R2D2-GAN: Robust Dual Discriminator Generative Adversarial Network for Microscopy Hyperspectral Image Super-Resolution.

High-resolution microscopy hyperspectral (HS) images can provide highly detailed spatial and spectral information, enabling the identification and analysis of biological tissues at a microscale level. Recently, significant efforts have been devoted to enhancing the resolution of HS images by leveraging high spatial resolution multispectral (MS) images. However, the inherent hardware constraints lead to a significant distribution gap between HS and MS images, posing challenges for image super-resolution within biomedical domains. This discrepancy may arise from various factors, including variations in camera imaging principles (e.g., snapshot and push-broom imaging), shooting positions, and the presence of noise interference. To address these challenges, we introduced a unique unsupervised super-resolution framework named R2D2-GAN. This framework utilizes a generative adversarial network (GAN) to efficiently merge the two data modalities and improve the resolution of microscopy HS images. Traditionally, supervised approaches have relied on intuitive and sensitive loss functions, such as mean squared error (MSE). Our method, trained in a real-world unsupervised setting, benefits from exploiting consistent information across the two modalities. It employs a game-theoretic strategy and dynamic adversarial loss, rather than relying solely on fixed training strategies for reconstruction loss. Furthermore, we have augmented our proposed model with a central consistency regularization (CCR) module, aiming to further enhance the robustness of the R2D2-GAN. Our experimental results show that the proposed method is accurate and robust for super-resolution images. We specifically tested our proposed method on both a real and a synthetic dataset, obtaining promising results in comparison to other state-of-the-art methods. Our code and datasets are accessible through Multimedia Content.

Association of preoperative and postoperative circulating tumour DNA (ctDNA) with PIK3CA gene mutation with risk of recurrence in patients with non-metastatic breast cancer.

BACKGROUND: Circulating tumour DNA (ctDNA), contains tumour-specific gene mutation in blood circulation and could aid in postoperative risk stratification of non-metastatic breast cancer. In this study, we investigated the feasibility of detecting PIK3CA gene mutations in ctDNA in the preoperative (preop) and postoperative period (postop), and its prognostic significance in patients with breast cancer. METHODS: A cohort of patients with breast cancer undergoing curative surgery with available blood samples preoperatively and postoperatively (Post op) at either Post op time period; week 1-2, week 3-4 or weeks 5-12 were enrolled. PIK3CA gene mutations at exons 9 and 20 were detected in ctDNA with High resolution melting (HRM) PCR and Allele specific fluorescence probe-based PCR. RESULTS: A total of 62 patients (age, median (IQR), 51.50 (45.0-65.0) years), with a median follow-up of 90 months (interquartile range (IQR),60-120 months) were enrolled. In total, 25 (40.3%) and 22 (35%) patients with breast cancer had detectable PIK3CA gene mutations in ctDNA in preoperative and postoperative period, respectively. PIK3CA gene mutations in ctDNA in postoperative period (hazard ratio (H.R: 18.05, p = 0.001) were a negative prognostic factor for recurrencefree survival (RFS) and overall survival (OS) (H.R: 11.9, p = 0.01) in patients with breast cancer. Subgroup analysis of ctDNA indicate that positive ctDNA in both preoperative/postoperative period and post op period only were found to have prognostic effect on RFS and OS (RFS; p < 0.0001, O·S; p = 0.0007). Moreover, ctDNA-based detection preceded clinical detection of recurrence in patients with an average lead time of 12 months (IQR:20-28.5 months) across all the breast cancer subtypes. CONCLUSION: We highlighted the prognostic ability of ctDNA in patients with breast cancer in perioperative period. However, future prospective studies are needed to assess the utility of ctDNA in clinical practice.

Endothelial glycocalyx injury is involved in heatstroke-associated coagulopathy and protected by N-acetylcysteine.

Introduction: Damage to endothelial glycocalyx (EGCX) can lead to coagulation disorders in sepsis. Heat stroke (HS) resembles sepsis in many aspects; however, it is unclear whether EGCX injury is involved in its pathophysiology. The purpose of this study was to examine the relationship between the damage of EGCX and the development of coagulation disorders during HS. Methods: We retrospectively collected 159 HS patients and analyzed coagulation characteristics and prognosis of HS patients with or without disseminated intravascular coagulation (DIC). We also replicated a rat HS model and measured coagulation indexes, pulmonary capillary EGCX injury in HS rats. Finally, we evaluated the effect of the antioxidant N-acetylcysteine (NAC) on HS-initiated EGCX injury and coagulation disorders. Results: Clinical data showed that HS patients complicated with DIC had a higher risk of death than HS patients without DIC. In a rat HS model, we found that rats subjected to heat stress developed hypercoagulability and platelet activation at the core body temperature of 43°C, just before the onset of HS. At 24 h of HS, the rats showed a consumptive hypo-coagulation state. The pulmonary capillary EGCX started to shed at 0 h of HS and became more severe at 24 h of HS. Importantly, pretreatment with NAC substantially alleviated EGCX damage and reversed the hypo-coagulation state in HS rats. Mechanically, HS initiated reactive oxidative species (ROS) generation, while ROS could directly cause EGCX damage. Critically, NAC protected against EGCX injury by attenuating ROS production in heat-stressed or hydrogen peroxide (H2O2)-stimulated endothelial cells. Discussion: Our results indicate that the poor prognosis of HS patients correlates with severe coagulation disorders, coagulation abnormalities in HS rats are associated with the damage of EGCX, and NAC improves HS-induced coagulopathy, probably through its protection against EGCX injury by preventing ROS generation.

A 1.1 Mb duplication CNV on chromosome 17 contributes to skeletal muscle development in Boer goats.

The Boer goat is one of the top meat breeds in modern animal husbandry and has attracted widespread attention for its unique growth performance. However, the genetic basis of muscle development in the Boer goat remains obscure. In this study, we identified specific structural variants in the Boer goat based on genome-wide selection signals and analyzed the basis of the molecular heredity of related candidate genes in muscle development. A total of 9 959 autosomal copy number variations (CNVs) were identified through selection signal analysis in 127 goat genomes. Specifically, we confirmed that the highest signal CNV (HSV) was a chromosomal arrangement containing an approximately 1.11 Mb (CHIR17: 60062304-61171840 bp) duplicated fragment inserted in reverse orientation and a 5 362 bp deleted region (CHIR17:60145940-60151302 bp) with overlapping genes (e.g., ARHGAP10, NR3C2, EDNRA, PRMT9, and TMEM184C). The homozygous duplicated HSV genotype (+/+) was found in 96% of Boer goats but was not detected in Eurasian goats and was only detected in 4% of indigenous African goats. The expression network of three candidate genes ( ARHGAP10, NR3C2, and EDNRA) regulating dose transcription was constructed by RNA sequencing. Results indicated that these genes were involved in the proliferation and differentiation of skeletal muscle satellite cells (SMSCs) and their overexpression significantly increased the expression of SAA3. The HSV of the Boer goat contributed to superior skeletal muscle growth via the dose effects of overlapping genes.

Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression.

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis. To provide clinical practice recommendations on the immune function in sepsis, an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed. Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed, Web of Science, and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire. Then, the Delphi method was used to form consensus opinions, and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions. This consensus achieved satisfactory results through two rounds of questionnaire survey, with 2 statements rated as perfect consistency, 13 as very good consistency, and 9 as good consistency. After summarizing the results, a total of 14 strong recommended opinions, 8 weak recommended opinions and 2 non-recommended opinions were produced. Finally, a face-to-face discussion of the consensus opinions was performed through an online meeting, and all judges unanimously agreed on the content of this consensus. In summary, this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

Induction of Trained Immunity Protects Neonatal Mice Against Microbial Sepsis by Boosting Both the Inflammatory Response and Antimicrobial Activity.

Background: Neonates are susceptible to a wide range of microbial infection and at a high risk to develop severe sepsis and septic shock. Emerged evidence has shown that induction of trained immunity triggers a much stronger inflammatory response in adult monocytes/macrophages, thereby conferring protection against microbial infection. Methods: This study was carried out to examine whether trained immunity is inducible and exerts its protection against microbial sepsis in neonates. Results: Induction of trained immunity by Bacillus Calmette-Guerin (BCG) plus bacterial lipoprotein (BLP) protected neonatal mice against cecal slurry peritonitis-induced polymicrobial sepsis, and this protection is associated with elevated circulating inflammatory cytokines, increased neutrophil recruitment, and accelerated bacterial clearance. In vitro stimulation of neonatal murine macrophages with BCG+BLP augmented both inflammatory response and antimicrobial activity. Notably, BCG+BLP stimulation resulted in epigenetic remodeling characterized by histone modifications with enhanced H3K4me3, H3K27Ac, and suppressed H3K9me3 at the promoters of the targeted inflammatory and antimicrobial genes. Critically, BCG+BLP stimulation led to a shift in cellular metabolism with increased glycolysis, which is the prerequisite for subsequent BCG+BLP-triggered epigenetic reprogramming and augmented inflammatory response and antimicrobial capacity. Conclusion: These results illustrate that BCG+BLP induces trained immunity in neonates, thereby protecting against microbial infection by boosting both inflammatory and antimicrobial responses.

Effects of HIF-1α, hepcidin and PTH on RankL in patients with chronic kidney disease in different stages.

OBJECTIVE: To investigate the effects of hypoxia-inducible factor-1α (HIF-1α), hepcidin, and parathyroid hormone (PTH) on the serum nuclear factor κB and receptor activating factor ligand (RankL) in patients with chronic kidney disease (CKD) stages 3-5. METHODS: A total of 90 patients admitted to our hospital's Department of Nephrology from March 2018 to December 2019 were randomly selected as the subjects (30 patients with CKD3, CKD4, and CKD5 each). A total of 30 healthy volunteers receiving a physical examination in our hospital during the same period were selected for the control group. Then, the participants' HIF-1α, hepcidin, and RankL levels were detected by double-antibody sandwiched enzyme-linked immunosorbent assay. The serum creatinine, serum iron, hemoglobin, and phosphorus (P3+) levels were determined by BeckMAN-c800 automatic biochemical analysis. The glomerular filtration rate (eGFR) was calculated by the CKD-EPI formula. RESULTS: (1) The levels of HIF-1α, RankL, hepcidin, and PTH were all elevated, and the serum ferritin and P3+ were elevated in each stage; (2) Linear correlation analysis: The HIF-1α and hepcidin showed a higher correlation with RankL in CKD3 and CKD4(CKD3: The correlation coefficient r = 0.558 between HIF-1α and RankL, and r = 0.604 between HEpcidin and RankL; CKD4: Correlation coefficient r = 0.840 between HIF-1α and RankL, and r = 0.753 between HEpcidin and RankL), while the PTH showed a higher correlation with RankL in CKD5 (correlation index r = 0.631). Multiple linear stepwise regression analysis: RankL was independently correlated with HIF-1α, hepcidin, and PTH. Regression coefficient B of HIF-1α was the highest in both CKD3 and CKD4. The coefficient B value of PTH in CKD5 was 3.971; HIF-1α and hepcidin were not included in the regression equation. CONCLUSION: The levels of RankL in both CKD3 and CKD4 were increased and mainly affected by HIF-1α, followed by hepcidin. Moreover, HIF-1α and PTH had a combined effect on the RankL level in CKD5, and PTH was the main influencing factor.

Ion/Electron Redistributed 3D Flexible Host for Achieving Highly Reversible Li Metal Batteries.

3D carbon frameworks are promising hosts to achieve highly reversible lithium (Li) metal anodes, whereas insufficient effects are attributed to their single electron conductivity causing local aggregating of electron/Li+ and uncontrollable Li dendrites. Herein, an ion/electron redistributed 3D flexible host is designed by lithiophilic carbon fiber cloth (CFC) modified with metal-organic framework (MOF)-derived porous carbon sheath with embedded CoP nanoparticles (CoP-C@CFC). Theory calculations demonstrate the strong binding energy and plenty of charge transfer from the reaction between CoP and Li atom are presented, which is beneficial to in situ construct a Li3 P@Co ion/electron conductive interface on every single CoP-C@CFC. Thanks to the high ionic conductive Li3 P and electron-conductive Co nanoparticles, the rapid dispersion of Li+ and obviously reduced local current density can be achieved simultaneously. Furthermore, in situ optical microscopy observations display obvious depression for volume expansion and Li dendrites. As expected, a miraculous average Coulombic efficiency (CE) of 99.96% over 1100 cycles at 3 mA cm-2 and a low overpotential of 11.5 mV with prolonged cycling of over 3200 h at 20% depth of discharge are successfully obtained. Consequently, the CoP-C@CFC-Li||LiFePO4 full cells maintain a capacity retention of 95.8% with high CE of 99.96% over 500 cycles at 2 C and excellent rate capability.

Exosomes from M2 macrophages promoted glycolysis in FaDu cells by inhibiting PDLIM2 expression to stabilize PFKL.

Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent malignant diseases worldwide. LSCC patients suffer from a severe decline in life quality, due to the essential roles of the larynx in basic functions in the human body. The overarching goal of the present study is to explore whether exosome from M2 macrophages promotes LSCC by targeting glycolysis. In the current study, the expression of PDLIM2, an E3 ubiquitin ligase, in clinical samples was monitored by quantitative PCR and immunohistochemical examination. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by the Seahorse machine. Cell proliferation was measured by using Cell Counting Kit-8. A luciferase assay was performed to verify the regulation of miRNA on its target gene. The results showed that PDLIM2 exhibited downregulation in LSCC clinical samples and was associated with stage and differentiation of tumors in patients. In FaDu cell line, PDLIM2 inhibited cell proliferation and glycolysis but promoted the ubiquitination of PFKL. Exosomes from M2-type macrophages delivered miR-222-3p into LSCC cells to suppress PDLIM2 expression, leading to the elevated expression of PFKL and enhanced glycolysis which accelerated the proliferation of FaDu cells. The findings from cultured cells were supported by a subcutaneous tumor growth model in nude mice. Collectively, our data provided a snapshot of the miR-222-3p/PDLIM2/PFKL axis in LSCC tumorigenesis, and in concert with the importance of TAM exosomes and glycolysis, could be potentially translated to LSCC clinics.

Autophagy induced by taurolidine protects against polymicrobial sepsis by promoting both host resistance and disease tolerance.

Sepsis, septic shock, and their sequelae are the leading causes of death in intensive care units, with limited therapeutic options. Disease resistance and tolerance are two evolutionarily conserved yet distinct defense strategies that protect the host against microbial infection. Here, we report that taurolidine administered at 6 h before septic challenge led to strong protection against polymicrobial sepsis by promoting both host resistance and disease tolerance characterized by accelerated bacterial clearance, ameliorated organ damage, and diminished vascular and gut permeability. Notably, taurolidine administered at 6 h after septic challenge also rescued mice from sepsis-associated lethality by enhancing disease tolerance to tissue and organ injury. Importantly, this in vivo protection afforded by taurolidine depends on an intact autophagy pathway, as taurolidine protected wild-type mice but was unable to rescue autophagy-deficient mice from microbial sepsis. In vitro, taurolidine induced light chain 3-associated phagocytosis in innate phagocytes and autophagy in vascular endothelium and gut epithelium, resulting in augmented bactericidal activity and enhanced cellular tolerance to endotoxin-induced damage in these cells. These results illustrate that taurolidine-induced autophagy augments both host resistance and disease tolerance to bacterial infection, thereby conferring protection against microbial sepsis.

Assessment of cell-free DNA (cfDNA) concentrations in the perioperative period can predict risk of recurrence in patients with non-metastatic breast cancer.

BACKGROUND: Circulating cell-free DNA (cfDNA) is a potential non-invasive biomarker of disease status in patients with cancer, and provides important diagnostic and prognostic information in breast cancer. The goal of this study was to quantify cfDNA concentrations during the perioperative period and investigate its potential utility to detect recurrence outcomes in patients with breast cancer. METHODS: Sixty-two (n = 62) patients with non-metastatic breast cancer, undergoing curative-intent surgery were screened for inclusion. Blood samples were collected from these patients: pre-operatively (Preop) and post-operatively (PO) at either of the following PO time points; PO week 1-2, PO week 3-4 and PO weeks 5-12 following surgery. cfDNA was extracted and quantified using nanodrop spectrophotometer. RESULTS: In a cohort of 62 patients (age, median (IQR), 51.5(45.0-65.0) years), with a median follow-up of 90 months (interquartile range (IQR),60-120 months), significant association was observed between cfDNA concentrations and risk of recurrence in patients with breast cancer. The group of patients who had disease recurrence during follow-up had significantly higher cfDNA concentrations (cutoff:400 ng/ml) compared to the group of patients who remain disease-free (Preop and PO period: p < 0.0001). The median Recurrence Free Survival (RFS) between the Disease Recurrence (DR) and the Disease Free (DF) groups of patients with breast cancer were 12(20-28.5) months and 72.00 (96-120) months; p < 0.0001). Univariate and multivariate cox regression analysis indicated that postoperative cfDNA concentration (Hazard ratio:5.0, 95% Confidence Interval:1.19-21.28, p = 0.028) was an independent negative prognostic factor for RFS in patients with non-metastatic breast cancer. CONCLUSION: Our study demonstrated that high postoperative cfDNA is associated with increased risk of future recurrence in patients with non-metastatic breast cancer. Further, prospective studies are warranted to validate its clinical utility in breast cancer.

The utility of plasma circulating cell-free messenger RNA as a biomarker of glioma: a pilot study.

BACKGROUND: Research into the potential utility of plasma-derived circulating cell-free nucleic acids as non-invasive adjuncts to radiological imaging have been occasioned by the invasive nature of brain tumour biopsy. The objective of this study was to determine whether significant differences exist in the plasma transcriptomic profile of glioma patients relative to differences in their tumour characteristics, and also whether any observed differences were representative of synchronously obtained glioma samples and TCGA glioma-derived RNA. METHODS: Blood samples were collected from twenty glioma patients prior to tumour resection. Plasma ccfmRNAs and glioma-derived RNA were extracted and profiled. RESULTS: BCL2L1, GZMB, HLA-A, IRF1, MYD88, TLR2, and TP53 genes were significantly over-expressed in glioma patients (p < 0.001, versus control). GZMB and HLA-A genes were significantly over-expressed in high-grade glioma patients (p < 0.001, versus low-grade glioma patients). Moreover, the fold change of the BCL2L1 gene was observed to be higher in patients with high-grade glioma (p = 0.022, versus low-grade glioma patients). There was positive correlation between the magnitude of fold change of differentially expressed genes in plasma- and glioma-derived RNA (Spearman r = 0.6344, n = 14, p = 0.017), and with the mean FPKM in TCGA glioma-derived RNA samples (Spearman r = 0.4614, n = 19, p < 0.05). There was positive correlation between glioma radiographic tumour burden and the magnitude of fold change of the CSF3 gene (r = 0.9813, n = 20, p < 0.001). CONCLUSION: We identified significant differential expression of genes involved in cancer inflammation and immunity crosstalk among patients with different glioma grades, and there was positive correlation between their transcriptomic profile in plasma and tumour samples, and with TCGA glioma-derived RNA.

Plasma circulating cell free messenger RNA as a potential biomarker of melanoma.

BACKGROUND: Blood borne cell free nucleic acids are increasingly emerging as significant non-invasive adjuncts to current methods of disease status evaluation in cancer patients. In this study, we sought to examine whether significant differences exist in the plasma transcriptomic profile of advanced melanoma patients with a high disease burden compared to patients with a low disease burden or therapeutic response. METHODS: Pathway focussed gene expression analysis was performed using cDNA derived from the plasma circulating cell free messenger ribonucleic acid (ccfmRNA) samples of twenty-two patients with advanced melanoma. Patients were assessed with paired blood sample collection and CT scan assessments at baseline and at 3 months follow up. RESULTS: We identified several genes which were significantly over-expressed in patients with a low disease burden or therapeutic response; BCL2L1, CXCL9, IDO1, IL13, MIF, MYD88 and TLR4 (p ≤ 0.001, versus high disease burden). There was an increase in the magnitude of fold change (2^ (-dd CT)) of BCL2L1 (p = 0.031), CCL4 (p = 0.001), CCL5 (p = 0.043), CXCL9 (p = 0.012), GZMB (p = 0.023) and TNFSF10 (p = 0.039) genes in patients with therapeutic response at 3 months follow up assessment relative to baseline assessment. Moreover, in stage IV melanoma patients with brain metastases, CCL18, CCR1, CCR4, CD274, CSF2, EGF, and PTGS2 genes were significantly over-expressed (p < 0.001, versus patients without melanoma brain metastasis). CONCLUSION: Significant differences were observed in the plasma transcriptomic profile between the various melanoma patient groups, and we postulate that these differences may be exploited to identify novel therapeutic targets or biomarkers relevant to melanoma.

Association Cortex Is Essential to Reverse Hemianopia by Multisensory Training.

Hemianopia induced by unilateral visual cortex lesions can be resolved by repeatedly exposing the blinded hemifield to auditory-visual stimuli. This rehabilitative "training" paradigm depends on mechanisms of multisensory plasticity that restore the lost visual responsiveness of multisensory neurons in the ipsilesional superior colliculus (SC) so that they can once again support vision in the blinded hemifield. These changes are thought to operate via the convergent visual and auditory signals relayed to the SC from association cortex (the anterior ectosylvian sulcus [AES], in cat). The present study tested this assumption by cryogenically deactivating ipsilesional AES in hemianopic, anesthetized cats during weekly multisensory training sessions. No signs of visual recovery were evident in this condition, even after providing animals with up to twice the number of training sessions required for effective rehabilitation. Subsequent training under the same conditions, but with AES active, reversed the hemianopia within the normal timeframe. These results indicate that the corticotectal circuit that is normally engaged in SC multisensory plasticity has to be operational for the brain to use visual-auditory experience to resolve hemianopia.

Evaluation of the Cytotoxic Effects of the Novel Antineoplastic Agent 1,4,5-Oxathiazinane-4,4-dioxide on Triple Negative Breast Cancer Cells.

BACKGROUND/AIM: Adjuvant therapeutic options are limited for triple negative breast cancer (TNBC). Thus, we evaluated the cytotoxic effects of the newly synthesized antineoplastic agent 1,4,5-Oxathiazinane-4,4-dioxide (OTD) on TNBC cells as a potential cancer therapeutic strategy. MATERIALS AND METHODS: TNBC primary BT-20 and metastatic MDA-MB-231 cell lines were treated with increasing concentrations of OTD for various time periods to assess cell viability. Cell necrosis, apoptosis, necroptosis, autophagy, and ROS generation were evaluated using assay kits or specific inhibitors. RESULTS: Treatment with OTD resulted in a dose- and time-dependent cell death of TNBC BT-20 and MDA-MB-231 cells. OTD also dose-dependently arrested TNBC cell proliferation. Notably, treatment with OTD induced both necrosis and apoptosis of TNBC cells, while the pan-caspase inhibitor Z-VAD-FMK partially attenuated OTD-induced cell death. Importantly, abrogated OTD-induced cell death was observed in the presence of the ROS scavenger N-acetylcysteine (NAC), whereas enhanced OTD-induced cell death was observed after the addition of the glutathione synthesis inhibitor BSO, indicating OTD-induced killing of TNBC cells via a reactive oxygen species-dependent mechanism. CONCLUSION: OTD is strongly cytotoxic to both primary and metastatic TNBC cells, possibly by inducing multiple cell death pathways.

A 3D-mixed ion/electron conducting scaffold prepared by in situ conversion for long-life lithium metal anodes.

Lithium (Li) metal is widely considered the most promising anode material because of its ultrahigh specific energy. However, the obvious volume change and uncontrollable dendrite growth hinder its commercial applications. Herein, we designed a 3D scaffold of Cu3P nanoarray-modified Cu foam via in situ conversion (3D MIECS). Uniform lithiophilic Cu3P nanoarrays were in situ grown inside the Cu foam (Cu3P NA@CF) that presented a high specific surface area and very low nucleation overpotential. Specifically, the lithiated Cu3P nanoarrays possess the features of mixed ion/electron conductivity and structural stability responsible for uniform Li deposition in the whole three-dimensional space of the metal skeleton, showing scarcely any volume expansion or structural collapse during the continuous Li plating/stripping process. Therefore, the modified Cu foam host achieves dendrite-free cycling over 600 cycles at a current density of 3 mA cm-2 with a coulombic efficiency (CE) of 99.1%. A 3D MIECS-Li||LiFePO4 full cell holds a capacity retention of 80% with a stable CE of 99.63% over 1000 cycles at 3 C.

Dl-3-n-butylphthalide attenuates hypoxic-ischemic brain injury through inhibiting endoplasmic reticulum stress-induced cell apoptosis and alleviating blood-brain barrier disruption in newborn rats.

Dl-3-n-butylphthalide (NBP) has been demonstrated to exert neuroprotective effects in experimental models and human patients. This study was performed to assess the therapeutic effects and the underlying molecular mechanisms of NBP in a neonatal hypoxic-ischemic rat model. The results showed that NBP treatment significantly reduced the infarct volume, improved histological recovery, decreased neuronal cell loss, enhanced neuronal cell rehabilitation, promoted neurite growth and decreased white matter injury. In addition, NBP treatment effectively improved long-term neurobehavioral development and prognosis after HI injury. We further demonstrated an inhibitory effect of NBP on endoplasmic reticulum (ER) stress-induced apoptosis, evidenced by reduction in ER stress-related protein expressions (GRP78, XBP-1, PDI and CHOP), decrease in TUNEL-positive cells, down-regulation in pro-apoptosis protein (Bax and cleaved caspase-3), up-regulation in anti-apoptosis protein (Bcl-2). Moreover, NBP exerted a protective effect in blood-brain barrier disruption, which ameliorated brain edema and reduced the degeneration of the tight junction proteins (Occludin and Claudin-5) and adherens junction proteins (P120-Catenin, VE-Cadherin and ß-Catenin). Overall, our findings demonstrated that NBP treatment attenuated HI brain injury through inhibiting ER stress-induced apoptosis and alleviating blood-brain barrier disruption in newborn rats. This work provides an effective therapeutic strategy to reduce brain damage and enhance recovery after neonatal HI brain injury.

Protective effects of FGF10 on neurovascular unit in a rat model of neonatal hypoxic-ischemic brain injury.

Neonatal hypoxic-ischemic (HI) brain injury remains a devastating clinical disease associated with high mortality and lifetime disability. Neonatal HI injury damages the architecture of neurovascular unit (NVU), thus, therapy targeting the NVU may provide effective neuroprotection against HI. This study was designed to investigate whether fibroblast growth factor 10 (FGF10) protected the NVU against HI and afforded observable neuroprotection in a rat model of neonatal HI brain injury. The results showed that FGF10 treatment significantly reduced brain damage post HI, characterized by reduction in brain infarct volume and tissue loss. Further interesting findings showed that FGF10 treatment exerted neuroprotective effects on HI brain injury in neonate rats through protecting the NVU against HI, evidenced by inhibition of neuronal cell apoptosis, suppression of gliosis, and amelioration of blood-brain barrier disruption. Collectively, our study indicates that FGF10 treatment exhibits great potential for protecting NVU against HI and attenuates neonatal brain injury, suggesting a potential novel therapeutic agent to this disease.

Reversing Hemianopia by Multisensory Training Under Anesthesia.

Hemianopia is characterized by blindness in one half of the visual field and is a common consequence of stroke and unilateral injury to the visual cortex. There are few effective rehabilitative strategies that can relieve it. Using the cat as an animal model of hemianopia, we found that blindness induced by lesions targeting all contiguous areas of the visual cortex could be rapidly reversed by a non-invasive, multisensory (auditory-visual) exposure procedure even while animals were anesthetized. Surprisingly few trials were required to reinstate vision in the previously blind hemisphere. That rehabilitation was possible under anesthesia indicates that the visuomotor behaviors commonly believed to be essential are not required for this recovery, nor are factors such as attention, motivation, reward, or the various other cognitive features that are generally thought to facilitate neuro-rehabilitative therapies.