Deciphering and integrating invariants for neural operator learning with various physical mechanisms.

Neural operators have been explored as surrogate models for simulating physical systems to overcome the limitations of traditional partial differential equation (PDE) solvers. However, most existing operator learning methods assume that the data originate from a single physical mechanism, limiting their applicability and performance in more realistic scenarios. To this end, we propose the physical invariant attention neural operator (PIANO) to decipher and integrate the physical invariants for operator learning from the PDE series with various physical mechanisms. PIANO employs self-supervised learning to extract physical knowledge and attention mechanisms to integrate them into dynamic convolutional layers. Compared to existing techniques, PIANO can reduce the relative error by 13.6%-82.2% on PDE forecasting tasks across varying coefficients, forces or boundary conditions. Additionally, varied downstream tasks reveal that the PI embeddings deciphered by PIANO align well with the underlying invariants in the PDE systems, verifying the physical significance of PIANO.

Anesthetic propofol epigenetically regulates breast cancer trastuzumab resistance through IL-6/miR-149-5p axis.

Propofol, a common intravenous anesthetic, has been found to exert anti-cancer effects with inhibition of cancer cell proliferation, migration and invasion. We tested its possible action against HER2-overexpressing breast cancer cells that developed resistance against trastuzumab. Cell viability assay, ELISA for cytokines, mammosphere formation, quantitative RT-PCR for EMT/IL-6-targeting miRNAs and the in vivo experimental pulmonary metastasis model were performed to understand the epigenetic action of propofol. Propofol sensitized HER2 overexpressing cells to trastuzumab but such action was even more pronounced in resistant cells. Increased cytokines IL-6 as well as IL-8 were released by resistant cells, along with increased mammospheres and induction of EMT, all of which was inhibited by propofol. IL-6 targeting tumor suppressor miR-149-5p was found to be the novel miRNA that was up-regulated by propofol, resulting in the observed effects on cell viability, IL-6 production, mammospheres generation as well as EMT induction. Further, antagonizing miR-149-5p attenuated the propofol effects confirming the epigenetic activity of propofol through miR-149-5p regulation. Finally, in vivo validation in an experimental metastasis model conformed an inhibitory action of propofol against experimental lung metastasis and the essential mechanistic role of miR-149-5p/IL-6 loop. These results present a novel role of general anesthetic propofol against resistant breast cancer cells and the underlying epigenetic regulation of a tumor suppressor miRNA.

A novel case of cutaneous squamous cell carcinoma at the site of previous sporotrichosis.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a malignant tumor of epithelial keratinocytes, with a relatively reduced frequency of lymph node metastasis. Despite the fact that this tumor type is largely preventable, the incidence of cSCC is rising every year. Ultraviolet exposure is a major cause of cSCC and directly contributes to cSCC. Other known environmental risk factors include ionizing radiation, cigarette smoking, and certain chemical exposures. AIMS: In this study, we report a clinical case of cSCC with a novel causative factor. PATIENT/METHODS: The report describes a 72-year-old male who was seen for a dermatosis condition initially. Later, epidermal hyperplasia and granulomatous inflammation of the dermis was diagnosed based on skin biopsy. Fungal culture revealed the presence of Sporothrix schenckii which led to the diagnosis of fixed-type sporotrichosis. RESULTS: Four months of oral terbinafine (250 mg once a day) administration partially resolved the lesions. Patient was subsequently diagnosed with cSCC, and surgical resection with wider margins was performed. CONCLUSION: After a careful and rigorous exclusion of known risk factors, we confirmed that this incidence of cSCC was caused by chronic inflammation which followed fixed-type sporotricosis.

High-throughput lipidomics analysis to discover lipid biomarkers and profiles as potential targets for evaluating efficacy of Kai-Xin-San against APP/PS1 transgenic mice based on UPLC-Q/TOF-MS.

Lipid metabolism has a significant function in the central nervous system and Alzheimer's disease (AD) is an age-related senile disease characterized by central nerve degeneration. The pathological development of AD is closely related to lipid metabolism disorders. To reveal the influence of Kai-Xin-San (KXS) on lipid metabolism in APP/PSI transgenic mice and potential therapeutic targets for treating AD, brain tissue samples were collected and analyzed by high-throughput lipidomics based on UPLC-Q/TOF-MS. The collected raw data were processed by multivariate data analysis to discover the potential biomarkers and lipid metabolic profiles. Compared with the control wild-type mouse group, nine potential lipid biomarkers were found in the AD model group, of which seven were up-regulated and two were down-regulated. Orally administrated KXS can reverse the changes in these potential biomarkers. Compared with the model group, a total of six differential metabolites showed a recovery trend and may be potential targets for KXS to treat AD. This study showed that high-throughput lipidomics can be used to discover the perturbed pathways and lipid biomarkers as potential targets to reveal the therapeutic effects of KXS.

High-Throughput Metabolomics Evaluate the Efficacy of Total Lignans From Acanthophanax Senticosus Stem Against Ovariectomized Osteoporosis Rat.

Postmenopausal osteoporosis (PMOP) is a common clinical illness in postmenopausal women, but there is no effective drug at present. Metabolomics approach was used to explore the potential biomarkers of PMOP and evaluate the efficacy and therapeutic targets of total lignans in the stem of Acanthophanax senticosus (ASSL) on the ovariectomized osteoporosis model rats. UPLC/MS and pattern recognition methods were used for serum metabolites discovery to illustrate the pathological mechanism of PMOP model rats, and then revealing the intervention effect of ASSL. The pattern recognition result showed that serum metabolic profiles of the sham operation group and the model group were clustered clearly, and 16 potential biomarkers were finally identified (7 in positive ion mode and 9 in negative ion mode), and they are involved in 15 related metabolic pathways. After oral administration of ASSL, 10 biomarkers were found to be significantly up-regulated and mainly regulated metabolic pathways include unsaturated fatty acid biosynthesis, linoleic acid metabolism, and arachidonic acid metabolism, primary bile acid synthesis, tyrosine metabolism, etc. Our study demonstrated that the ASSL could affect the endogenous metabolites related metabolic mechanism, provides a pharmacological basis of the ASSL for PMOP treatment.

[Updated roles of SIRT1 in prostate diseases].

Silent information regulator 1(SIRT1),an NAD+dependent class-III histone deacetylase,is implicated in diverse cellular processes. SIRT1 has been reported as a key regulator of metabolism,oxidative stress,and cell survival,proliferation,apoptosis and autophagy. It also plays an important role in a variety of physiological processes and health conditions,including aging,inflammation,metabolic disease,tumor,cardiovascular disease,and neurodegeneration. In recent years,the incidence of prostate diseases is increasing,but the therapeutic options are relatively limited. The importance of SIRT1 in prostate diseases has become increasingly apparent,and more rational application of sirtuin inhibitors or activators is shedding new light on the management of prostate diseases.This review focuses on the role of SIRT1 in prostate diseases and introduces some novel strategies for their diagnosis and treatment.

A new method for modeling coalescent processes with recombination.

BACKGROUND: Recombination plays an important role in the maintenance of genetic diversity in many types of organisms, especially diploid eukaryotes. Recombination can be studied and used to map diseases. However, recombination adds a great deal of complexity to the genetic information. This renders estimation of evolutionary parameters more difficult. After the coalescent process was formulated, models capable of describing recombination using graphs, such as ancestral recombination graphs (ARG) were also developed. There are two typical models based on which to simulate ARG: back-in-time model such as ms and spatial model including Wiuf&Hein's, SMC, SMC', and MaCS. RESULTS: In this study, a new method of modeling coalescence with recombination, Spatial Coalescent simulator (SC), was developed, which considerably improved the algorithm described by Wiuf and Hein. The present algorithm constructs ARG spatially along the sequence, but it does not produce any redundant branches which are inevitable in Wiuf and Hein's algorithm. Interestingly, the distribution of ARG generated by the present new algorithm is identical to that generated by a typical back-in-time model adopted by ms, an algorithm commonly used to model coalescence. It is here demonstrated that the existing approximate methods such as the sequentially Markov coalescent (SMC), a related method called SMC', and Markovian coalescent simulator (MaCS) can be viewed as special cases of the present method. Using simulation analysis, the time to the most common ancestor (TMRCA) in the local trees of ARGs generated by the present algorithm was found to be closer to that produced by ms than time produced by MaCS. Sample-consistent ARGs can be generated using the present method. This may significantly reduce the computational burden. CONCLUSION: In summary, the present method and algorithm may facilitate the estimation and description of recombination in population genomics and evolutionary biology.

Monitoring of peptide-specific and gamma interferon-productive T cells in patients with active and convalescent tuberculosis using an enzyme-linked immunosorbent spot assay.

To establish a high-efficiency gamma interferon-specific enzyme-linked immunosorbent spot assay (IFN-γ ELISPOT assay) for detection of tuberculosis (TB), peptides (E6, E7, and C14) and peptide mixtures (E6 plus E7 and E6 plus E7 plus C14) were used to monitor peripheral blood (PBL) samples from patients with pulmonary TB (PTB), as well as control samples. The positive detection rates of the five IFN-γ ELISPOT assays were 78.38%, 74.86%, 55.83%, 90.43%, and 91.51%, respectively, and there were similar detection rates between the two combined peptide mixture IFN-γ ELISPOT assays and the tuberculin skin test (TST) (90.62% versus 95.59%). No significant difference was found between the detection rates of the two combined peptide mixture IFN-γ ELISPOT assays and the T-SPOT.TB assay for 86 patients with PTB (P > 0.05), but the median number of spot-forming cells/10(6) cells (SFP value) for positive results was higher by the former than by the latter assay (P < 0.05). In contrast, the 29.93% positive detection rate and median SFP value of 482 by the two combined peptide mixture IFN-γ ELISPOT assays were significantly higher than the corresponding values of 14.29% and 152 by T-SPOT.TB assay for the same 147 community donors (P < 0.05). For nine PTB patients tracked, the SFP value of 7 for the two peptide mixture IFN-γ ELISPOT assays began to decrease from the second month after regular treatment. A relatively low, almost normal, SFP level was reached and maintained after the third or fourth month. Two in-house IFN-γ ELISPOT assays and the T-SPOT.TB assay could reduce the false-positive and false-negative detection rates of TST and sputum acid-fast staining. Therefore, these two combined peptide mixture IFN-γ ELISPOT assays have a potential advantage, beyond their greater specificity and sensitivity, for use in screening and detection of active TB infection (TBI) and latent TB infection (LTBI) in China.

Efficient simulation under a population genetics model of carcinogenesis.

MOTIVATION: Cancer is well known to be the end result of somatic mutations that disrupt normal cell division. The number of such mutations that have to be accumulated in a cell before cancer develops depends on the type of cancer. The waiting time T(m) until the appearance of m mutations in a cell is thus an important quantity in population genetics models of carcinogenesis. Such models are often difficult to analyze theoretically because of the complex interactions of mutation, drift and selection. They are also computationally expensive to simulate because of the large number of cells and the low mutation rate. RESULTS: We develop an efficient algorithm for simulating the waiting time T(m) until m mutations under a population genetics model of cancer development. We use an exact algorithm to simulate evolution of small cell populations and coarse-grained τ-leaping approximation to handle large populations. We compared our hybrid simulation algorithm with the exact algorithm in small populations and with available asymptotic results for large populations. The comparison suggested that our algorithm is accurate and computationally efficient. We used the algorithm to study the waiting time for up to 20 mutations under a Moran model with variable population sizes. Our new algorithm may be useful for studying realistic models of carcinogenesis, which incorporates variable mutation rates and fitness effects.

[Expression of aquaporin-4 protein in rats with acute radiation-induced cerebral edema].

OBJECTIVE: To explore the relation between changes in expression of aquaporin-4(AQP4) protein and acute radiation-induced cerebral edema after Gamma knife radiation. METHODS: The experimental model was established in rats by radiating 2 mm right to median line in cerebral hemisphere with 50 Gy Gamma knife (the center located at the line of auditory canal). The changes of brain water content were measured by the wet and dry weight method. Immunohistochemistry was used to determine the change of expression of AQP4 protein at different periods after Gamma knife radiation. RESULTS: The brain water content and the expression of AQP4 in the target area and the peripheral zone obviously increased at 12 h after Gamma knife radiation, and achieved the peak after 2 d. It was still higher than normal after 14 d. The gray value of expression of aquaporin-4 was negatively related to brain water content (r=-0.9857, P<0.05). CONCLUSION: AQP4 has a close relationship with acute radiation-induced cerebral edema.

[Gamma knife treatment for pituitary prolactinomas].

OBJECTIVE: To evaluate the outcome of gamma knife for prolactinomas. METHODS: Eighty-nine patients were treated by gamma knife and 51 were followed up. The dose to the tumor margin ranged from 18 Gy to 35 Gy (mean 26.1 Gy). The maximum radiation dose varied from 36 Gy to 60 Gy (mean 50.41 Gy). The mean tumor diameter was 15.5 mm (5 - 26 mm). RESULTS: The follow-up data were available for 51 patients ranging from 6 to 108 months (mean 37 months). The tumor growth control rate was 100%. The endocrinological remission rate was 40%. The rate of hypopituitarism was 17.6%. CONCLUSION: Gamma knife radiosurgery can be used as a primary treatment for selected prolactinomas,especially for pituitary microadenomas.

[Evaluation of strand displacement amplification in the diagnosis of tuberculosis].

OBJECTIVE: To study the clinical significance and reliability of strand displacement amplification (SDA) in detecting Mycobacterium tuberculosis complex. METHODS: SDA and fluorescence quantitative polymerase chain reaction (FQ-PCR) were employed to detect samples from 453 cases of tuberculosis, including 332 sputum samples, 78 samples of pleural effusion, and 43 samples of cerebrospinal fluid. RESULTS: In the 332 sputum samples, 131 were culture-positive, of which 110 samples (88 smear-positive) were Mycobacterium tuberculosis complex and 21 samples (20 smear-positive) were nontuberculous Mycobacteria. The sensitivity and specificity of SDA for the 110 samples of Mycobacterium tuberculosis complex and 21 samples of nontuberculous Mycobacteria were 99.1%, 95.2% and 94.6%, 95.2%, respectively. The positive rates in the 311 cases of Mycobacterium tuberculosis complex for SDA and FQ-PCR were 55.3% (172/311) and 47.0% (146/311), respectively. There were 20 smear positive samples in the 121 samples of pleural effusion and cerebrospinal fluid, of which 19 were Mycobacterium tuberculosis, 1 nontuberculous Mycobacterium. The positive rates for SDA and FQ-PCR were 43.4% (52/120) and 33.4% (40/120), respectively. Internal amplification control (IAC) was designed for SDA to achieve accuracy of the results. CONCLUSION: The automatic assay system of SDA is a rapid and specific test for detecting Mycobacterium tuberculosis complex.

[Gamma knife treatment for pituitary adenomas].

OBJECTIVE: To evaluate the function and effect of Gamma knife radiosurgery (GKR) in controlling the tumor growth and improving endocrinological abnormality of pituitary adenomas. METHODS: Two hundred and twenty-eight cases of pituitary adenoma were treated with Leksell Gamma knife. 1.0 Tesla MRI and Gamma-Plan system were used to orientate the tumor. The margin dose was 12 - 35 Gy, mean 21.3 Gy; the center does was 24 - 70 Gy, mean 46.6 Gy (NFA, 31.8 Gy; FA, 50.3 Gy). RESULTS: One hundred and sixteen cases (NFA, 28; FA, 88) were followed up for 4 - 67 months, and the mean was 27.4 months. The growth of tumors in 113 cases (97.4%) was controlled. The tumor volume became smaller in 98 cases (84.5%). Three cases (2.6%) grew larger in tumor size. A significant decrease of excessive hormone production was seen in 89.8% of the patients, and the endocrinological normalization rate was 49.7% (PRL, 47.2%; GH, 57.1%; ACTH, 55.6%). Postradiosurgical complications were seen in 6%. CONCLUSION: Gamma knife radiosurgery is safe and effective in controlling the tumor growth and improving endocrinological abnormality of pituitary adenoma.

Thirty-one patients with primary hepatocellular carcinoma survived for more than 5 years after hepatectomy.

OBJECTIVE: To investigate the factors affecting prognosis of patients with primary hepatocellular carcinoma (PHC) after resection. METHODS: From 1976 to 1992, 213 patients with PHC treated with hepatectomy were followed up for more than 5 years. Thirty-one of the patients who had survived for more than 5 years were compared with 56 patients who had survived for less than 5 years. RESULTS: Early detection of tumor, radical resection, number of tumors, capsule formation, operation safe distance, presence of portal tumor embolus, presence of cirrhosis and tumor size were important factors affecting the prognosis of patients with PHC. The proportion of small liver cancer in the patients who had survived for more than 5 years was greatly larger than that in the control group. CONCLUSIONS: Early detection of tumor and radical resection are of value in raising the 5-year survival rate. Much remains to be investigated about the relationship between safe margin distance and prognosis of patients with PHC.