Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain.

Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

Towards practical single-shot phase retrieval with physics-driven deep neural network.

Phase retrieval (PR), a long-established challenge for recovering a complex-valued signal from its Fourier intensity-only measurements, has attracted considerable attention due to its widespread applications in optical imaging. Recently, deep learning-based approaches were developed and allowed single-shot PR. However, due to the substantial disparity between the input and output domains of the PR problems, the performance of these approaches using vanilla deep neural networks (DNN) still has much room to improve. To increase the reconstruction accuracy, physics-informed approaches were suggested to incorporate the Fourier intensity measurements into an iterative estimation procedure. Since the approach is iterative, they require a lengthy computation process, and the accuracy is still not satisfactory for images with complex structures. Besides, many of these approaches work on simulation data that ignore some common problems such as saturation and quantization errors in practical optical PR systems. In this paper, a novel physics-driven multi-scale DNN structure dubbed PPRNet is proposed. Similar to other deep learning-based PR methods, PPRNet requires only a single Fourier intensity measurement. It is physics-driven that the network is guided to follow the Fourier intensity measurement at different scales to enhance the reconstruction accuracy. PPRNet has a feedforward structure and can be end-to-end trained. Thus, it is much faster and more accurate than the traditional physics-driven PR approaches. Extensive simulations and experiments on an optical platform were conducted. The results demonstrate the superiority and practicality of the proposed PPRNet over the traditional learning-based PR methods.

Surgical treatment of severe anterior capsular organized hard core cataract: A case report.

BACKGROUND: Complicated cataract surgery is challenging, especially in cases of hard nuclear cataract with severe anterior capsule organization. It is important to avoid the risk of surgery and improve the surgical skills of surgeons. CASE SUMMARY: A 60-year-old man presented with severe cataract and visual impairment. The anterior capsule of the lens was irregularly organized and pulled to the surrounding capsule, and white porcelain organized cord and brown-black lens nucleus were clearly visible. In phacoemulsification, maintaining the anterior capsule round and intact plays a key role in a successful surgery. In this case, if the conventional capsule treatment method was used, the anterior capsule would be torn. Therefore, we adopted a segmented anterior capsule treatment method, and a blasting method to release energy when dealing with the lens nucleus, and achieved good surgical results. CONCLUSION: Complicated cataract surgery is challenging and requires precise skills. Operation plans should be made reasonably to predict the risk of surgery, and improve the visual quality of the patients.

Effects of Post-Annealing on the Properties of ZnO:Ga Films with High Transparency (94%) and Low Sheet Resistance (29 Ω/square).

This study presents gallium-doped zinc oxide (ZnO:Ga, GZO) thin films. GZO thin films with both high transparency and low sheet resistance were prepared by RF sputtering and then post-annealed under nitrogen and hydrogen forming gas. With post-annealing at 450 °C, the proposed films with a film thickness of 100 nm showed high transparency (94%), while the sheet resistance of the films was reduced to 29 Ω/square, which was comparable with the performances of commercial indium tin oxide (ITO) samples. Post-annealing under nitrogen and hydrogen forming gas enhanced the films' conductivity while altering the thin-film composition and crystallinity. Nitrogen gas played a role in improving the crystallinity while maintaining the oxygen vacancy of the proposed films, whereas hydrogen did not dope into the thin film, thus maintaining its transparency. Furthermore, hydrogen lowered the resistance of GZO thin films during the annealing process. Then, the detailed mechanisms were discussed. Hydrogen post-annealing helped in the removal of oxygen, therefore increasing the Ga3+ content, which provided extra electrons to lower the resistivity of the films. After the preferable nitrogen/hydrogen forming gas treatment, our proposed films maintained high transparency and low sheet resistance, thus being highly useful for further opto-electronic applications.

Bone marrow immune cells respond to fluctuating nutritional stress to constrain weight regain.

Weight regain after weight loss is a major challenge in the treatment of obesity. Immune cells adapt to fluctuating nutritional stress, but their roles in regulating weight regain remain unclear. Here, we identify a stem cell-like CD7+ monocyte subpopulation accumulating in the bone marrow (BM) of mice and humans that experienced dieting-induced weight loss. Adoptive transfer of CD7+ monocytes suppresses weight regain, whereas inducible depletion of CD7+ monocytes accelerates it. These cells, accumulating metabolic memories via epigenetic adaptations, preferentially migrate to the subcutaneous white adipose tissue (WAT), where they secrete fibrinogen-like protein 2 (FGL2) to activate the protein kinase A (PKA) signaling pathway and facilitate beige fat thermogenesis. Nevertheless, CD7+ monocytes gradually enter a quiescent state after weight loss, accompanied by increased susceptibility to weight regain. Notably, administration of FMS-like tyrosine kinase 3 ligand (FLT3L) remarkably rejuvenates CD7+ monocytes, thus ameliorating rapid weight regain. Together, our findings identify a unique bone marrow-derived metabolic-memory immune cell population that could be targeted to combat obesity.

Small bowel diverticulum with enterolith causing intestinal obstruction: A case report.

BACKGROUND: Small bowel diverticula are rare in clinics, and small intestinal obstruction caused by coprolites is rarer and difficult to diagnose early. The true incidence of these diverticula may be underestimated due to their clinical symptoms not differing from those of small bowel obstruction resulting from other causes. It is common in the elderly, although it can occur at any age. CASE SUMMARY: This is a case report of a 78-year-old man with epigastric pain for 5 d. Conservative treatment does not effectively relieve pain, inflammatory indicators are elevated, and computed tomography suggests jejunal intussusception and mild ischemic changes in the intestinal wall. Laparoscopic exploration showed that the left upper abdominal loop was slightly edematous, the jejunum mass at the near Flex ligament was palpable, the size was about 7 cm × 8 cm, the local movement was slight, and the diverticulum was seen 10 cm downward, and the local small intestine was dilated and edema. Segmentectomy was performed. After the short parenteral nutrition after surgery, the fluid and enteral nutrition solution were pumped through the jejunostomy tube, and the patient was discharged after the treatment was stable, and the jejunostomy tube was removed in an outpatient clinic one month after the operation. Postoperative pathology: Jejunectomy specimen: (1) Small intestinal diverticulum with chronic inflammation, ulcer with full-thickness activity, and necrosis of the intestinal wall in some areas; (2) also see that the hard object is consistent with stone changes; and (3) the incision margin on both sides shows chronic inflammation of mucosal tissue. CONCLUSION: Clinically, the diagnosis of small bowel diverticulum is difficult to distinguish from jejunal intussusception. Combined with the patient's condition, rule out other possibilities after a timely disease diagnosis. According to the patient's body tolerance adopt personalized surgical methods to achieve better recovery after surgery.

Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

Multi-Level Resistive Al/Ga2O3/ITO Switching Devices with Interlayers of Graphene Oxide for Neuromorphic Computing.

Recently, resistive random access memory (RRAM) has been an outstanding candidate among various emerging nonvolatile memories for high-density storage and in-memory computing applications. However, traditional RRAM, which accommodates two states depending on applied voltage, cannot meet the high density requirement in the era of big data. Many research groups have demonstrated that RRAM possesses the potential for multi-level cells, which would overcome demands related to mass storage. Among numerous semiconductor materials, gallium oxide (a fourth-generation semiconductor material) is applied in the fields of optoelectronics, high-power resistive switching devices, and so on, due to its excellent transparent material properties and wide bandgap. In this study, we successfully demonstrate that Al/graphene oxide (GO)/Ga2O3/ITO RRAM has the potential to achieve two-bit storage. Compared to its single-layer counterpart, the bilayer structure has excellent electrical properties and stable reliability. The endurance characteristics could be enhanced above 100 switching cycles with an ON/OFF ratio of over 103. Moreover, the filament models are also described in this thesis to clarify the transport mechanisms.

Transcutaneous Electrical Acupoint Stimulation Improves Postoperative Sleep Quality in Patients Undergoing Laparoscopic Gastrointestinal Tumor Surgery: A Prospective, Randomized Controlled Trial.

INTRODUCTION: This study was conducted to observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the postoperative sleep quality of patients undergoing gastrointestinal tumor surgery and to verify the possible mechanism. METHODS: Eighty-three patients were allocated to the TEAS or Sham group. Patients in the TEAS group received TEAS treatment (disperse-dense waves; frequency, 2/100 Hz) on bilateral Shenmen (HT7), Neiguan (PC6) and Zusanli (ST36) points for 30 min each time, total three times in the perioperative period. In the Sham group, electrodes were placed; however, no current was given. Sleep quality was assessed on the day before surgery (P1) and the first and third days after surgery (D1 and D3) using the Pittsburgh Sleep Quality Index (PSQI) and Athens Insomnia Scale (AIS). Postoperative pain was assessed using visual analog scale (VAS) 72 h postoperatively. The incidences of abdominal distension, dizziness, postoperative nausea and vomiting (PONV) and pulmonary complications were recorded. Serum levels of inflammatory cytokines and the expression of key factors of oxidative stress and key molecules of the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signal pathway were measured. RESULTS: TEAS ameliorated sleep quality at D1 and D3 (PSQI P < 0.05, AIS P < 0.05) and decreased postoperative pain as demonstrated by lower VAS scores compared to the Sham group (P < 0.05). The incidences of abdominal distension and PONV were also lower in the TEAS group. Markers of oxidative stress were increased (P < 0.05), and the serum concentration of interleukin-6 (IL-6) was significantly lower in the TEAS group. The key mediators of the Nrf2/ARE pathway were enhanced after TEAS. CONCLUSION: Perioperative TEAS improved postoperative sleep quality, reduced postoperative pain and alleviated postoperative adverse effects in patients undergoing laparoscopic gastrointestinal tumor surgery resection. This may be associated with activating Nrf2/ARE signal pathway and decreasing its inflammatory actions. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ), ChiCTR2100054971.

Bisabolane-type sesquiterpenoids with potential anti-inflammatory and anti-HIV activities from the stems and leaves of Morinda citrifolia.

The phytochemical study on the stems and leaves of Morinda citrifolia L. resulted in the isolation of a new naturally occurring bisabolane-type sesquiterpenoid, morincitrinoid A (1), together with five known analogues (2-6). The chemical structure of 1 was elucidated by comprehensive spectral analyses. The known compounds 2-6 were identified by comparing their spectral data with those reported in the literature, which were isolated from M. citrifolia for the first time. In addition, the anti-inflammatory and anti-HIV activities of compounds 1-6 were evaluated in vitro. Compounds 1-6 displayed significant inhibitory activities on NO (nitric oxide) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells with IC50 values ranging from 0.98 ± 0.07 to 6.32 ± 0.11 µM, which was comparable to hydrocortisone. Meanwhile, compounds 1-6 showed remarkable anti-HIV-1 reverse transcriptase (RT) effects with the EC50 values ranging from 0.16 to 6.29 µM.

Resistive Switching Memory Cell Property Improvement by Al/SrZrTiO3/Al/SrZrTiO3/ITO with Embedded Al Layer.

The SrZrTiO3 (SZT) thin film prepared by sol-gel process for the insulator of resistive random-access memory (RRAM) is presented. Al was embedded in the SZT thin film to enhance the switching characteristics. Compared with the pure SZT thin-film RRAM, the RRAM with the embedded Al in SZT thin film demonstrated outstanding device parameter improvements, such as a resistance ratio higher than 107, lower operation voltage (VSET = -0.8 V and VRESET = 2.05 V), uniform film, and device stability of more than 105 s. The physical properties of the SZT thin film and the embedded-Al SZT thin-film RRAM devices were probed.

SiSPRNet: end-to-end learning for single-shot phase retrieval.

With the success of deep learning methods in many image processing tasks, deep learning approaches have also been introduced to the phase retrieval problem recently. These approaches are different from the traditional iterative optimization methods in that they usually require only one intensity measurement and can reconstruct phase images in real-time. However, because of tremendous domain discrepancy, the quality of the reconstructed images given by these approaches still has much room to improve to meet the general application requirements. In this paper, we design a novel deep neural network structure named SiSPRNet for phase retrieval based on a single Fourier intensity measurement. To effectively utilize the spectral information of the measurements, we propose a new feature extraction unit using the Multi-Layer Perceptron (MLP) as the front end. It allows all pixels of the input intensity image to be considered together for exploring their global representation. The size of the MLP is carefully designed to facilitate the extraction of the representative features while reducing noises and outliers. A dropout layer is also equipped to mitigate the possible overfitting problem in training the MLP. To promote the global correlation in the reconstructed images, a self-attention mechanism is introduced to the Up-sampling and Reconstruction (UR) blocks of the proposed SiSPRNet. These UR blocks are inserted into a residual learning structure to prevent the weak information flow and vanishing gradient problems due to their complex layer structure. Extensive evaluations of the proposed model are performed using different testing datasets of phase-only images and images with linearly related magnitude and phase. Experiments were conducted on an optical experimentation platform (with defocusing to reduce the saturation problem) to understand the performance of different deep learning methods when working in a practical environment. The results demonstrate that the proposed approach consistently outperforms other deep learning methods in single-shot maskless phase retrieval. The source codes of the proposed method have been released in Github [see references].

High Linearity Synaptic Devices Using Ar Plasma Treatment on HfO2 Thin Film with Non-Identical Pulse Waveforms.

We enhanced the device uniformity for reliable memory performances by increasing the device surface roughness by exposing the HfO2 thin film surface to argon (Ar) plasma. The results showed significant improvements in electrical and synaptic properties, including memory window, linearity, pattern recognition accuracy, and synaptic weight modulations. Furthermore, we proposed a non-identical pulse waveform for further improvement in linearity accuracy. From the simulation results, the Ar plasma processing device using the designed waveform as the input signals significantly improved the off-chip training and inference accuracy, achieving 96.3% training accuracy and 97.1% inference accuracy in only 10 training cycles.

Experimental and Numerical Analysis on the Impact Wear Behavior of TP316H Steel.

In this work, the contact force model and experiment methods were used to study the dynamic response and impact wear behavior of TP316H steel. The Flore model and the classic Hertz model were selected for comparison with the experimental results, and the model was revised according to the section parameters of the TP316H tube. The results show that there is a large difference between the models without considering the effect of structural stiffness on the impact system and the test results, whereas the revised model has a good agreement. With the rise in impact mass, the coefficient of restitution increases from 0.65 to 0.78, whereas the energy dissipation and wear volume decrease. Spalling, delamination, plastic deformation, and oxidative wear are the main impact wear mechanism of TP316H steel.

CD38+ B cells affect immunotherapy for allergic rhinitis.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the mainstay in the treatment of allergic diseases, but the therapeutic effects of AIT need to be improved. CD38+ B cells are an immune cell fraction involved in the pathogenesis of allergic diseases as well as in immune regulation. OBJECTIVE: We sought to elucidate the role of antigen-specific CD38+ B cells in AIT. METHODS: An analysis was carried out on AIT results of 48 patients with perennial allergic rhinitis (AR), among which peripheral blood immune cells were analyzed by flow cytometry; serum cytokine levels were determined by ELISA. An AR murine model was developed to test the role of CD38+ B cells in AIT. RESULTS: A fraction of antigen-specific CD38+ B cell was detected in AR patients. CD38+ B-cell frequency was negatively correlated with the therapeutic effects of AIT. A negative correlation was detected between the CD38+ B-cell frequency and regulatory T-cell frequency in AR patients treated with AIT. Exposure to specific antigens induced CD38+ B cells to produce IL-6, that converted Treg cells to TH17 cells. Coadministration of anti-CD38 antibody significantly promoted the therapeutic effects of AIT. CONCLUSIONS: Antigen-specific CD38+ B cells compromise AIT effects by producing IL-6 to convert regulatory T cells to TH17 cells. Inhibition of CD38+ B cells promotes the effects of AIT.

Condition notification assisted by virtual reality technology reduces the anxiety levels of parents of children with simple CHD: a prospective randomised controlled study.

PURPOSE: This study explored the effects of condition notification based on virtual reality technology on the anxiety levels of parents of children with simple CHD. METHODS: The subjects of the study were the parents of 60 children with simple CHD who were treated in our centre. The state anxiety scale was used to assess the anxiety status of the parents of the children before and after the condition notification in different ways (based on virtual reality explanations and written explanations). RESULTS: In this study, a total of 55 parents of children with CHD successfully completed the survey. At the time of admission, there was no significant difference in the state anxiety scale scores of the parents between the two groups. The anxiety status of the virtual reality group was relieved after the condition notification assisted by virtual reality technology, and there was a significant difference compared with the control group. CONCLUSION: Condition notification based on virtual reality technology can effectively alleviate the anxiety of parents of children with simple CHD, which is worthy of clinical application.

FGF9 promotes cell proliferation and tumorigenesis in TM3 mouse Leydig progenitor cells.

Fibroblast growth factor 9 (FGF9) modulates cell proliferation, differentiation and motility for development and tissue repair in normal cells. Growing evidence shows that abnormal activation of FGF9 signaling is associated with tumor malignancy. We have previously reported that FGF9 increases MA-10 mouse Leydig tumor cell proliferation, in vitro, and tumor growth, in vivo. Also, FGF9 promotes the tumor growth and liver metastasis of mouse Lewis lung cancer cells, in vivo. However, the effects of FGF9 in the early stage of tumorigenesis remains elusive. In this study, TM3 mouse Leydig progenitor cells, that are not tumorigenic in immunocompromised mice, were used as a model cell line to investigate the role of FGF9 in tumorigenesis. The results demonstrated that FGF9 significantly induced cell proliferation and activated the MAPK, PI3K and PLCγ signaling pathways in TM3 cells. The percentage of the cell number in G1 phase was reduced and that in S and G2/M phases was increased after FGF9 stimulation in TM3 cells. Cyclin D1, cyclin A1, CDK2, CDK1, and p21 expressions and the phosphorylation level of Rb were all induced in FGF9-treated TM3 cells. In addition, FGF9 increased the expression of FGF receptor 1-4 in TM3 cells, suggesting the positive feedback loop between FGF9 and FGFRs. Furthermore, in the allograft mouse model, FGF9 promoted the tumorigenesis of TM3 cells characterized by higher expression of tumor markers, such as tumor necrosis factor alpha (TNFα) and α-fetoprotein (AFP), in the subcutaneously inoculated TM3 cell tissue. Conclusively, FGF9 induced cell cycle to increase cell proliferation of TM3 cells through FAK, MAPK, PI3K/Akt and PLCγ signaling pathways, in vitro, and promoted the tumorigenesis of TM3 cell allograft tissue, in vivo, which is a potential marker for tumor as well as a target for cancer therapeutic strategies.

Effect of the Addition of Human Milk Fortifier to Breast Milk on the Early Recovery of Infants After Congenital Cardiac Surgery.

Objective: This article studied the effect of breast milk supplemented with human milk fortifier (HMF) on the early recovery of infants after congenital cardiac surgery. Methods: Infants undergoing congenital cardiac surgery were randomly divided into an intervention group (n = 27) and a control group (n = 27). Infants in the intervention group received HMF, and those in the control group were exclusively breastfed. The nutritional indicators at discharge, the postoperative recovery status, and nutritional-related complications were recorded. Results: Compared with the control group at the time of discharge, the weight and albumin and prealbumin levels of the intervention group were significantly increased (P < 0.05). The length of hospital stay of the intervention group was significantly reduced compared with that of the control group (P < 0.05). Although the length of ICU stay for the intervention group was shorter than that of the control group, the difference was not significant (P > 0.05). No significant difference in the incidence of postoperative nutrition-related complications was noted between the two groups (P > 0.05). Conclusion: Compared with breastfeeding alone, with HMF can improve postoperative weight gains, reduce the length of stay, and promote infants' early recovery after congenital cardiac surgery.

The effect of early oral stimulation with breast milk on the feeding behavior of infants after congenital cardiac surgery.

OBJECTIVE: To investigate the effect of early oral stimulation with breast milk on the feeding behavior of infants after congenital cardiac surgery. METHODS: Infants with congenital heart disease were randomly divided into the breast milk oral stimulation group (n = 23), physiological saline oral stimulation group (n = 23) and control group (n = 23). Debra Beckman's oral exercise program was used with breast milk and physiological saline in the breast milk oral stimulation group and the physiological saline oral stimulation group, respectively. The time oral feeding and total oral nutrition were started, the length of intensive care unit (ICU) stay and hospital stay, weight and the complications at discharge were recorded for each group and statistically analyzed. RESULTS: The time oral feeding and total oral nutrition were started and the length of ICU stay and hospital stay were significantly less in the breast milk oral stimulation group and physiological saline oral stimulation group than in the control group (P < 0.05). There were no significant differences in other indicators between the breast milk oral stimulation group and the physiological saline oral stimulation group, except for the time total oral nutrition began (P < 0.05). However, there were no significant differences in weight or complications at discharge among the three groups (P > 0.05). CONCLUSION: Early oral stimulation exercises with breast milk can help infant patients quickly recover total oral nutrition and reduce the length of ICU and hospital stay after cardiac surgery.