Deep learning-based point-scanning super-resolution imaging.

Point-scanning imaging systems are among the most widely used tools for high-resolution cellular and tissue imaging, benefiting from arbitrarily defined pixel sizes. The resolution, speed, sample preservation and signal-to-noise ratio (SNR) of point-scanning systems are difficult to optimize simultaneously. We show these limitations can be mitigated via the use of deep learning-based supersampling of undersampled images acquired on a point-scanning system, which we term point-scanning super-resolution (PSSR) imaging. We designed a 'crappifier' that computationally degrades high SNR, high-pixel resolution ground truth images to simulate low SNR, low-resolution counterparts for training PSSR models that can restore real-world undersampled images. For high spatiotemporal resolution fluorescence time-lapse data, we developed a 'multi-frame' PSSR approach that uses information in adjacent frames to improve model predictions. PSSR facilitates point-scanning image acquisition with otherwise unattainable resolution, speed and sensitivity. All the training data, models and code for PSSR are publicly available at 3DEM.org.

Identification and Nursing Care of a Stroke Patient with Internal Iliac Artery Branch Rupture and Bleeding.

To summarize the experience of identifying and caring for a stroke patient with ruptured internal iliac artery branch bleeding. The experience was summarized in 3 aspects, including how to recognize the presence of active bleeding in the patient, confirmation of the diagnosis and treatment of the bleeding point, prevention of postoperative complications, and rehabilitation care. After aggressive treatment and care, the patient was discharged after 30 days of hospitalization and improved.

Establishment of a Prognostic Nomogram for Cancer-Specific Survival in Patients With Base-of-Tongue Squamous Cell Carcinoma: A Retrospective Study Based on the SEER Database.

BACKGROUND: The aim of this retrospective study was to construct and clinically apply a nomogram for cancer-specific survival (CSS) in patients diagnosed with base-of-tongue squamous cell carcinoma (BOTSCC) to predict their survival prognosis. METHODS: We collected 8448 patients diagnosed with BOTSCC during 2004-2015 from the Surveillance, Epidemiology, and End Results (SEER) database and divided 30% and 70% of them into validation and training cohorts, respectively. We utilized backward stepwise regression in the Cox model to select variables. Predictive variables were subsequently identified from the variables selected above by using multivariate Cox regression. The new survival model was compared with the American Joint Committee on Cancer (AJCC) prognosis model using the following variables: calibration curve, time-dependent area under the receiver operating characteristic curve (AUC), concordance index (C-index), integrated discrimination improvement (IDI), decision-curve analysis (DCA), and net reclassification improvement (NRI). RESULTS: A nomogram was established for predicting the CSS probability in patients with BOTSCC. Factors including sex, race, age at diagnosis, marital status, radiotherapy status, chemotherapy status, TNM AJCC stage, surgery status, tumor size, and months from diagnosis to treatment were selected through multivariate Cox regression as independent predictors of CSS. Calibration plots indicated that the model we established had satisfactory calibration ability. The AUC, C-index, IDI, DCA, and NRI results illustrated that the nomogram performed explicit prognoses more accurately than did the AJCC system alone. CONCLUSION: We identified the relevant factors affecting the survival of BOTSCC patients and analyzed the data on patients suffering from BOTSCC in the SEER database. These factors were used to construct a new nomogram to give clinical staff a more-visual prediction model for the 3-, 5-, and 8-year probabilities of CSS for patients newly diagnosed with BOTSCC, thereby aiding clinical decision making.

The Effect of Bicycle Saddle Widths on Saddle Pressure in Female Cyclists.

Choosing an unsuitable bicycle saddle increases the saddle pressure and discomfort during cycling. Women contract sports injuries more easily than men during cycling owing to their anatomy. To investigate the effect of saddle widths on the saddle pressure in female cyclists. Ten healthy women with an average age of 20.7 ± 1.3 years, height of 162 ± and 5.9 cm, weight of 56.1 ± 7.5 kg, and a sciatic bone width of 15.5 ± 1.4 cm were recruited for this study. The distributions of saddle pressure for four different saddle widths (i.e., narrow, moderate, wide, and self-chosen) were recorded using a saddle pressure mat. Participants were instructed to pedal steadily with a frequency of 90 RPM and a load of 150 watts. Thirty seconds of riding data was randomly retrieved for analysis. The trials were conducted with a counter-balanced design to minimize random errors. One-way repeated measures ANOVA was used to compare the saddle pressure of different saddle widths, and the significance level was set at α = 0.05. When wide saddles were used, the maximum and average pressure on the right surface of the posterior ischium were lower than those with narrow (p = 0.001, p = 0.012) and moderate (p = 0.016, p = 0.019) saddles. The area of pressure on the pubic bone was smaller when using a wide saddle than when using narrow (p = 0.005) and moderate (p = 0.018) saddles, and the area of pressure on the right posterior sciatic bone was larger under the wide saddle than under the narrow (p = 0.017) and moderate (p = 0.036) saddles. The average force was greater with the moderate saddle than with the wide (p = 0.008) and self-chosen (p = 0.025) saddles. Using a saddle with a width that is longer than the width of the cyclist's ischium by 1 cm can effectively improve the distribution of saddle pressure during riding, while providing better comfort.

Opportunistic bacteria use quorum sensing to disturb coral symbiotic communities and mediate the occurrence of coral bleaching.

Coral associated microorganisms, especially some opportunistic pathogens can utilize quorum-sensing (QS) signals to affect population structure and host health. However, direct evidence about the link between coral bleaching and dysbiotic microbiomes under QS regulation was lacking. Here, using 11 opportunistic bacteria and their QS products (AHLs, acyl-homoserine-lactones), we exposed Pocillopora damicornis to three different treatments: test groups (A and B: mixture of AHLs-producing bacteria and cocktail of AHLs signals respectively); control groups (C and D: group A and B with furanone added respectively); and a blank control (group E: only seawater) for 21 days. The results showed that remarkable bleaching phenomenon was observed in groups A and B. The operational taxonomic units-sequencing analysis shown that the bacterial network interactions and communities composition were significantly changed, becoming especially enhanced in the relative abundances of Vibrio, Edwardsiella, Enterobacter, Pseudomonas, and Aeromonas. Interestingly, the control groups (C and D) were found to have a limited influence upon host microbial composition and reduced bleaching susceptibility of P. damicornis. These results indicate bleaching's initiation and progression may be caused by opportunistic bacteria of resident microbes in a process under regulation by AHLs. These findings add a new dimension to our understanding of the complexity of bleaching mechanisms from a chemoecological perspective.

YWHAZ amplification/overexpression defines aggressive bladder cancer and contributes to chemo-/radio-resistance by suppressing caspase-mediated apoptosis.

The objective of this study was to characterize the oncogenic actions of a recently identified cancer-associated gene YWHAZ (also named as 14-3-3 ζ/δ) in urothelial carcinomas of the urinary bladder (UCUB). A genome-wide study revealed YWHAZ to be involved in the amplicon at 8q22.3, and its genetic amplification was detected predominantly in muscle-invasive bladder cancer (MIBC). Immunohistochemical staining confirmed the association of YWHAZ overexpression with higher tumor stages, lymph node/vascular invasion, and mitotic activity. Univariate and multivariate analyses further indicated the prognostic potential of YWHAZ for more aggressive cancer types. Both gene set enrichment analysis and STRING network studies suggested involvement of YWHAZ in regulating caspase-mediated apoptosis. Ectopic expression of YWHAZ in bladder cells with low endogenous YWHAZ levels boosted cell resistance to doxorubicin and cisplatin, as well as to ionizing radiation. Conversely, YWHAZ-knockdown using specific shRNA in cells with high endogenous YWHAZ levels diminished survival activity, suppressing cell growth and increasing cell death. Our findings confirm the essential role played by YWHAZ in sustaining cell proliferation during chemo/radiotherapy. Treatments based on anti-YWHAZ strategies may thus be beneficial for UCUB patients overexpressing YWHAZ. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Inhibition of Cgkii Suppresses Seizure Activity and Hippocampal Excitation by Regulating the Postsynaptic Delivery of Glua1.

BACKGROUND/AIMS: The imbalance between excitation and inhibition is a defining feature of epilepsy. GluA1 is an AMPA receptor subunit that can strengthen excitatory synaptic transmission when upregulated in the postsynaptic membrane, which has been implicated in the pathogenesis of epilepsy. cGKII, a cGMP-dependent protein kinase, regulates the GluA1 levels at the plasma membrane. METHODS: To explore the role of cGKII in epilepsy, we investigated the expression of cGKII in patients with temporal lobe epilepsy (TLE) and in a pilocarpine-induced rat model and then performed behavioral, histological, and electrophysiological analyses by applying either a cGKII agonist or inhibitor in the hippocampus of the animal model. RESULTS: cGKII expression was upregulated in the epileptogenic brain tissues of both humans and rats. Pharmacological activation or inhibition of cGKII induced changes in epileptic behaviors in vivo and epileptic discharges in vitro. Further studies indicated that cGKII activation disrupted the balance of excitation and inhibition due to strengthened AMPAR-mediated excitatory synaptic transmission. Moreover, cGKII regulated epileptic seizures by phosphorylating GluA1 at Ser845 to modulate the expression and function of GluA1 in the postsynaptic membrane. CONCLUSION: These results suggest that cGKII plays a key role in seizure activity and could be a potential therapeutic target for epilepsy.

Research Progress of Risk Factors Associated with Gestational Diabetes Mellitus.

Gestational Diabetes Mellitus (GDM) is a common endocrine condition associated with adverse pregnancy outcomes. In recent years, a growing number of risk factors associated with gestational diabetes mellitus have been defined. GDM poses a serious threat to maternal health. The etiology is complex and multifactorial and can be divided into inherent and modifiable factors. The inherent factors have been described in other literature, while the modifiable factors are mainly the risk of lifestyle habits. In this study, we performed a narrative review of the progress of risk factors associated with gestational diabetes mellitus.

Essential trace elements in patients with dyslipidemia: A meta-analysis.

BACKGROUND: Lipid metabolism is a complex process that includes lipid uptake, transport, synthesis, and degradation. Trace elements are vital in maintaining normal lipid metabolism in the human body. This study explores the relationship between serum trace elements and lipid metabolism Methods: In this study, we reviewed articles on the relationship between alterations in somatic levels of zinc, iron, calcium, copper, chrome, manganese, selenium, and lipid metabolism. In this systematic review and mate-analysis, databases such as PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI), Wanfang was searched for articles on the relationship published between January 1, 1900, and July 12, 2022. The meta-analysis was performed using Review Manager5.3 (Cochrane Collaboration). RESULTS: No significant association was found between serum zinc and dyslipidemia, while other serum trace elements (Iron, selenium, copper, chromium, and manganese) were associated with hyperlipidemia. CONCLUSION: The present study suggested that the human body's zinc, copper, and calcium content may be related to lipid metabolism. However, findings on lipid metabolism and Iron, Manganese have not been conclusive. In addition, the relationship between lipid metabolism disorders and selenium levels still needs to be further studied. Further research is needed on treating lipid metabolism diseases by changing trace elements.

Vemurafenib induces a noncanonical senescence-associated secretory phenotype in melanoma cells which promotes vemurafenib resistance.

More than one half melanoma patients have BRAF gene mutation. BRAF inhibitor vemurafenib is an effective medication for these patients. However, acquired resistance is generally inevitable, the mechanisms of which are not fully understood. Cell senescence and senescence-associated secretory phenotype (SASP) are involved in extensive biological functions. This study was designed to explore the possible role of senescent cells in vemurafenib resistance. The results showed that vemurafenib treatment induced BRAF-mutant but not wild-type melanoma cells into senescence, as manifested by positive ß-galactosidase staining, cell cycle arrest, enlarged cellular morphology, and cyclin D1/p-Rb pathway inhibition. However, the senescent cells induced by vemurafenib (SenV) did not display DNA damage response, p53/p21 pathway activation, reactive oxygen species accumulation, decline of mitochondrial membrane potential, or secretion of canonical SASP cytokines. Instead, SenV released other cytokines, including CCL2, TIMP2, and NGFR, to protect normal melanoma cells from growth inhibition upon vemurafenib treatment. Xenograft experiments further confirmed that vemurafenib induced melanoma cells into senescence in vivo. The results suggest that vemurafenib can induce robust senescence in BRAFV600E melanoma cells, leading to the release of resistance-conferring cytokines. Both the senescent cells and the resistant cytokines could be potential targets for tackling vemurafenib resistance.

Recent advances of artificial intelligence in melanoma clinical practice.

Skin melanoma is a lethal cancer. The incidence of melanoma is increasing rapidly in all regions of the world. Despite significant breakthroughs in melanoma treatment in recent years, precise diagnosis of melanoma is still a challenge in some cases. Even specialized physicians may need time and effort to make accurate judgments. As artificial intelligence (AI) technology advances into medical practice, it may bring new solutions to this problem based on its efficiency, accuracy, and speed. This paper summarizes the recent progress of AI in melanoma-related applications, including melanoma diagnosis and classification, the discovery of new medication, guiding treatment, and prognostic assessment. The paper also compares the effectiveness of various algorithms in melanoma application and suggests future research directions for AI in melanoma clinical practice.

α-Viniferin-Induced Apoptosis through Downregulation of SIRT1 in Non-Small Cell Lung Cancer Cells.

α-Viniferin, a natural stilbene compound found in plants and a polymer of resveratrol, had demonstrated potential anti-cancer and anti-inflammatory effects. However, the specific mechanisms underlying its anti-cancer activity were not yet fully understood and required further investigation. This study evaluated the effectiveness of α-viniferin and ε-viniferin using MTT assay. Results showed that α-viniferin was more effective than ε-viniferin in reducing the viability of NCI-H460 cells, a type of non-small cell lung cancer. Annexin V/7AAD assay results provided further evidence that the decrease in cell viability observed in response to α-viniferin treatment was due to the induction of apoptosis in NCI-H460 cells. The present findings indicated that treatment with α-viniferin could stimulate apoptosis in cells by cleaving caspase 3 and PARP. Moreover, the treatment reduced the expression of SIRT1, vimentin, and phosphorylated AKT, and also induced AIF nuclear translocation. Furthermore, this research provided additional evidence for the effectiveness of α-viniferin as an anti-tumor agent in nude mice with NCI-H460 cell xenografts. As demonstrated by the TUNEL assay results, α-viniferin promoted apoptosis in NCI-H460 cells in nude mice.

Lower Limb Biomechanics during the Golf Downswing in Individuals with and without a History of Knee Joint Injury.

Although prevention is better than treatment, after a knee injury occurs, the adjustment of the movement technique back to the posture before the injury and the restoration of accuracy is very important for professional and amateur players. This study aimed to compare the differences in lower limb mechanics during the golf downswing between those with and without a history of knee joint injury. A total of 20 professional golfers with single-digit handicaps were recruited for this study, 10 of whom had a knee injury history (KIH+), while another 10 players were without a knee injury history (KIH-). From the 3D analysis, selected kinematic and kinetic parameters during the downswing were analyzed using an independent samples t-test with a significance level of α = 0.05. During the downswing, individuals with KIH+ exhibited a smaller hip flexion angle, smaller ankle abduction angle, and larger ankle adduction/abduction range of motion (ROM). Moreover, there was no significant difference found in the knee joint moment. Athletes with a history of knee injury can adjust the motion angles of their hip and ankle joints (e.g., by avoiding excessive forward leaning of the trunk and maintaining stable foot posture without inward or outward rotation) to minimize the impact of changes in their movement patterns resulting from the injury.

Comment "Asymptomatic small intestinal ulcerative lesions: Obesity and Helicobacter pylori are likely to be risk factors".

There are many causes of anemia. It is unreasonable to simply associate anemia with asymptomatic ulcers in the small intestine.

Skinny people serum factors promote the differentiation of multipotent stem cells into brown adipose tissue.

The original study by Alessio et al reported that skinny people (SP) serum can promote the formation of brown adipocytes, but not the differentiation of white adipocytes. This finding may explain why SP do not often become obese, despite consuming more calories than the body needs. More importantly, they demonstrated that circulating factors in SP serum can promote the expression of UCP-1 protein, thereby reducing fat accumulation. In this study, only male serum samples were evaluated to avoid the interference of sex hormones in experiments, but adult males also synthesize estrogen, which is produced by the cells of the testes. At the same time, adult females secrete androgens, and females synthesize androgens that are mainly produced by the adrenal cortex. We believe that the approach of excluding sex hormone interference by sex selection alone may be flawed, so we comment on the article and debate the statistical analysis of the article.

α-Viniferin and ε-Viniferin Inhibited TGF-ß1-Induced Epithelial-Mesenchymal Transition, Migration and Invasion in Lung Cancer Cells through Downregulation of Vimentin Expression.

Resveratrol has well-known anticancer properties; however, its oligomers, including α-viniferin, ε-viniferin, and kobophenol A, have not yet been well investigated. This is the first study examining the anti-epithelial-mesenchymal transition (EMT) effects of α-viniferin and ε-viniferin on A549, NCI-H460, NCI-H520, MCF-7, HOS, and U2OS cells. The results showed that α-viniferin and ε-viniferin significantly inhibited EMT, invasion and migration in TGF-ß1- or IL-1ß-induced non-small cell lung cancer. α-Viniferin and ε-viniferin also reversed TGF-ß1-induced reactive oxygen species (ROS), MMP2, vimentin, Zeb1, Snail, p-SMAD2, p-SMAD3, and ABCG2 expression in A549 cells. Furthermore, ε-viniferin was found to significantly inhibit lung metastasis in A549 cell xenograft metastatic mouse models. In view of these findings, α-viniferin and ε-viniferin may play an important role in the prevention of EMT and cancer metastasis in lung cancer.

Jolkinolide B sensitizes bladder cancer to mTOR inhibitors via dual inhibition of Akt signaling and autophagy.

The monotherapy of mTOR inhibitors (mTORi) in cancer clinical practice has achieved limited success due to the concomitant activation of compensatory pathways, such as Akt signaling and cytoprotective autophagy. Thus, the combination of mTORi and the inhibitors of these pro-survival pathways has been considered a promising therapeutic strategy. Herein, we report the synergistic effects of a natural anti-cancer agent Jolkinolide B (JB) and mTORi (temsirolimus, rapamycin, and everolimus) for the effective treatment of bladder cancer. A mechanistic study revealed that JB induced a dual inhibition of Akt feedback activation and cytoprotective autophagy, potentiating the anti-proliferative efficacy of mTORi in both PTEN-deficient and cisplatin-resistant bladder cancer cells. Meanwhile, mTORi augmented the pro-apoptotic and pro-paraptotic effects of JB by reinforcing JB-activated endoplasmic reticulum stress and MAPK pathways. These synergistic mechanisms were related to cellular reactive oxygen species accumulation. Our study suggests that dual inhibition of Akt feedback activation and cytoprotective autophagy is an effective strategy in mTORi-based therapy, and JB + mTORi combination associated with multiple anti-cancer mechanisms and good tolerance in mouse models may serve as a promising treatment for bladder cancer.

Different nutrient compositions in diet and taking hypoglycemic drugs can modulate gut microbial flora.

The diet structure of diabetic patients is different from that of normal people. Diabetic patients also need to take hypoglycemic drugs to regulate blood sugar. Both dieting and drugs affect the gut microbiota of diabetic patients. In this letter, we discuss that different dietary patterns and the use of hypoglycemic agents may have an impact on changes in gut microbiota in diabetic patients.

Celastrol Inhibits Canine Mammary Tumor Cells by Inducing Apoptosis via the Caspase Pathway.

Canine mammary tumor is a serious disease threatening the health of dogs and can be used as a research model for human breast cancer. The study of canine mammary tumor has a role in improving the welfare of dogs. Most common canine mammary tumor chemotherapy drugs have limited effects and drug resistance. Celastrol is an extract of Tripterygium wilfordii, which has a wide range of biological activities, including significant anti-tumor effects. At present, celastrol has not been used in the clinical treatment for canine mammary tumor. This study investigated the anti-tumor properties of celastrol through in vitro assay of cell proliferation inhibition, cell colony, cell migration, and invasion; flow cytometry, qPCR, and Western Blot methods were used to explore the anti-tumor mechanism of celastrol. The results showed that celastrol can inhibit the proliferation of canine mammary tumor cells in vitro, and decrease the migration and invasion ability of canine mammary tumor cells. We also found that celastrol can upregulate Cleaved Caspase-3 and Cleaved Caspase-9 protein expression levels to promote cell apoptosis, and can regulate cell cycle-related proteins to induce cell cycle arrest. In summary, celastrol may inhibit canine mammary tumor cells through the Caspase pathway, providing a new direction for anti-canine mammary tumor drugs, and is expected to become a new anti-cancer drug for canine mammary tumors.

ε-Viniferin and α-viniferin alone or in combination induced apoptosis and necrosis in osteosarcoma and non-small cell lung cancer cells.

This study investigated the effects and molecular mechanisms of ε-viniferin and α-viniferin in non-small cell lung cancer cell line A549, melanoma cell line A2058, and osteosarcoma cell lines HOS and U2OS. Results showed ε-viniferin having antiproliferative effects on HOS, U2OS, and A549 cells. Compared with ε-viniferin at the same concentration, α-viniferin had higher antiproliferative effects on HOS cells, but not the same effect on U2OS and A549 cells. Lower dose combination of α-viniferin and ε-viniferin had more synergistic effects on A549 cells than either drug alone. α-Viniferin induced apoptosis in HOS cells by decreasing expression of phospho-c-Jun-N-terminal kinase 1/2 (p-JNK1/2) and increasing expression of cleaved Poly (ADP-ribose) polymerase (PARP), whereas α-viniferin in combination with ε-viniferin induced apoptosis in A549 cells by decreasing expression of phospho-protein kinase B (p-AKT) and increasing expression of cleaved PARP and cleaved caspase-3. ε-Viniferin and α-viniferin have not been studied using in vivo tumor models for cancer. This research is the first showing that ε-viniferin treatment resulted in significant inhibition of tumor growth in A549-cell xenograft-bearing nude mice compared with the control group. Consequently, ε-viniferin and α-viniferin may prove to be new approaches and effective therapeutic agents for osteosarcoma and lung cancer treatment.