Assessing progress towards sustainable development over space and time.

To address global challenges1-4, 193 countries have committed to the 17 United Nations Sustainable Development Goals (SDGs)5. Quantifying progress towards achieving the SDGs is essential to track global efforts towards sustainable development and guide policy development and implementation. However, systematic methods for assessing spatio-temporal progress towards achieving the SDGs are lacking. Here we develop and test systematic methods to quantify progress towards the 17 SDGs at national and subnational levels in China. Our analyses indicate that China's SDG Index score (an aggregate score representing the overall performance towards achieving all 17 SDGs) increased at the national level from 2000 to 2015. Every province also increased its SDG Index score over this period. There were large spatio-temporal variations across regions. For example, eastern China had a higher SDG Index score than western China in the 2000s, and southern China had a higher SDG Index score than northern China in 2015. At the national level, the scores of 13 of the 17 SDGs improved over time, but the scores of four SDGs declined. This study suggests the need to track the spatio-temporal dynamics of progress towards SDGs at the global level and in other nations.

Deletion of the sugar importer gene OsSWEET1b accelerates sugar starvation-promoted leaf senescence in rice.

Leaf senescence is a combined response of plant cells stimulated by internal and external signals. Sugars acting as signaling molecules or energy metabolites can influence the progression of leaf senescence. Both sugar starvation and accumulation can promote leaf senescence with diverse mechanisms that are reported in different species. Sugars Will Eventually be Exported Transporters (SWEETs) are proposed to play essential roles in sugar transport, but whether they have roles in senescence and the corresponding mechanism are unclear. Here, we functionally characterized a sugar transporter, OsSWEET1b, which transports sugar and promotes senescence in rice (Oryza sativa L.). OsSWEET1b could import glucose and galactose when heterologously expressed in Xenopus oocytes and translocate glucose and galactose from the extracellular apoplast into the intracellular cytosol in rice. Loss of function of OsSWEET1b decreased glucose and galactose accumulation in leaves. ossweet1b mutants showed accelerated leaf senescence under natural and dark-induced conditions. Exogenous application of glucose and galactose complemented the defect of OsSWEET1b deletion-promoted senescence. Moreover, the senescence-activated transcription factor OsWRKY53, acting as a transcriptional repressor, genetically functions upstream of OsSWEET1b to suppress its expression. OsWRKY53-overexpressing plants had attenuated sugar accumulation, exhibiting a similar phenotype as the ossweet1b mutants. Our findings demonstrate that OsWRKY53 downregulates OsSWEET1b to impair its influx transport activity, leading to compromised sugar accumulation in the cytosol of rice leaves where sugar starvation promotes leaf senescence.

Prolactin receptor potentiates chemotherapy through miRNAs-induced G6PD/TKT inhibition in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with a notoriously dismal prognosis. As a competitive inhibitor of DNA synthesis, gemcitabine is the cornerstone drug for treating PDAC at all stages. The therapeutic effect of gemcitabine, however, is often hindered by drug resistance, and the underlying mechanisms remain largely unknown. It is unclear whether their response to chemotherapeutics is regulated by endocrine regulators, despite the association between PDAC risk and endocrine deregulation. Here, we show that prolactin receptor (PRLR) synergizes with gemcitabine in both in vitro and in vivo treatment of PDAC. Interestingly, PRLR promotes the expression of miR-4763-3p and miR-3663-5p, two novel miRNAs whose functions are unknown. Furthermore, the analysis of transcriptome sequencing data of tumors from lactating mouse models enriches the PPP pathway, a multifunctional metabolic pathway. In addition to providing energy, the PPP pathway mainly provides a variety of raw materials for anabolism. We demonstrate that two key enzymes of the pentose phosphate pathway (PPP), G6PD and TKT, are directly targeted by miR-4763-3p and miR-3663-5p. Notably, miR-4763-3p and miR-3663-5p diminish the nucleotide synthesis of the PPP pathway, thereby increasing gemcitabine sensitivity. As a result, PRLR harnesses these two miRNAs to suppress PPP and nucleotide synthesis, subsequently elevating the gemcitabine sensitivity of PDAC cells. Also, PDAC tissues and tumors from LSL-KrasG12D/+, LSL-Trp53R172H/+, and PDX1-cre (KPC) mice exhibit downregulation of PRLR. Bisulfite sequencing of PDAC tissues revealed that PRLR downregulation is due to epigenetic methylation. In this study, we show for the first time that the endocrine receptor PRLR improves the effects of gemcitabine by boosting two new miRNAs that block the PPP pathway and nucleotide synthesis by inhibiting two essential enzymes concurrently. The PRLR-miRNAs-PPP axis may serve as a possible therapeutic target to supplement chemotherapy advantages in PDAC.

Overcoming multi-drug resistance in SCLC: a synergistic approach with venetoclax and hydroxychloroquine targeting the lncRNA LYPLAL1-DT/BCL2/BECN1 pathway.

BACKGROUND: Small cell lung cancer (SCLC) stands as one of the most lethal malignancies, characterized by a grim diagnosis and prognosis. The emergence of multi-drug resistance poses a significant hurdle to effective therapy. Although previous studies have implicated the long noncoding RNA LYPLAL1-DT in the tumorigenesis of SCLC, the precise role of the highly expressed LYPLAL1-DT in SCLC chemoresistance and the underlying mechanism remain inadequately understood. METHODS: cDDP-, VP-16- and PTX-resistant SCLC cells lines were established. The viabilities of SCLC cells were assessed by CCK-8 assay in vitro and xenograft tumor formation assay in vivo. Apoptosis was evaluated by FACS, Western blot and JC-1 fluorescence staining, while autophagy was explored via autophagic flux detection under confocal microscopy and autophagic vacuole investigation under transmission electron microscopy (TEM). The functional role and mechanism of LYPLAL1-DT were further investigated by gain- and loss-of-function assays in vitro. Furthermore, the therapeutic efficacy of the combination of venetoclax and HCQ with cDDP, VP-16 or PTX was evaluated by cell line, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mice model. RESULTS: Our findings revealed that LYPLAL1-DT is upregulated in chemoresistant SCLC cell lines. Gain- and loss-of-function assays demonstrated that LYPLAL1-DT impairs sensitivity to cDDP, VP-16, or PTX both in vitro and in vivo. Overexpression of LYPLAL1-DT significantly enhanced autophagy and inhibited apoptosis in SCLC cells. Further analyses, including RIP and RNA pull-down assays, revealed that LYPLAL1-DT promotes the expression of BCL2 by sponging miR-204-5p and is implicated in the assembly of the autophagy-specific complex (BECN1/PtdIns3K complex). Combining venetoclax and HCQ with cDDP, VP-16, or PTX effectively mitigated chemoresistance in SCLC cells and suppressed tumor growth in CDX and PDX models without inducing obvious toxic effects. CONCLUSIONS: Our findings demonstrate that upregulation of LYPLAL1-DT sequesters apoptosis through the LYPLAL1-DT/miR-204-5p/BCL2 axis and promotes autophagy by facilitating the assembly of the BECN1/PtdIns3K complex, thereby mediating multi-drug resistance of SCLC. The triple combination of venetoclax, HCQ, in conjunction with cDDP, VP-16 or PTX overcomes refractory SCLC, shedding light on a potential therapeutic target for combating SCLC chemoresistance.

Enhanced Oxidation-Resistant and Conductivity in MXene Films with Seamless Heterostructure.

MXene-based films have garnered significant attention for their remarkable electrical and mechanical properties. Nevertheless, the practical application of MXene is impeded by its intrinsic instability caused by spontaneous oxidation. The traditional anti-oxidative strategies frequently lead to a compromise in stability, electrical conductivity, and mechanical properties. In this study, a novel approach is proposed involving metal nano-armoring, wherein a copper layer with nano thickness is deposited onto MXene film surfaces to establish a uniform and seamless heterogeneous interface (MXene@Cu). The precise tunability and uniformity of this heterostructure are consistently demonstrated through both theoretical calculations and experimental results. The MXene@Cu films exhibit exceptional electrical conductivity of 1.17 × 106 S m-1, electromagnetic interference shielding effectiveness of 77.1 dB, and tensile strength of 43.4 MPa. More importantly, this heterostructure significantly improves MXene's stability against oxidation. After exposure to air for 30 days, the resultant MXene@Cu films exhibit a remarkable conductivity retention of 72.0%, significantly exceeding that of pristine MXene films (44.3%). This scalable synthesis approach holds significant promise for electronic device applications, particularly in electromagnetic shielding and thermal management.

ELAVL4 promotes the tumorigenesis of small cell lung cancer by stabilizing LncRNA LYPLAL1-DT and enhancing profilin 2 activation.

Small cell lung cancer (SCLC) is one of the most malignant tumors that has an extremely poor prognosis. RNA-binding protein (RBP) and long noncoding RNA (lncRNA) have been shown to be key regulators during tumorigenesis as well as lung tumor progression. However, the role of RBP ELAVL4 and lncRNA LYPLAL1-DT in SCLC remains unclear. In this study, we verified that lncRNA LYPLAL1-DT acts as an SCLC oncogenic lncRNA and was confirmed in vitro and in vivo. Mechanistically, LYPLAL1-DT negatively regulates the expression of miR-204-5p, leading to the upregulation of PFN2, thus, promoting SCLC cell proliferation, migration, and invasion. ELAVL4 has been shown to enhance the stability of LYPLAL1-DT and PFN2 mRNA. Our study reveals a regulatory pathway, where ELAVL4 stabilizes PFN2 and LYPLAL1-DT with the latter further increasing PFN2 expression by blocking the action of miR-204-5p. Upregulated PFN2 ultimately promotes tumorigenesis and invasion in SCLC. These findings provide novel prognostic indicators as well as promising new therapeutic targets for SCLC.

Visualization of nonsmall-cell lung cancer by near-infrared fluorescence imaging with tumor-targeting peptide ABT-510.

Nonsmall-cell lung cancer (NSCLC) is the most frequent type of lung cancer, with early surgical treatment proving vital for prolonged patient survival. However, precise visualization of NSCLC remains a challenge due to limited molecular imaging probes, the unique anatomical structure of the lungs, and respiratory movement interference. In this study, we investigated the potential utility of CD36, which is highly expressed in NSCLC, as an imaging target. A selective and water-soluble fluorescent probe, MPA-ABT-510, was successfully constructed by coupling ABT-510 with MPA, a near-infrared (NIR) fluorescent dye. Molecular docking analysis shows that MPA-ABT-510 possesses strong binding affinity to the CD36 protein, with specific hydrogen bond interactions at defined amino acid residues. In vitro assays reveals that the fluorescein isothiocyanate-labeled peptide ABT-510 specifically binds to the CD36-high expressing NSCLC cell lines H1299 and A549. In vivo imaging verifies that the MPA-ABT-510 efficiently accumulates in the tumor site with a distinct fluorescent signal. Ex vivo imaging revealed that tumor-to-lung fluorescence ratios for subcutaneous and orthotopic H1299 mouse models were 7.19 ± 0.73 and 1.91 ± 0.42, respectively, while those for A549 mice were 5.53 ± 0.64 and 1.77 ± 0.41, respectively. Biodistribution analysis demonstrated efficient MPA-ABT-510 uptake in H1299 and A549 liver metastases models with tumor-to-liver fluorescence ratios of 2.47 ± 0.48 and 2.19 ± 0.22, respectively. High MPA-ABT-510 accumulation was evident in A549 intestinal metastases models, as evidenced by tumor-to-colorectal fluorescence ratios of 4.27 ± 0.11. MPA-ABT-510 exhibits superior imaging capabilities with minimal safety concerns, so it is a promising candidate for NSCLC surgical navigation.

An Innovative Approach to Alleviate Zinc Oxide Nanoparticle Stress on Wheat through Nanobubble Irrigation.

The extensive utilization of zinc oxide nanoparticles in consumer products and the industry has led to their substantial entry into the soil through air and surface runoff transportation, which causes ecotoxicity in agro-ecosystems and detrimental effects on crop production. Nanobubbles (diameter size < 1 µm) have many advantages, such as a high surface area, rapid mass transfer, and long retention time. In this study, wheat seedlings were irrigated with a 500 mg L-1 zinc oxide nanoparticle solution delivered in the form of nanobubble watering (nanobubble-ZnO-NPs). We found that nanobubble watering improved the growth and nutrient status of wheat exposed to zinc oxide nanoparticles, as evidenced by increased total foliar nitrogen and phosphorus, along with enhanced leaf dry mass per area. This effect can be attributed to nanobubbles disassembling zinc oxide aggregates formed due to soil organic carbon, thereby mitigating nutrient absorption limitations in plants. Furthermore, nanobubbles improved the capability of soil oxygen input, leading to increased root activity and glycolysis efficiency in wheat roots. This work provides valuable insights into the influence of nanobubble watering on soil quality and crop production and offers an innovative approach for agricultural irrigation that enhances the effectiveness and efficiency of water application.

A comparative study of esketamine-dexmedetomidine and sufentanil-dexmedetomidine for sedation and analgesia in lung tumor percutaneous radiofrequency ablation (PRFA): a randomized double-blind clinical trial.

OBJECTIVE: To observe and evaluate the effectiveness and safety of Esketamine or Sufentanil combined with Dexmedetomidine for sedation and analgesia in lung tumor percutaneous radiofrequency ablation (PRFA) to provide a clinical basis for the optimization of sedation and analgesia in lung tumor PRFA protocols outside the operating room. METHODS: In this trial, 44 patients aged 37 to 84 undergoing lung tumor PRFA were enrolled and assigned to Group E (n = 22, Esketamine 0.2 mg/kg) or Group S (n = 22,Sufentanil 0.1 µg/kg ). Dexmedetomidine was infused intravenously as a sedative in both groups. The modified observer's assessment of alertness and sedation scale (MOAAS), physical movement pain scale, intraoperative vital signs, anesthesia recovery time, radiologist and patient satisfaction rates, incidence of respiratory depression, and incidence of postoperative nausea and vomiting were recorded. RESULTS: Although there was no significant difference in the physical movement pain scale, blood oxygen saturation or incidence of perioperative adverse events between the two groups during ablation, the MOAAS, mean arterial pressure (MAP) and heart rate (HR) were higher in Group E than in Group S. The anesthesia recovery time was shorter in Group E than in Group S, and radiologist satisfaction was better in Group E than in Group S, but there was no significant difference between the two groups in terms of patient satisfaction. CONCLUSION: Esketamine or Sufentanil combined with Dexmedetomidine is safe for lung tumor PRFA. However, in elderly patients with multiple underlying diseases, low-dose Esketamine combined with Dexmedetomidine has fewer hemodynamic effects on patients, milder respiratory depression, shorter recovery time, and better radiologist satisfaction because of its better controllability of sedation depth. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration number#ChiCTR ChiCTR21000500 21); Date of Registration: 16/08/2021.

A noncanonical heme oxygenase specific for the degradation of c-type heme.

Heme oxygenases (HOs) play a critical role in recouping iron from the labile heme pool. The acquisition and liberation of heme iron are especially important for the survival of pathogenic bacteria. All characterized HOs, including those belonging to the HugZ superfamily, preferentially cleave free b-type heme. Another common form of heme found in nature is c-type heme, which is covalently linked to proteinaceous cysteine residues. However, mechanisms for direct iron acquisition from the c-type heme pool are unknown. Here we identify a HugZ homolog from the oligopeptide permease (opp) gene cluster of Paracoccus denitrificans that lacks any observable reactivity with heme b and show that it instead rapidly degrades c-type hemopeptides. This c-type heme oxygenase catalyzes the oxidative cleavage of the model substrate microperoxidase-11 at the ß- and/or δ-meso position(s), yielding the corresponding peptide-linked biliverdin, CO, and free iron. X-ray crystallographic analysis suggests that the switch in substrate specificity from b-to c-type heme involves loss of the N-terminal α/ß domain and C-terminal loop containing the coordinating histidine residue characteristic of HugZ homologs, thereby accommodating a larger substrate that provides its own iron ligand. These structural features are also absent in certain heme utilization/storage proteins from human pathogens that exhibit low or no HO activity with free heme. This study thus expands the scope of known iron acquisition strategies to include direct oxidative cleavage of heme-containing proteolytic fragments of c-type cytochromes and helps to explain why certain oligopeptide permeases show specificity for the import of heme in addition to peptides.

Fracture behaviour of silver nanowire films during shear deformation.

Silver nanowire films have a wide application prospect in flexible electronics, while it is a noticeable problem that the silver nanowires break due to the shear force under the mass production film cutting or extreme service conditions. In this paper, the shear fracture behaviour of silver nanowire films with different structural parameters was studied under the extreme shear failure tests. The load-displacement curve was obtained from the nano-indentation test, while the hardnessH, the elastic modulusEand the plastic properties represented by the ratio ofH3/E2of silver nanowire films with different diameters and thicknesses were calculated. On the other hand, based on the load-displacement curve, the stress-strain curve can be obtained through the finite element method simulation. The plastic properties can also be judged by the lower limit of yield strength from simulated stress-strain curve. Combined with characteristic crack propagation range, the relationship between plasticity and shear fracture was found, which was further disclosed by in-depth microstructure analysis. The results show that the better the plasticity of silver nanowire films, the stronger the resistance to shear fracture.

Channel catfish virus ORF25 and ORF63 genes are essential for viral replication in vitro.

The channel catfish virus (CCV) is a lethal pathogen to aquatic animals that can provoke severe haemorrhagic disease in juvenile channel catfish. Although the CCV genome has been fully sequenced, the molecular mechanisms of CCV infection and pathogenesis are less well known. Genomic DNA replication is a necessary and key event for the CCV life cycle. In this study, the impacts of the putative helicase and primase encoded by viral ORF25 and ORF63 on CCV genome replication and infection were evaluated in channel catfish ovary (CCO) cells. The results showed that the number of CCV genome copies was decreased significantly in virus-infected CCO cells after knockdown of ORF25 and ORF63 using RNA interference. In contrast, the overexpression of ORF25 and ORF63 led to slight increase in the number of virus genome copies. Consistent with the above results, the present results also showed that the expressions of CCV true-late genes which strictly depend on viral DNA replication, were significantly increased or repressed by overexpression or RNA interference targeting viral ORF25 and ORF63 genes in virus-infected CCO cells. In addition, knockdown of ORF25 and ORF63 remarkably inhibited CCV-induced cytopathic effects and decreased progeny virus titres in CCO cells. Moreover, transmission electron microscopy observation of CCO cells infected with CCV accompanied by siRNA targeting the viral ORF25 and ORF63 genes showed that the number of virus particles was remarkably reduced. Taken together, these results indicated that ORF25 and ORF63 are essential for regulating CCV genome replication and CCV-induced infection. Our findings will provide an understanding of the replication mechanisms of CCV and contribute to the development of antiviral strategies for controlling CCV infection in channel catfish culture.

A wound alkalinity measurement to predict non-healing wound outcomes.

OBJECTIVE: As wound pH could influence wound healing rates, this study examined the alkalinity of the entire wound during patients' follow-up visits to predict the final non-healing outcome. METHOD: Wound alkalinity of patients with diabetic foot ulcers (DFUs), venous leg ulcers, and other wounds during three follow-up visits within a four week period was recorded. All wounds were followed until 12 weeks to confirm that healed wounds did not relapse. The alkalinity of various wounds over multiple visits with varying durations was compared with final wound status to assess whether one-time wound alkalinity measurement could predict non-healing wounds. The effect of wound types, infection, age and sex on such determinations was also studied. RESULTS: A total of 96 patients were included in this study. Based on probability variations of pre- and post-test non-healing outcomes from multiple visits over 12 weeks, second visit assessment gave the highest increase in risk of non-healing for an alkaline test result (+8.0%) and decrease in risk of non-healing for a non-alkaline test result (-19.7%). Moreover, a second visit (7-21 days from first visit) showed a greater change in risk for non-healing based on alkaline and non-alkaline test results (+15.7% and -38.1% respectively), compared with a visit within seven days (+6.3% and -12.5%, respectively). Wound type, infection, age and sex did not affect the prognostic ability of wound alkalinity. CONCLUSION: The results of this study support that a single wound alkalinity measurement during the second visit (7-21 days from first visit) can be used to predict non-healing wounds. Wound alkalinity may be routinely assessed to predict non-healing wounds and to determine whether the wounds are healing as expected following initial treatment.

Clioquinol Attenuates Pulmonary Fibrosis through Inactivation of Fibroblasts via Iron Chelation.

Strict control of iron homeostasis is critical for the maintenance of normal lung function. Iron accumulates in the lungs of patients with idiopathic pulmonary fibrosis (PF), but the characteristics of iron metabolism in the pathogenesis of PF and related targeting therapeutics are not well studied. In this study, we investigated the cellular and molecular characteristics of iron metabolism in fibrotic lungs and further explored the efficacy of clioquinol (CQ) for the treatment of PF as well as its functional mechanism. Iron aggregates accumulated in the lungs of patients with idiopathic PF, and FTL (ferritin light chain) transcripts were increased in their pulmonary fibroblasts. In the bleomycin (BLM)-induced PF (BLM-PF) mouse model, pulmonary iron accumulation is a very early and concomitant event of PF. Labile iron pool levels in both fibroblasts and macrophages from the BLM-PF model were elevated, and iron metabolism was dysregulated. CQ attenuated PF induced by BLM and FITC, and iron-saturated CQ did not alleviate BLM-PF. Furthermore, CQ inhibited the activation of fibroblasts, including proliferation, fibrotic differentiation, proinflammatory cytokine secretion, and migration. In conclusion, our study demonstrated that CQ, acting as an iron chelator, attenuates experimental PF through inactivation of fibroblasts, providing support for targeting iron metabolism as a basis for PF treatment.

Respiratory axon regeneration in the chronically injured spinal cord.

Promoting the combination of robust regeneration of damaged axons and synaptic reconnection of these growing axon populations with appropriate neuronal targets represents a major therapeutic goal following spinal cord injury (SCI). A key impediment to achieving this important aim includes an intrinsic inability of neurons to extend axons in adult CNS, particularly in the context of the chronically-injured spinal cord. We tested whether an inhibitory peptide directed against phosphatase and tensin homolog (PTEN: a central inhibitor of neuron-intrinsic axon growth potential) could restore inspiratory diaphragm function by reconnecting critical respiratory neural circuitry in a rat model of chronic cervical level 2 (C2) hemisection SCI. We found that systemic delivery of PTEN antagonist peptide 4 (PAP4) starting at 8 weeks after C2 hemisection promoted substantial, long-distance regeneration of injured bulbospinal rostral Ventral Respiratory Group (rVRG) axons into and through the lesion and back toward phrenic motor neurons (PhMNs) located in intact caudal C3-C5 spinal cord. Despite this robust rVRG axon regeneration, PAP4 stimulated only minimal recovery of diaphragm function. Furthermore, re-lesion through the hemisection site completely removed PAP4-induced functional improvement, demonstrating that axon regeneration through the lesion was responsible for this partial functional recovery. Interestingly, there was minimal formation of putative excitatory monosynaptic connections between regrowing rVRG axons and PhMN targets, suggesting that (1) limited rVRG-PhMN synaptic reconnectivity was responsible at least in part for the lack of a significant functional effect, (2) chronically-injured spinal cord presents an obstacle to achieving synaptogenesis between regenerating axons and post-synaptic targets, and (3) addressing this challenge is a potentially-powerful strategy to enhance therapeutic efficacy in the chronic SCI setting. In conclusion, our study demonstrates a non-invasive and transient pharmacological approach in chronic SCI to repair the critically-important neural circuitry controlling diaphragmatic respiratory function, but also sheds light on obstacles to circuit plasticity presented by the chronically-injured spinal cord.

LAR inhibitory peptide promotes recovery of diaphragm function and multiple forms of respiratory neural circuit plasticity after cervical spinal cord injury.

Chondroitin sulfate proteoglycans (CSPGs), up-regulated in and around the lesion after traumatic spinal cord injury (SCI), are key extracellular matrix inhibitory molecules that limit axon growth and consequent recovery of function. CSPG-mediated inhibition occurs via interactions with axonal receptors, including leukocyte common antigen- related (LAR) phosphatase. We tested the effects of a novel LAR inhibitory peptide in rats after hemisection at cervical level 2, a SCI model in which bulbospinal inspiratory neural circuitry originating in the medullary rostral ventral respiratory group (rVRG) becomes disconnected from phrenic motor neuron (PhMN) targets in cervical spinal cord, resulting in persistent partial-to-complete diaphragm paralysis. LAR peptide was delivered by a soaked gelfoam, which was placed directly over the injury site immediately after C2 hemisection and replaced at 1 week post-injury. Axotomized rVRG axons originating in ipsilateral medulla or spared rVRG fibers originating in contralateral medulla were separately assessed by anterograde tracing via AAV2-mCherry injection into rVRG. At 8 weeks post-hemisection, LAR peptide significantly improved ipsilateral hemidiaphragm function, as assessed in vivo with electromyography recordings. LAR peptide promoted robust regeneration of ipsilateral-originating rVRG axons into and through the lesion site and into intact caudal spinal cord to reach PhMNs located at C3-C5 levels. Furthermore, regenerating rVRG axons re-established putative monosynaptic connections with their PhMNs targets. In addition, LAR peptide stimulated robust sprouting of both modulatory serotonergic axons and contralateral-originating rVRG fibers within the PhMN pool ipsilateral/caudal to the hemisection. Our study demonstrates that targeting LAR-based axon growth inhibition promotes multiple forms of respiratory neural circuit plasticity and provides a new peptide-based therapeutic strategy to ameliorate the devastating respiratory consequences of SCI.

A non-contact device for fast screening of wound infections.

Screening for wound infection relies on the expertise of the provider. Clinical diagnosis of infections based on wound swab/biopsy results often takes a few days and may not assess the full wound. There is a need for a non-invasive tool that can quickly and accurately diagnose wound infection. Leukocyte esterase strips are used to identify various infectious diseases. However, it is not clear whether infected wounds also have elevated leukocyte esterase activities as compared with non-infected wounds. To achieve the objective, a device was developed to detect elevated leukocyte esterase activities in wounds by measuring wound exudates adsorbed onto wound dressings in 3 minutes. The efficacy of the device in assessing leukocyte esterase activities across various chronic wounds was tested. Such measurements were unaffected by the type of underlying wound dressing. By correlating the device outputs with clinical adjudication of infection, we found that this device had high positive predictive values for diagnosing wound infection in a wide variety of chronic wounds. In addition, a positive device output increases the probability of detecting infected wounds, while the negative device output reduces the probability of detecting infected wounds. This rapid non-contact and disposable diagnostic tool may serve as a rapid and accurate indication of infection in the chronic wound.

Melatonin reduces nanoplastic uptake, translocation, and toxicity in wheat.

With increasing plastic production and consumption, large amounts of polystyrene nanoplastics are accumulated in soil due to improper disposal causing pollution and deleterious effects to environment. However, little information is available about how to alleviate the adverse impacts of nanoplastics on crops. In this study, the involvement of melatonin in modulating nanoplastic uptake, translocation, and toxicity in wheat plant was investigated. The results demonstrated that exogenous melatonin application reduced the nanoplastic uptake by roots and their translocation to shoots via regulating the expression of genes associated with aquaporin, including the upregulation of the TIP2-9, PIP2, PIP3, and PIP1.2 in leaves and TIP2-9, PIP1-5, PIP2, and PIP1.2 in roots. Melatonin activated the ROS scavenging system to maintain a better redox homeostasis and ameliorated the negative effects of nanoplastics on carbohydrate metabolism, hence ameliorated the plant growth and enhanced the tolerance to nanoplastics toxicity. This process was closely related to the exogenous melatonin application induced melatonin accumulation in leave. These results suggest that melatonin could alleviate the adverse effects of nanoplastics on wheat, and exogenous melatonin application might be used as a promising management strategy to sustain crop production in the nanoplastic-polluted soils.

Diagnostic value of MRI-DWI signal intensity value combined with serum PGI, PGII and CA199 in early gastric cancer.

To explore the diagnostic value of MRI-DWI signal intensity value combined with serum PGI. PGII and CA199 in early gastric cancer. Sixty cases of gastric cancer patients admitted to our hospital from December 2019 to December 2020 were selected as the gastric cancer group and 80 cases of healthy volunteers who underwent physical examination in our hospital during the same period were selected as the healthy group. All the 60 patients underwent MRI-DWI examination, and the pathological diagnosis results were regarded as the gold standard. MRI-DWI images, MRI-DWI signal intensity values of patients with different degrees of gastric cancer differentiation. Serum PGI, PGII and CA199 levels of subjects in the two groups were compared. AUC was used to evaluate the diagnostic value of MRI-DWI signal intensity value combined with serum PGI, PG II and CA199 for early gastric cancer. In the healthy group, T1W1 showed relatively uniform low signal intensity. While T2WI showed no significant increase in signal intensity. In the gastric cancer group. There was diffuse gastric wall thickening, local thickening or mass formation; T1WI and WATS showed slightly lower signal intensity in the lesion area. T2WI, FLAIR and B-TFE showed slightly uneven or moderately increased signal intensity. DWI showed limited diffusion, and the signal intensity increased uniformly or more uniformly, and the range of increase was clear. The signal intensity of MRI-DWI was 89.12 ± 8.14 in patients with low differentiation, 82.17 ± 6.35 in patients with moderate differentiation, and 74.52 ± 4.53 in patients with high differentiation. There were significant differences in the signal intensity of MRI-DWI among the three groups, and the difference was statistically significant (F=12.214, P <0.05). Serum PGI levels of subjects in the gastric cancer group were significantly lower than those in the healthy group, and the levels of PGII and CA199 were significantly higher than that in the healthy group, with statistical significance (P <0.05). The AUC, sensitivity and specificity of MRI-DWI signal intensity value and serum PGI, PGII and CA199 combined indexes in the diagnosis of gastric cancer were significantly higher than those of the independent indexes, with statistical significance (P <0.05). Conclusion: MRI-DWI signal strength value, serum PGI, PGII and CA199 levels are closely related to the occurrence and development of early gastric cancer. The combined detection and diagnosis efficiency is higher, which is helpful to improve the detection rate of early gastric cancer and is worthy of extensive clinical application.