysine-specific demethylase 1A (KDM1A) is a histone demethylation enzyme and a crucial epigenetic factor for multiple pathological pathways that mediate carcinogenesis and immunogenicity. Although increasing evidence supposes the association between KDM1A and cancers, no systematic multi-omics analysis of KDM1A is available. METHODS: We systematically evaluated the KDM1A expression of various cancer and normal tissues and the unique relationship between KDM1A expression and prognosis of cancer cases based on The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The genetic variations, phosphorylation, and DNA methylation of KDM1A were analyzed via various tools. We further analyzed the correlation of KDM1A expression and fibroblasts and immune cell infiltration score of TCGA samples via TIMER2.0. RESULTS: KDM1A was highly expressed in 17 types of total 33 cancers, while it expressed low levels in only 4 cancers. High KDM1A expression was associated with worse survival status in various cancers. KDM1A expression was positively correlated with the cancer-associated fibroblasts and myeloid-derived suppressor cells infiltration levels in most cancer types. Additionally, KDM1A in most cancer types was negatively correlated with Th1 cell infiltration and positively correlated with Th2 cells. Moreover, spliceosome, cell cycle, and RNA transport pathways were involved in the functional mechanisms of KDM1A via enrichment analysis. CONCLUSIONS: Our study describes the epigenetic factor KDM1A as an oncogene and prognostic biomarker. Our findings provide valuable guidance for further analysis of KDM1A function in pathogenesis and potential clinical treatment.

Accessing interpersonal and intrapersonal coordination dynamics.

Both intrapersonal and interpersonal coordination dynamics have traditionally been investigated using relative phase patterns of in-phase (ϕ = 0°) and/or anti-phase (ϕ = 180°). Numerous investigations have demonstrated that coordination tasks that require other relative phase patterns (e.g., 90°) are difficult or near impossible to perform without extended practice. Recent findings, however, have demonstrated that an individual can produce a wide range of intrapersonal bimanual patterns within a few minutes of practice when provided integrated feedback. The present experiment was designed to directly compare intra- and interpersonal coordination performance and variability when provided Lissajous feedback or pacing metronome. Single participants (N = 12) and pairs of participants (N = 24, 12 pairs) were required to produce relative phase patterns between 0° and 180° in 30° increments using either pacing metronomes or Lissajous displays. The Lissajous displays involved a goal template and a cursor providing integrated feedback regarding the position of the two effectors. The results indicated both single and pairs of participants could effectively produce a large range of coordination patterns that typically act as repellers after only 6 min of practice when provided integrated feedback. However, single participants performed the in-phase coordination pattern more accurately and with less variability than paired participants, regardless of the feedback condition. These results suggest an advantage for intrapersonal coordination when performing in-phase coordination, possibly due to the stabilizing effect occurring via the neuro-muscular linkage between effectors.

Indocyanine Green Loaded Modified Mesoporous Silica Nanoparticles as an Effective Photothermal Nanoplatform.

Photothermal therapy possesses great advantages for the treatment of drug-resistant tumors. Herein, Near Infrared (NIR)-triggered photothermal nanoparticles were developed through loading indocyanine green (ICG), a kind of NIR dye, into amino group-modified silica nanoparticles (SiO2-NH2 NPs). SiO2-NH2 NPs were prepared with immobilization of the amino groups into the framework of silica nanoparticles (SiO2 NPs) by employing (3-aminopropyl)-triethoxysilane (APTES). Before and after the modification of the amino group, the particle sizes of SiO2 NPs showed similar value, around 100 nm. ICG was further adsorbed into SiO2-NH2 NPs by electrostatic attraction to enable SiO2-NH2@ICG NPs as a kind of photothermal agent. The loading rate of ICG to SiO2-NH2 was greatly increased compared to unmodified SiO2, and the stability of ICG was also improved. Moreover, the SiO2-NH2@ICG NPs exhibited efficient photothermal effects due to ICG transforming laser power into local heat through the connected ICG, when NIR laser irradiation turned on for a couple of minutes. Finally, the in vitro antitumor efficacy of SiO2-NH2@ICG NPs was investigated by recording cell proliferation rate and further chronicled the apoptotic morphology evidence by a Calcein-AM/PI fluorescent staining assay, indicating the efficient photothermal targeted therapy for the HepG2 tumor cells.

Performance and microbial community variations of a upflow anaerobic sludge blanket (UASB) reactor for treating monosodium glutamate wastewater: Effects of organic loading rate.

To investigate the effect of the organic loading rate (OLR) on anaerobic treatment of monosodium glutamate (MSG) wastewater, a lab-scale up-flow anaerobic blanket (UASB) reactor was continuously operated over a 222-day period. The overall performances of COD removal and methane recovery initially exhibited an increase and subsequently decreased when the OLR was increased from 1 g-COD/L/d to 24 g-COD/L/d. At the optimal OLR of 8 g-COD/L/d, superior performance was obtained with a maximum COD removal efficiency of 97%, a methane production rate of 2.3 L/L/d, and specific methanogenic activity of 86 mg-CH4/g-VSS/d (feeding on glutamate), with superior characteristics of sludge in VSS concentration, average diameter of granules, and settling velocity. According to the results of the specific methanogenic activity, the methanogenic pathway was more inclined to pass through acetate than through hydrogen. Methanosarcina instead of Methanosaeta, with Methanobacterium and greatly increased Firmicutes, dominated in the UASB reactor after long term operation. These results support that the OLR had a substantial effect on both the treatment and energy recovery efficiency of MSG wastewater as well as on microbial community variations in the UASB reactor.

Core-shell structured magnetic mesoporous carbon nanospheres derived from metal-polyphenol coordination polymer-coated Fe3 O4 and its application in the enrichment of phthalates from water samples.

In this work, core-shell structured magnetic mesoporous carbon nanospheres were fabricated from the carbonization of metal-polyphenol coordination polymer-coated Fe3 O4 nanoparticles. The preparation method is simple, fast, versatile, and easy to scale up. Magnetic mesoporous carbon nanospheres exhibit a high specific surface area, high superparamagnetism, and high adsorption efficiencies for phthalates. Four phthalates were extracted from aqueous solutions by using magnetic mesoporous carbon nanospheres via magnetic solid phase extraction. Subsequent analysis was performed by using high-performance liquid chromatography with ultraviolet detection. The analytical method has good linearity in the concentration range of 1-200 ng/mL for diethyl phthalate, diisobutyl phthalate, and dicyclohexyl phthalate, and 3-200 ng/mL for dipropyl phthalate. The limits of detection were in the range of 0.10-0.62 ng/mL. Compared with previous methods, this method has a lower detection limit, wider linearity range, and faster adsorption and desorption rates. The results indicate that magnetic mesoporous carbon nanospheres are suitable for the enrichment of hydrophobic substances from aqueous solutions.

Wet flue gas desulfurization wastewater treatment with reclaimed water treatment plant sludge: a case study.

To upgrade a wet flue gas desulfurization (FGD) wastewater treatment process in a typical thermal power plant (TPP) in Hunan province, China, a new concept for reusing polyaluminum chloride (PAC)-based water treatment plant sludge (WTPS) as a coagulant is proposed. Results show that, for an optimal WTPS dosage of 1,000 mg/L, the corresponding removal capacities for suspended solids (SS) and chemical oxygen demand (COD) from the practical FGD wastewater were 58.3% and 40.3%, respectively. Through an advanced treatment with a dosage of 50 mg/L of PAC, pH of 9, and stirring of 150 r/min for 60 s and 50 r/min for 15 min, the total removal efficiencies of SS, COD, and total cadmium (Cd) from the FGD wastewater were 93.7%, 88.8%, and 84.6%, respectively. Therefore, a new modification process (that involves mixing with WTPS - slag cleaner - neutralization - coagulation - sedimentation) was proposed. The proposed process is economically superior, and the average cost for the FGD wastewater treatment was only 1.08 USD/t. This could provide a cost-effective alternative process for upgrading FGD wastewater treatment facilities of TPPs.

Overexpression of SphK1 enhances cell proliferation and invasion in triple-negative breast cancer via the PI3K/AKT signaling pathway.

Sphingosine kinase 1 (SphK1) expression is elevated in various cancers and is associated with shorter survival times for patients. However, the molecular mechanism of SphK1 up-regulation in triple-negative breast cancer (TNBC) remains unclear. In this study, we assayed the expression level of SphK1 in TNBC tissues by qRT-PCR and immunohistochemistry. The level of S1P was quantified by ELISA in the serum of TNBC patients. Our results found that the levels of SphK1 and S1P were significantly increased in TNBC patients compared with normal control. Furthermore, knockdown of SphK1 with siRNA decreased TNBC cell proliferation and inhibited cell migration/invasion. These data suggest that SphK1 has an important role in TNBC and presents an attractive therapeutic target for the treatment for TNBC.