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Nonconvex minimax problems have attracted significant interest in machine learning and many other fields in recent years. In this paper, we propose a new zeroth-order alternating randomized gradient projection algorithm to solve smooth nonconvex-linear problems and its iteration complexity to find an ε -first-order Nash equilibrium is O ε - 3 and the number of function value estimation per iteration is bounded by O d x ε - 2 . Furthermore, we propose a zeroth-order alternating randomized proximal gradient algorithm for block-wise nonsmooth nonconvex-linear minimax problems and its corresponding iteration complexity is O K 3 2 ε - 3 and the number of function value estimation is bounded by O d x ε - 2 per iteration. The numerical results indicate the efficiency of the proposed algorithms. [ABSTRACT FROM AUTHOR]

As a lethal infectious disease, tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb). Its complex pathophysiological process limits the effectiveness of many clinical treatments. By regulating host cell death, Mtb manipulates macrophages, the first line of defense against invading pathogens, to evade host immunity and promote the spread of bacteria and intracellular inflammatory substances to neighboring cells, resulting in widespread chronic inflammation and persistent lung damage. Autophagy, a metabolic pathway by which cells protect themselves, has been shown to fight intracellular microorganisms, such as Mtb, and they also play a crucial role in regulating cell survival and death. Therefore, host-directed therapy (HDT) based on antimicrobial and anti-inflammatory interventions is a pivotal adjunct to current TB treatment, enhancing anti-TB efficacy. In the present study, we showed that a secondary plant metabolite, ursolic acid (UA), inhibited Mtb-induced pyroptosis and necroptosis of macrophages. In addition, UA induced macrophage autophagy and enhanced intracellular killing of Mtb. To investigate the underlying molecular mechanisms, we explored the signaling pathways associated with autophagy as well as cell death. The results showed that UA could synergistically inhibit the Akt/mTOR and TNF-α/TNFR1 signaling pathways and promote autophagy, thus achieving its regulatory effects on pyroptosis and necroptosis of macrophages. Collectively, UA could be a potential adjuvant drug for host-targeted anti-TB therapy, as it could effectively inhibit pyroptosis and necroptosis of macrophages and counteract the excessive inflammatory response caused by Mtb-infected macrophages via modulating the host immune response, potentially improving clinical outcomes. [ABSTRACT FROM AUTHOR]

Laminarinases reveal potential application in the field of food and biotechnology. In this research, a novel GH16 family laminarinase, designated as Lam16A_Wa, was cloned from the genome of marine bacterium Wenyingzhuangia aestuarii OF219 and expressed in Escherichia coli. Lam16A_Wa demonstrates a relatively low optimal reaction temperature (35°C) and a cold-adapted feature. Its optimal pH value is 6.0 and is stable in a broad pH range from 3.0 to 11.0. A glycomics strategy was employed to investigate the hydrolytic pattern of Lam16A_Wa. The enzyme was confirmed as a random endo-acting glycoside hydrolase. Its minimum substrate was laminarin pentasaccharide, and the major final products are oligosaccharides, including disaccharide to pentasaccharide. The Lam16A_Wa provides a novel and well-defined tool for the molecular tailoring of laminarin. [ABSTRACT FROM AUTHOR]

Understanding and mastering the structural evolution of water oxidation electrocatalysts lays the foundation to finetune their catalytic activity. Herein, we demonstrate that surface reconstruction of spinel oxides originates from the metal-oxygen covalency polarity in the MT–O–MO backbone. A stronger MO–O covalency relative to MT–O covalency is found beneficial for a more thorough reconstruction towards oxyhydroxides. The structure-reconstruction relationship allows precise prediction of the reconstruction ability of spinel pre-catalysts, based on which the reconstruction degree towards the in situ generated oxyhydroxides can be controlled. The investigations of oxyhydroxides generated from spinel pre-catalysts with the same reconstruction ability provide guidelines to navigate the cation selection in spinel pre-catalysts design. This work reveals the fundamentals for manipulating the surface reconstruction of spinel pre-catalysts for water oxidation. Precise control of water oxidation activity calls for the mastery of surface reconstruction of electrocatalysts. Here, the authors identify the structural origin of surface reconstruction on spinel oxides and report a criterion to evaluate the reconstruction degree, which enable the design of spinel pre-catalyst with controlled reconstruction ability. [ABSTRACT FROM AUTHOR]

Medermycin, produced by Streptomyces species, represents a family of antibiotics with significant activity against Gram-positive pathogens. The biosynthesis of this family of natural products has been studied, and new skeletons related to medermycin have rarely been reported until recently. Herein, we report eight chimeric medermycin-type natural products with unusual polycyclic skeletons. The formation of these compounds features some key nonenzymatic steps, which inspired us to construct complex polycyclic skeletons via three efficient one-step reactions under mild conditions. This strategy was further developed to efficiently synthesize analogues for biological activity studies. The synthetic compounds, chimedermycins L and M, and sekgranaticin B, show potent antibacterial activity against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and methicillin-resistant Staphylococcus epidermidis. This work paves the way for understanding the nonenzymatic formation of complex natural products and using it to synthesize natural product derivatives. Nonenzymatic reactions play an important part in the formation of some natural products possessing complex skeletons. Here, the authors report the discovery of eight chimeric medermycin-type natural products and their nonenzymatic construction. [ABSTRACT FROM AUTHOR]

In this paper, we study the minimax optimization problem that is nonconvex in one variable and linear in the other variable, which is a special case of nonconvex-concave minimax problem, which has attracted significant attention lately due to their applications in modern machine learning tasks, signal processing and many other fields. We propose a new alternating gradient projection algorithm and prove that it can find an ε -first-order stationary solution within O ε - 3 projected gradient step evaluations. Moreover, we apply it to solve the weighted maximin dispersion problem and the numerical results show that the proposed algorithm outperforms the state-of-the-art algorithms. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide (H2O2), as a signaling molecule, plays a vital role in a wide variety of signaling transduction processes, aging, and diseases. However, the excessive production of H2O2 causes various diseases. Herein, we develop a novel method for H2O2 detection in live cells via dark-field scattering spectroscopy with gold triangular nanoprisms (AuTNPs) as probes. The corners of AuTNPs would be gradually oxidatively etched by the strong coordination of Br• which is generated by enzymatic reactions in the presence of horseradish peroxidase (HRP), bromide ion and trace hydrogen peroxide. Benefitting from the morphological change, the single AuTNP based plasmonic nanoprobe shows notable blueshifts and scattering color changes which could be real-time monitored under the dark-field microscopy. The peak position in the scattering spectra of individual AuTNP blueshifts linearly with the increase of H2O2 concentration, and exhibits high sensitivity to H2O2 in a large range from 2.5 to 100 µM with a low detection limit (LOD) of 0.74 µM. Moreover, the experimental results were supported by the simulated results via the finite-difference time-domain (FDTD) method. The nanoprobes have been further used for intracellular H2O2 detection in live cells. Besides, the etching of AuTNP also provides an alternative method to design novel plasmonic logic chips and write-once plasmonic memories. [ABSTRACT FROM AUTHOR]

Finite rate of innovation sampling is a new signal sparse sampling method based on signal information freedom, which can considerably reduce the amount of sampling data. However, the researches on hardware circuit direct implementation of the method are at an initial stage. Therefore, a novel hardware circuit implementation method based on an exponential reproducing kernel (ERK) was developed with an improved ERK sparse sampling theoretical framework, which comprised an analog rational kernel (ARK) and digital rational kernel (DRK). The parameter constraint conditions and selection method for the improved ERK were analyzed. The performance of the ARK hardware circuit and the DRK algorithm were also examined. The designed sparse sampling system was applied to a pipeline flaw ultrasonic inspection by using the sparse sampling data of the ultrasonic signal obtained directly. The experimental results revealed that the proposed method could directly obtain the signal sparse sampling data and accurately reconstruct the initial signal parameters by using a spectrum estimation algorithm. Moreover, the signal sampling rate and the amount of sampling data were reduced considerably. [ABSTRACT FROM AUTHOR]

An exponential reproducing kernel (ERK) has been applied to data sparse sampling for finite rate of innovation (FRI) signals with the characteristic of flexible parameter setting in contrast to other sampling kernels. However, the signal reconstruction process may fail if a pulse echo is present in certain positions. To solve this problem, a novel ERK sparse sampling method was developed for arbitrary pulse echo positions. A constraint relationship between the pulse echo position and reproduced-exponent area was deduced, revealing the cause of invalid signal reconstruction from sparse sampling data. A new sampling time interval calculation algorithm is presented in this paper. Through the proposed method, FRI signals can be reconstructed accurately with a pulse echo present at arbitrary positions without increasing the quantity of sparse sampling data. The signal reconstruction effectiveness and accuracy were verified through simulation experiments. The proposed technique can be used to improve the flexibility of the ERK sparse sampling method in actual applications. [ABSTRACT FROM AUTHOR]

Notoginsenoside R1 (NGR1) is a predominant phytoestrogen extracted from Panax notoginseng that has recently been reported to play important roles in the treatment of cardiac dysfunction, diabetic kidney disease, and acute liver failure. Studies have suggested that NGR1 may be a viable treatment of hypoxic-ischemic brain damage (HIBD) in neonates by reducing endoplasmic reticulum stress via estrogen receptors (ERs). However, whether NGR1 has other neuroprotective mechanisms or long-term neuroprotective effects is unclear. In this study, oxygen-glucose deprivation/reoxygenation (OGD/R) in primary cortical neurons and unilateral ligation of the common carotid artery (CCL) in 7-day-old postnatal Sprague Dawley (SD) rats followed by exposure to a hypoxic environment were used to mimic an HIBD episode. We assessed the efficacy of NGR1 by measuring neuronal damage with MTT assay and assessed brain injury by TTC staining and brain water content detection 24-48 h after OGD/HIE. Simultaneously, we measured the long-term neurophysiological effects using the beam walking test (5 weeks after HI) and Morris water maze test 5-6 weeks after HI. Expression of PI3K-Akt-mTOR/JNK (24 h after HI or OGD/R) proteins was detected by Western blotting after stimulation with HI, NGR1, LY294002 (PI3K inhibitor), 740Y-P (PI3K agonist), or ICI 182780(estrogen receptors inhibitor). The results indicated that NGR1 exerted neuroprotective effects by inhibiting neuronal apoptosis and promoting cell survival via the PI3K-Akt-mTOR/JNK signaling pathways by targeting ER in neonatal hypoxic-ischemic injury. [ABSTRACT FROM AUTHOR]

Background: The measurement of the therapeutic outcome of cervical spine surgeries commonly relies on four main patient reported outcomes (PROs): Neck Disability Index (NDI), Visual Analog Scale (VAS) for pain, and Short Form-36 (SF-36) Physical (PCS) and Mental (MCS) Component Summary. However, the clinical impact of such scores and how they could effectively measure therapeutic efficacy remains unclear. In this context, the concept of minimum clinically important difference (MCID) is developing into the standard by which to evaluate treatments, patient satisfaction and cost-effectiveness. Methods: Eighty-eight consecutive patients undergoing surgery for subaxial degenerative cervical spine disease were selected from a prospective blinded database. PROs (NDI, PCS, MCS and VAS) were collected preoperatively, and together with blinded Surgeon Ratings (SR) at 3 months and 6 months post-surgery. Four anchor-based approaches were used to calculate different MCIDs. Three anchors (VAS, HTI (Health Transition Item of the SF-36) and SR) were used to evaluate surgery outcome. The best clinically and statistically relevant MCID was chosen. Results: On average, all patients presented with a statistically significant improvement ( p < 0.001) postoperatively for NDI (27.42 to 19.42), PCS (33.02 to 42.03), MCS (44 to 50.74) and VAS (2.85 to 1.93). The four MCID anchor-based approaches yielded a range of values for each PRO: 2.23–16.59 for PCS, 0.11–16.27 for MCS and 2.72–12.08 for NDI. When compared to the VAS and HTI anchors, the area under the ROC curve was greater for SR. This finding suggests that SR may be a more reliable anchor for MCID calculation. Conclusion: The MDC (minimum detectable change) approach together with the SR anchor appears to be the most appropriate MCID method. It offers the greatest area under the ROC curve (threshold above the 95 % CI), and the choice of the anchor did not significantly affect this result. MCID values for this dataset were 5.6 for PCS, 5.12 for MCS and 2.41 for NDI. [ABSTRACT FROM AUTHOR]

CCCTC-binding factor (CTCF), a multivalent zinc-finger protein, is involved in different aspects of regulation including promoter activation or repression, gene silencing, chromatin insulation, gene imprinting, X-chromosome inactivation, cell growth or differentiation and tumor genesis. However, the molecular mechanisms of CTCF nuclear import remains unclear. In this study, we showed that the expression of CTCF influenced the intracellular distribution of itself, which might go through transport receptor - import 13 (IPO13). We further confirmed that there is a CTCF target site in ipo13 −774∼−573 bp promoter region and CTCF regulates the expression of IPO13. Besides, GST pull-down and Co-IP experiments demonstrated that CTCF interacts with IPO13. Immunofluorescence staining showed that IPO13 influenced intracellular distribution of CTCF. In all, we conclude that CTCF regulates the expression of IPO13, which, in turn, mediates the nuclear import of CTCF. [ABSTRACT FROM AUTHOR]

Background: Few have studied the correlation between patients' and spine surgeons' perception on outcomes, or compared these with patient-reported outcome scores. Outcomes studies are increasingly important in evaluating costs and benefits to patients and surgeons, and in developing metrics for payer evaluation and health care policy-making. Objective: To compare patients' and surgeons' assessment of spine treatment outcome in a prospective blinded patient-driven spine surgery outcomes registry, and to correlate perceived outcomes ratings to validated outcomes scores. Methods: Patients filled out surveys at baseline, 3 months and 6 months postoperatively, including Visual Analog Scale (VAS), and Neck Disability Index (NDI) or Oswestry Disability Index (ODI). Outcome was rated independently by patients and surgeons on a 7-point Likert-type scale. Results: Two-hundred and sixty-five consecutive adult patients were surgical candidates. Of these, 154 (58.1 %) opted for surgery, with 69 (44.8 %) cervical and 85 (55.2 %) lumbar patients. One hundred and thirty-five (87.7 %) had both patient and surgeon postoperative ratings. Surgeons' and patients' ratings correlated strongly (Spearman rho = 0.53, p < 0.0001, 45.9 % identical, 88.2 % +/− 1 grade). The surgeon rated outcomes were better than patients in 29.8 % and worse in 21.15 %. Patient rating correlated better with the most recent NDI/ODI and pain scores than with incremental change from baseline. In multivariate analysis, age, location (cervical vs lumbar), pain ratings, and functional scores (NDI, ODI) did not have significant impact on the discrepancy between patient and surgeon ratings. Conclusions: Patients' and surgeons' global outcome ratings for spinal disease correlate highly. Patients' ratings correlate better with most recent functional scores, rather than incremental change from baseline. [ABSTRACT FROM AUTHOR]

Measurement of cell-free fetal DNA (cffDNA) is an indispensable process for non-invasive prenatal screening (NIPS). According to recent studies, cffDNA in maternal plasma can be enriched for various lengths of fragments, and a sufficient amount of cffDNA can effectively eliminate background interference on the part of maternal DNA. Therefore, we developed a simple and effective separation method, improved NIPS (iNIPS), that enriches the fetal fraction and improves the accuracy of NIPS for fetal aneuploid detection. We adopted a novel strategy to achieve enrichment of 125-135 bp cell-free DNA (cfDNA) by e-gel electrophoresis. To evaluate clinical performance, we compared NIPS and iNIPS results from 2153 retrospective clinical samples. Of the 22 samples with NIPS results of "no call", 17 samples were reclassified as "unaffected" (9 cases of chr13, 5 cases of chr18, and 3 cases of chr21); 2 samples remained classified as "no call" (1 case of chr18 and 1 case of chr21); and 3 samples were identified as T21 by iNIPS. The average increase in abundance of cfDNA fragments of 125-135 bp was 2.5 times, and the average decrease in maternal background interference was 1.3 times. On this basis, the detection of fetal aneuploidy was highly improved with the fetal fraction as low as 2%; iNIPS achieved 100% sensitivity and 99.90% specificity in retrospective samples. [ABSTRACT FROM AUTHOR]