Prospective and multi-reader evaluation of deep learning reconstruction-based accelerated rectal MRI: image quality, diagnostic performance, and reading time.

OBJECTIVES: To evaluate deep learning reconstruction (DLR)-based accelerated rectal magnetic resonance imaging (MRI) compared with standard MRI. MATERIALS AND METHODS: Patients with biopsy-confirmed rectal adenocarcinoma between November/2022 and May/2023 in a single centre were prospectively enrolled for an intra-individual comparison between standard fast spin-echo (FSEstandard) and DLR-based FSE (FSEDL) sequences. Quantitative and qualitative image quality metrics of the pre-therapeutic MRIs were evaluated in all patients; diagnostic performance and evaluating time for T-staging, N-staging, extramural vascular invasion (EMVI), and mesorectal fascia (MRF) status was further analysed in patients undergoing curative surgery, with histopathologic results as the diagnostic gold standard. RESULTS: A total of 117 patients were enrolled, with 60 patients undergoing curative surgery. FSEDL reduced the acquisition time by 65% than FSEstandard. FSEDL exhibited higher signal-to-noise ratios, contrast-to-noise ratio, and subjective scores (noise, tumour margin clarity, visualisation of bowel wall layering and MRF, overall image quality, and diagnostic confidence) than FSEstandard (p < 0.001). Reduced artefacts were observed in FSEDL for patients without spasmolytics (p < 0.05). FSEDL provided higher T-staging accuracy by junior readers than FSEstandard (reader 1, 58.33% vs 70.00%, p = 0.016; reader 3, 60.00% vs 76.67%, p = 0.021), with similar N-staging, EMVI, and MRF performance. No significant difference was observed for senior readers. FSEDL exhibited shorter diagnostic time in all readers' T-staging and overall evaluation, and junior readers' EMVI and MRF (p < 0.05). CONCLUSION: FSEDL provided improved image quality, reading time, and junior radiologists' T-staging accuracy than FSEstandard, while reducing the acquisition time by 65%. CLINICAL RELEVANCE STATEMENT: DLR is clinically applicable for rectal MRI, providing improved image quality with shorter scanning time, which may ease the examination burden. It is beneficial for diagnostic optimisation in improving junior radiologists' T-staging accuracy and reading time. KEY POINTS: The rising incidence of rectal cancer has demanded enhanced efficiency and quality in imaging examinations. FSEDL demonstrated superior image quality and had a 65% reduced acquisition time. FSEDL can improve the diagnostic accuracy of T-staging and reduce the reading time for assessing rectal cancer.

Another Year of Record Heat for the Oceans.

Changes in ocean heat content (OHC), salinity, and stratification provide critical indicators for changes in Earth's energy and water cycles. These cycles have been profoundly altered due to the emission of greenhouse gasses and other anthropogenic substances by human activities, driving pervasive changes in Earth's climate system. In 2022, the world's oceans, as given by OHC, were again the hottest in the historical record and exceeded the previous 2021 record maximum. According to IAP/CAS data, the 0-2000 m OHC in 2022 exceeded that of 2021 by 10.9 ± 8.3 ZJ (1 Zetta Joules = 1021 Joules); and according to NCEI/NOAA data, by 9.1 ± 8.7 ZJ. Among seven regions, four basins (the North Pacific, North Atlantic, the Mediterranean Sea, and southern oceans) recorded their highest OHC since the 1950s. The salinity-contrast index, a quantification of the "salty gets saltier-fresh gets fresher" pattern, also reached its highest level on record in 2022, implying continued amplification of the global hydrological cycle. Regional OHC and salinity changes in 2022 were dominated by a strong La Niña event. Global upper-ocean stratification continued its increasing trend and was among the top seven in 2022.

Triamcinolone acetonide-loaded nanoparticles encapsulated by CD90+ MCSs-derived microvesicles drive anti-inflammatory properties and promote cartilage regeneration after osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a highly prevalent human degenerative joint disorder that has long plagued patients. Glucocorticoid injection into the intra-articular (IA) cavity provides potential short-term analgesia and anti-inflammatory effects, but long-term IA injections cause loss of cartilage. Synovial mesenchymal stem cells (MSCs) reportedly promote cartilage proliferation and increase cartilage content. METHODS: CD90+ MCS-derived micro-vesicle (CD90@MV)-coated nanoparticle (CD90@NP) was developed. CD90+ MCSs were extracted from human synovial tissue. Cytochalasin B (CB) relaxed the interaction between the cytoskeleton and the cell membranes of the CD90+ MCSs, stimulating CD90@MV secretion. Poly (lactic-co-glycolic acid) (PLGA) nanoparticle was coated with CD90@MV, and a model glucocorticoid, triamcinolone acetonide (TA), was encapsulated in the CD90@NP (T-CD90@NP). The chondroprotective effect of T-CD90@NP was validated in rabbit and rat OA models. RESULTS: The CD90@MV membrane proteins were similar to that of CD90+ MCSs, indicating that CD90@MV bio-activity was similar to the cartilage proliferation-inducing CD90+ MCSs. CD90@NP binding to injured primary cartilage cells was significantly stronger than to erythrocyte membrane-coated nanoparticles (RNP). In the rabbit OA model, the long-term IA treatment with T-CD90@NP showed significantly enhanced repair of damaged cartilage compared to TA and CD90+ MCS treatments. In the rat OA model, the short-term IA treatment with T-CD90@NP showed effective anti-inflammatory ability similar to that of TA treatment. Moreover, the long-term IA treatment with T-CD90@NP induced cartilage to restart the cell cycle and reduced cartilage apoptosis. T-CD90@NP promoted the regeneration of chondrocytes, reduced apoptosis via the FOXO pathway, and influenced type 2 macrophage polarization to regulate inflammation through IL-10. CONCLUSION: This study confirmed that T-CD90@NP promoted chondrocyte proliferation and anti-inflammation, improving the effects of a clinical glucocorticoid treatment plan.

Another Record: Ocean Warming Continues through 2021 despite La Niña Conditions.

The increased concentration of greenhouse gases in the atmosphere from human activities traps heat within the climate system and increases ocean heat content (OHC). Here, we provide the first analysis of recent OHC changes through 2021 from two international groups. The world ocean, in 2021, was the hottest ever recorded by humans, and the 2021 annual OHC value is even higher than last year's record value by 14 ± 11 ZJ (1 zetta J = 1021 J) using the IAP/CAS dataset and by 16 ± 10 ZJ using NCEI/NOAA dataset. The long-term ocean warming is larger in the Atlantic and Southern Oceans than in other regions and is mainly attributed, via climate model simulations, to an increase in anthropogenic greenhouse gas concentrations. The year-to-year variation of OHC is primarily tied to the El Niño-Southern Oscillation (ENSO). In the seven maritime domains of the Indian, Tropical Atlantic, North Atlantic, Northwest Pacific, North Pacific, Southern oceans, and the Mediterranean Sea, robust warming is observed but with distinct inter-annual to decadal variability. Four out of seven domains showed record-high heat content in 2021. The anomalous global and regional ocean warming established in this study should be incorporated into climate risk assessments, adaptation, and mitigation.

[Ultra-performance liquid chromatography for determination of the contents of biogenic amines in the seminal plasma].

OBJECTIVE: To establish an ultra-performance liquid chromatography (UPLC) method for determination of the contents of the three biogenic amines putacine, spermidine and spermine in human seminal plasma. METHODS: Seminal plasma samples were extracted with 5% trichloroacetic acid and processed by pre-column derivatization with dansyl chloride. Chromatographic separation was performed with a C18 (2.1×50 mm,1.7 µm) chromatographic column using water and acetonitrile for mobile-phase gradient elution at a flow rate of 0.3 ml/min, a detection wavelength of 245 nm, a column temperature of 35℃ and an injection volume was 3.0 µl. The contents of putacine, spermidine and spermine in the seminal plasma of 52 healthy sperm donors (the normal group) and 23 azoospermia patients (the AS group) were measured, and their correlation with routine semen parameters were analyzed. RESULTS: The three biogenic amines showed a good linearity (r ≥ 0.999), with a lower detection limit of 0.03－0.08 µg/ml. The relative standard deviation (RSD) of precision was ≤ 0.72% and the average recovery rate was 79.74%－108.87%. The normal group, compared with the AS patients, showed significantly higher contents of putrescine (ï¼»8.19 ± 7.85ï¼½ vs ï¼»2.43 ± 1.38ï¼½ mg/ml, P < 0.05), spermidine (ï¼»77.30 ± 32.58ï¼½ vs ï¼»31.99 ± 16.21ï¼½ mg/ml, P < 0.05) and spermine (ï¼»246.44 ± 83.99ï¼½ vs ï¼»166.15 ± 79.28ï¼½ mg/ml, P < 0.05). However, the contents of the three biogenic amines in the seminal plasma exhibited no significant correlation with the routine semen parameters in the normal group. CONCLUSIONS: The ultra-performance liquid chromatography method we established, with the advantages of high sensitivity and reproducibility and short peak-time, can quickly and accurately determine the contents of biogenic amines in the seminal plasma.

[Correlation of seminal plasma biochemical indexes with routine semen parameters in sperm donors].

OBJECTIVE: To investigate the relationship of seminal plasma biochemical indexes with routine semen parameters and that between seminal plasma biochemical indexes. METHODS: Using the automatic biochemical analyzer, we measured the contents of neutral α-glucosidase (NAG), fructose hexokinase (Fru) , citric acid (CA), acid phosphatase (ACP), (zinc) Zn, uric acid (UA), lactase dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) in the seminal plasma of 84 sperm donors in the Human Sperm Bank of Hebei Province. We analyzed the correlation between these indexes and that between routine semen parameters and these indexes. RESULTS: Sperm concentration and total sperm count were correlated positively with the contents of seminal plasma NAG, ACP, Zn, CA, LDH and α-HBDH (P<0.05) but negatively with Fru (P<0.05), the percentage of progressively motile sperm positively with seminal plasma Zn (P<0.05), and CA positively with NAG, Zn, LDH, α-HBDH and ACP (P<0.01) but negatively with Fru (P<0.01), NAG positively with Zn, LDH, α-HBDH and ACP (P<0.05) but Fru negatively with ACP (P<0.01), Zn positively with LDH, α-HBDH and ACP (P<0.01), and LDH positively with α-HBDH and ACP (P<0.01) but UA negatively with ACP (P<0.05). CONCLUSIONS: Biochemical indexes in the seminal plasma of healthy men are not only closely related to each other, but also to some routine semen parameters.

Cytochrome P450 3A4-Mediated Bioactivation and Its Role in Nomilin-Induced Hepatotoxicity.

Nomilin is a furan-containing triterpenoid isolated from the medicinal plants of citrus. The aim of this study was to investigate the in vitro and in vivo bioactivation of nomilin and the role in nomilin-induced hepatotoxicity. Microsomal incubations of nomilin supplemented with NADPH and GSH or NAL resulted in the detection of six conjugates (M1-M6). The structures of the metabolites were characterized based on LC-HRMS and NMR. Nomilin was bioactivated to a reactive cis-butene-dial (BDA) intermediate dependent on NADPH, and this intermediate suffered from the reaction with the nucleophiles (GSH and NAL) to form stable adducts. M1-M4 were identified as pyrrole derivatives, and M5 and M6 were pyrrolinone derivatives. M1 was further chemically synthesized and characterized by 13C NMR spectroscopy. M1 was the major metabolite detected in mice bile. Pretreatment with ketoconazole significantly reduced the formation of M1 in mice bile, while pretreatment with rifampicin significantly increased the formation of M1. Chemical inhibition together with recombinant human CYP450 phenotyping demonstrated that CYP3A4 was the major enzyme contributing to the bioactivation of nomilin. Toxicity study suggested that nomilin displayed dose-dependent liver injury in mice, while tetrahydro-nomilin was found to be nonhepatotoxic. Pretreatment with ketoconazole prevented mice from nomilin-induced liver injury. The liver injury induced by nomilin was deteriorated when the mice were pretreated with rifampicin. These findings provide evidence that CYP3A4-mediated bioactivation was indispensable in nomilin-induced hepatotoxicity.

Melatonin Enhances Autophagy and Reduces Apoptosis to Promote Locomotor Recovery in Spinal Cord Injury via the PI3K/AKT/mTOR Signaling Pathway.

Spinal cord injury (SCI) leads to neuronal death resulting in central nervous system (CNS) dysfunction; however, the pathogenesis is still poorly understood. Melatonin (MT), a hormone secreted mainly by the pineal gland, is associated with neuroprotective effects against SCI. Enhanced autophagy can promote the recovery of locomotor function and reduce apoptosis after SCI. Interestingly, MT increases autophagy in SCI in vivo. Nevertheless, the ability of MT to increase autophagy and decrease apoptosis, and the potential effects on the recovery of motor neurons in the anterior horn after SCI remain to be clarified. In this study, we discovered that MT treatment improved motor function recovery in a rat SCI model. Indeed, MT upregulated the expression of the phosphatidylinositol 3-kinase (PI3K), while expression of protein kinase B (AKT) and mammalian target of rapamycin (mTOR) was downregulated after SCI. Additionally, MT increased the expression of autophagy-activating proteins, while the expression of apoptosis-activating proteins in neurons was decreased following SCI. Furthermore, autophagy was inhibited, while apoptosis was induced in SCI model rats and lipopolysaccharide (LPS)-stimulated primary neurons by treatment with MT, the PI3K inhibitor 3-methyladenine (3-MA) and mTOR inhibitor Rapamycin (Rapa). Collectively, our results suggest that MT can improve the recovery of locomotor function by enhancing autophagy as well as reducing apoptosis after SCI in rats, probably via the PI3K/AKT/mTOR signaling pathway.

Triggering of Autophagy by Baicalein in Response to Apoptosis after Spinal Cord Injury: Possible Involvement of the PI3K Activation.

High level apoptosis induced by spinal cord injury (SCI) evokes serious damage because of the loss and dysfunction of motor neurons. Our previous studies showed that inhibition of autophagy evokes the activation of apoptosis. Interestingly, Baicalein, a medicine with anti-apoptosis activity that is derived from the roots of herb Scutellaria baicalensis, largely induces autophagy by activating phosphatidylinositol 3-kinase (PI3K). In this study, we investigated the effects of intraperitoneal injection of Baicalein on autophagy and apoptosis in SCI mice and evaluated the relationship between autophagy and apoptosis. We demonstrated that Baicalein promoted the functional recovery of motor neurons at 7 d after SCI. In addition, Baicalein enhanced neuronal autophagy and the autophagy-related factor PI3K, while inhibiting the p62 protein. Baicalein treatment decreased neuronal apoptosis at 7 d after SCI. Moreover, when inhibiting autophagy, apoptosis was upgraded by Baicalein treatment after injury. Thus, Baicalein attenuated SCI by inducing autophagy to reduce apoptosis in neurons potentially via activating PI3K.

Interactions between N-ethylmaleimide-sensitive factor and GluR2 in the nucleus accumbens contribute to the expression of locomotor sensitization to cocaine.

Many studies have reported a withdrawal-dependent increase in synaptic AMPA receptor (AMPAR) levels in the nucleus accumbens (NAc) of cocaine-sensitized rats; however, the exact relationship between the expression of sensitization and altered AMPAR surface expression in the NAc has not yet been investigated. We demonstrated that the expression of behavioral sensitization was negatively controlled by N-ethylmaleimide-sensitive factor (NSF)-GluR2 interactions in the NAc. The upregulation of NSF-GluR2 interactions, which may be resulted by the increase in NSF S-nitrosylation after withdrawal from cocaine, was associated with the changes in the expression of behavioral sensitization. Disruption of NSF-GluR2 interactions in the NAc with a specific peptide, TAT-pep-R845A, increased the locomotor response of rats to cocaine by decreasing GluR2 surface insertion. In contrast, prevention of GluR2-containing AMPARs removal from synapses with Pep2-EVKI attenuated the expression of behavioral sensitization. Similarly, treatment with the nitric oxide donor, S-Nitroso-N-acetyl-DL-penicillamine (SNAP), attenuated the expression of locomotor sensitization by promoting GluR2 surface expression. This effect was mediated by the binding of S-nitrosylated NSF to GluR2, which promoted the surface expression of AMPARs. Noticeably, exogenous injection of SNAP into NAc also attenuated the expression of cocaine-induced conditioned place preference. Thus, these results indicate that increased NSF-GluR2 interactions in the NAc after withdrawal from cocaine attenuated the expression of behavioral sensitization and serves as a negative regulatory mechanism in drug-exposed individuals.

Corrigendum: Balanced biogeographic and local environmental effects determine the patterns of microbial diversity in biocrusts at multi-scales.

[This corrects the article DOI: 10.3389/fmicb.2023.1284864.].

Long Non-Coding RNA MALAT1 Protects Against Spinal Cord Injury via Suppressing microRNA-125b-5p Mediated Microglial M1 Polarization, Neuroinflammation, and Neural Apoptosis.

Our previous studies have discovered that long non-coding RNA (lncRNA) MALAT1 and its target microRNA-125b-5p (miR-125b-5p) are implicated in neurological diseases via regulating neuroinflammation and neuronal injury. This study aimed to further explore the relationship between lncRNA MALAT1 and miR-125b-5p, as well as their effect on microglial activation, neuroinflammation, and neural apoptosis in spinal cord injury (SCI). Primary microglia from Sprague Dawley rats were stimulated with lipopolysaccharide (LPS). Then, microglia were transfected with lncRNA MALAT1 overexpression or knock-down adenovirus-associated virus with or without miR-125b-5p mimic. The culture medium of microglia was incubated with primary neurons. SCI rats were established for in vivo validation. LncRNA MALAT1 expression was reduced by LPS treatment in a dose-dependent manner. LncRNA MALAT1 overexpression suppressed the microglial M1 polarization (decreased iNOS but increased ARG1), neuroinflammation (declined PTGS2, TNF-α, IL-1ß, and IL-6), and microglia-induced neural apoptosis (lower TUNEL positive cells and C-caspase3 but higher BCL2) under LPS treatment; its knock-down displayed the opposite trend. Moreover, lncRNA MALAT1 directly bound to and negatively regulated miR-125b-5p. MiR-125b-5p mimic promoted microglial M1 polarization, neuroinflammation, and microglia-induced neural apoptosis following LPS treatment; also, it could attenuate the effect of lncRNA MALAT1. Further in vivo study displayed that lncRNA MALAT1 overexpression elevated the Basso-Beattie-Bresnahan motor function score and improved neural injury. Also, in vivo validation indicated a similar effect of lncRNA MALAT1 on microglial polarization and neuroinflammation as in vitro. LncRNA MALAT1 improves SCI recovery via miR-125b-5p mediated microglial M1 polarization, neuroinflammation, and neural apoptosis.

SUMOylation-Driven mRNA Circularization Enhances Translation and Promotes Lymphatic Metastasis of Bladder Cancer.

Aberrant gene expression is a prominent feature of metastatic cancer. Translational initiation is a vital step in fine-tuning gene expression. Thus, exploring translation initiation regulators may identify therapeutic targets for preventing and treating metastasis. Herein, we identified that DHCR24 was overexpressed in lymph node (LN) metastatic bladder cancer and correlated with poor prognosis of patients. DHCR24 promoted lymphangiogenesis and LN metastasis of bladder cancer in vitro and in vivo. Mechanistically, DHCR24 mediated and recognized the SUMO2 modification at lysine 108 of hnRNPA2B1 to foster TBK1 mRNA circularization and eIF4F initiation complex assembly by enhancing hnRNPA2B1-eIF4G1 interaction. Moreover, DHCR24 directly anchored to TBK1 mRNA 3'-untranslated region to increase its stability, thus forming a feed forward loop to elevate TBK1 expression. TBK1 activated PI3K/Akt signaling to promote VEGFC secretion, resulting in lymphangiogenesis and LN metastasis. DHCR24 silencing significantly impeded bladder cancer lymphangiogenesis and lymphatic metastasis in a patient-derived xenograft model. Collectively, these findings elucidate DHCR24-mediated translation machinery that promotes lymphatic metastasis of bladder cancer and supports the potential application of DHCR24-targeted therapy for LN-metastatic bladder cancer. SIGNIFICANCE: DHCR24 is a SUMOylation regulator that controls translation initiation complex assembly and orchestrates TBK1 mRNA circularization to activate Akt/VEGFC signaling, which stimulates lymphangiogenesis and promotes lymph node metastasis in bladder cancer.

Integrin α6-containing extracellular vesicles promote lymphatic remodelling for pre-metastatic niche formation in lymph nodes via interplay with CD151.

Heterogeneous extracellular vesicles (EVs) from various types of tumours are acknowledged for inducing the formation of pre-metastatic "niches" in draining lymph nodes (LNs) to promote lymphatic metastasis. In order to identify the specific subpopulations of EVs involved, we performed high-resolution proteomic analysis combined with nanoflow cytometry of bladder cancer (BCa) tissue-derived EVs to identify a novel subset of tumour-derived EVs that contain integrin α6 (ITGA6+EVs) and revealed the positive correlation of ITGA6+EVs with the formation of pre-metastatic niche in draining LNs and lymphatic metastasis in multicentre clinical analysis of 820-case BCa patients. BCa-derived ITGA6+EVs induced E-selectin (SELE)-marked lymphatic remodelling pre-metastatic niche and promoted metastasis in draining LNs through delivering cargo circRNA-LIPAR to lymphatic endothelial cells in vivo and in vitro. Mechanistically, LIPAR linked ITGA6 to the switch II domain of RAB5A and sustained RAB5A GTP-bound activated state, thus maintaining the production of ITGA6+EVs loaded with LIPAR through endosomal trafficking. ITGA6+EVs targeted lymphatic vessels through ITGA6-CD151 interplay and released LIPAR to induce SELE overexpression-marked lymphatic remodelling pre-metastatic niche. Importantly, we constructed engineered-ITGA6 EVs to inhibit lymphatic pre-metastatic niche, which suppressed lymphatic metastasis and prolonged survival in preclinical models. Collectively, our study uncovers the mechanism of BCa-derived ITGA6+EVs mediating pre-metastatic niche and provides an engineered-EV-based strategy against BCa lymphatic metastasis.

PDGFRα+ITGA11+ fibroblasts foster early-stage cancer lymphovascular invasion and lymphatic metastasis via ITGA11-SELE interplay.

Cancer-associated fibroblasts (CAFs) exhibit considerable heterogeneity in advanced cancers; however, the functional annotation and mechanism of CAFs in early-stage cancers remain elusive. Utilizing single-cell RNA sequencing and spatial transcriptomic, we identify a previously unknown PDGFRα+ITGA11+ CAF subset in early-stage bladder cancer (BCa). Multicenter clinical analysis of a 910-case cohort confirms that PDGFRα+ITGA11+ CAFs are associated with lymphovascular invasion (LVI) and poor prognosis in early-stage BCa. These CAFs facilitate LVI and lymph node (LN) metastasis in early-stage BCa, as evidenced in a PDGFRα+ITGA11+ CAFs-specific deficient mouse model. Mechanistically, PDGFRα+ITGA11+ CAFs promote lymphangiogenesis via recognizing ITGA11 surface receptor SELE on lymphatic endothelial cells to activate SRC-p-VEGFR3-MAPK pathway. Further, CHI3L1 from PDGFRα+ITGA11+ CAFs aligns the surrounding matrix to assist cancer cell intravasation, fostering early-stage BCa LVI and LN metastasis. Collectively, our study reveals the crucial role of PDGFRα+ITGA11+ CAFs in shaping metastatic landscape, informing the treatment of early-stage BCa LVI.

Emergence of decadal linkage between Western Australian coast and Western-central tropical Pacific.

The impact of interbasin linkage on the weather/climate and ecosystems is significantly broader and profounder than that of only appearing in an individual basin. Here, we reveal that a decadal linkage of sea surface temperature (SST) has emerged between western Australian coast and western-central tropical Pacific since 1985, associated with continuous intensification of decadal variabilities (8-16 years). The rapid SST changes in both tropical Indian Ocean and Indo-Pacific warm pool in association to greenhouse gases and volcanoes are emerging factors resulting in enhanced decadal co-variabilities between these two regions since 1985. These SST changes induce enhanced convection variability over the Maritime Continent, leading to stronger easterlies in the western-central tropical Pacific during the warm phase off western Australian coast. The above changes bring about cooling in the western-central tropical Pacific and strengthened Leeuwin Current and anomalous cyclonic wind off western Australian coast, and ultimately resulting in enhanced coupling between these two regions. Our results suggest that enhanced decadal interbasin connections can offer further understanding of decadal changes under future warmer conditions.

Balanced biogeographic and local environmental effects determine the patterns of microbial diversity in biocrusts at multi-scales.

Introduction: Biodiversity maintenance and its underlying mechanisms are central issues of ecology. However, predicting the composition turnovers of microbial communities at multiple spatial scales remains greatly challenging because they are obscured by the inconsistent impacts of climatic and local edaphic conditions on the assembly process. Methods: Based on the Illumina MeSeq 16S/18S rRNA sequencing technology, we investigated soil bacterial and eukaryotic communities in biocrusts with different successional levels at a subcontinental scale of Northern China. Results: Results showed that irrespective of spatial scale, bacterial α diversity increased but eukaryotic diversity decreased with the primary succession, whereas both ß diversities decreased at the subcontinental scale compared with smaller scales, indicating that the biogeographic pattern of soil microorganisms was balanced by successional convergence and distance decay effect. We found that the convergence of bacterial and eukaryotic communities was attributed to the turnovers of generalist and specialist species, respectively. In this process, edaphic and climatic factors showed unique roles in the changes of diversity at local/subcontinental scales. Moreover, the taxonomic diversity tended to be more susceptible to climatic and edaphic conditions, while biotic factors (photosynthesis and pigments) were more important to phylogenetic diversity. Conclusion: Taken together, our study provided comprehensive insights into understanding the pattern of microbial diversity at multiple spatial scales of drylands.

Minimum Quantity Lubrication Jet Noise: Passive Control.

Jet noise is a common problem in minimum quantity lubrication (MQL) technology. This should be given great attention because of its serious impacts on the physical and mental health of the operators. In this study, a micro-grooved nozzle is proposed based on the noise reduction concept of biological micro-grooves. The flow field and acoustic characteristics of an original nozzle and a micro-grooved nozzle were investigated numerically to help better understand the noise reduction mechanism. The reasons for noise generation and the effects of the length (L), width (W) and depth (δ) of the micro-grooves on noise reduction were analyzed. It was found that jet noise is generated by the large-scale vortex ring structure and the pressure fluctuations caused by its motion. The overall sound pressure level (OASPL) decreased with the increases in W and δ, and increased with the increase in L. Among of them, δ has the greatest effect on noise reduction. The maximum noise reduction achieved was 6.66 dB, as verified by the OASPL test. Finally, the noise reduction mechanism was discussed in terms of the flow field, vorticity and the frequency characteristics. Micro-grooves can enhance the mixing of airflow inside the nozzle and accelerate the process of large-scale vortices breaking into smaller-scale vortices. It also reduces the sound pressure level (SPL) of middle frequencies, as well as the SPL of high frequencies on specific angles.

Targeting lncRNA NEAT1 Hampers Alzheimer's Disease Progression.

Long noncoding RNA nuclear enriched abundant transcript 1 (lnc-NEAT1) is closely implicated in neurological diseases, while its implication in Alzheimer's disease (AD) is rarely reported. This study aimed to investigate the effect of lnc-NEAT1 knockdown on neuron injury, inflammation, and oxidative stress in AD, as well as its interaction with downstream targets and pathways. APPswe/PS1dE9 transgenic mice were injected with negative control or lnc-NEAT1 interference lentivirus. Besides, AD cellular model was constructed by amyloid ß treatment in mice primary neuron cells; then, knockdown of lnc-NEAT1 and microRNA-193a was performed alone or in combination. In vivo experiments revealed that Lnc-NEAT1 knockdown improved cognition in AD mice reflected by Morrison water maze and Y-maze assays. Besides, lnc-NEAT1 knockdown reduced injury and apoptosis, decreased inflammatory cytokine levels, repressed oxidative stress level, and activated adenosine cyclophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) and nuclear factor erythroid 2-related factor 2 (NRF2)/nicotinamide adenine dinucleotide phosphate dehydrogenase 1 (NQO1) pathways in hippocampi of AD mice. Notably, lnc-NEAT1 down-regulated microRNA-193a both in vitro and in vivo and acted as a decoy of microRNA-193a. In vitro experiments showed that lnc-NEAT1 knockdown decreased apoptosis and oxidative stress, improved cell viability, also activated CREB/BDNF and NRF2/NQO1 pathways in AD cellular model. Meanwhile, microRNA-193a knockdown showed the opposite effects, which also attenuated lnc-NEAT1 knockdown-mediated reduction in injury, oxidative stress, and CREB/BDNF and NRF2/NQO1 pathways of AD cellular model. In conclusion, lnc-NEAT1 knockdown reduces neuron injury, inflammation, and oxidative stress through activating microRNA-193a mediated CREB/BDNF and NRF2/NQO1 pathways in AD.

Alpha lipoic acid-loaded electrospun fibrous patch films protect heart in acute myocardial infarction mice by inhibiting oxidative stress.

Oxidative stress, characterized by excessive accumulation of reactive oxygen species (ROS), is involved in acute myocardial infarction (AMI)-related pathological processes and vascular reperfusion therapy injury. Alpha lipoic acid (LA) exhibits excellent antioxidant properties, however, its application is limited by inherent characteristics, including rapid clearance and extensive volume distribution. In this study, we hypothesized that scavenging cardiac ROS using adequately delivered LA could promote heart repair. Here, we report a new strategy for dynamic-release LA to treat AMI disease. In particular, this involves using poly(lactic-co-glycolic) (PLGA) copolymers as carriers to form a thin film (LA@PLGA) via electrospinning technology to achieve controlled release of LA, which essentially blocking local ROS production in damaged hearts. The drug-loading capacity and capsulation efficiency of this compound film could be regulated by determining the dose proportions of LA and PLGA. The incubation of LA@PLGA showed strong anti-oxidative activity and anti-apoptosis effect in hydrogen peroxide-administered primary cardiomyocytes. Patching LA@PLGA on the infarcted cardiac surfaces of AMI mice dramatically improved heart functions and reduced cardiac fibrosis throughout ventricular remodeling process. Importantly, the attenuation of detrimental pathologies was observed, including oxidative stress, senescence, DNA damage, cytokine-related processes, apoptosis, and ferroptosis. These results suggest that PLGA-carried LA can reduce ROS damage and restore heart function after myocardial damage, demonstrating a great potential for LA drugs in treating AMI disease.