Ba4B14O25: A Deep Ultraviolet Transparent Nonlinear Optical Crystal with Strong Second Harmonic Generation Response Achieved by a Boron-Rich Closed-Loop Strategy.

Discovering new deep ultraviolet (DUV) nonlinear optical (NLO) materials is the current research hotspot. However, how to perfectly integrate several stringent performances into a crystal is a great challenge because of the natural incompatibility among them, particularly wide band gap and large NLO coefficient. To tackle the challenge, a boron-rich closed-loop strategy is supposed, based on which a new barium borate, Ba4B14O25, is designed and synthesized successfully via the high-temperature solid-state melting method. It features a highly polymeric 3D geometry with the closed-loop anionic framework [B14O25]8- constructed by the fundamental building blocks [B14O33]24-. The high-density π-conjugated [BO3]3- groups and the fully closed-loop B-O-B connections make Ba4B14O25 possess excellent NLO properties, including short UV cutoff edge (<200 nm), large second harmonic generation response (3.0 × KDP) and phase-matching capability, being a promising DUV-transparent NLO candidate material. The work provides a creative design strategy for the exploration of DUV NLO crystals.

A vector projection similarity-based method for miRNA-disease association prediction.

[S U M M A R Y] Many miRNA-disease association prediction models incorporate Gaussian interaction profile kernel similarity (GIPS). However, the GIPS fails to consider the specificity of the miRNA-disease association matrix, where matrix elements with a value of 0 represent miRNA and disease relationships that have not been discovered yet. To address this issue and better account for the impact of known and unknown miRNA-disease associations on similarity, we propose a method called vector projection similarity-based method for miRNA-disease association prediction (VPSMDA). In VPSMDA, we introduce three projection rules and combined with logistic functions for the miRNA-disease association matrix and propose a vector projection similarity measure for miRNAs and diseases. By integrating the vector projection similarity matrix with the original one, we obtain the improved miRNA and disease similarity matrix. Additionally, we construct a weight matrix using different numbers of neighbors to reduce the noise in the similarity matrix. In performance evaluation, both LOOCV and 5-fold CV experiments demonstrate that VPSMDA outperforms seven other state-of-the-art methods in AUC. Furthermore, in a case study, VPSMDA successfully predicted 10, 9, and 10 out of the top 10 associations for three important human diseases, respectively, and these predictions were confirmed by recent biomedical resources.

A Deep Learning Application of Capsule Endoscopic Gastric Structure Recognition Based on a Transformer Model.

BACKGROUND: Gastric structure recognition systems have become increasingly necessary for the accurate diagnosis of gastric lesions in capsule endoscopy. Deep learning, especially using transformer models, has shown great potential in the recognition of gastrointestinal (GI) images according to self-attention. This study aims to establish an identification model of capsule endoscopy gastric structures to improve the clinical applicability of deep learning to endoscopic image recognition. METHODS: A total of 3343 wireless capsule endoscopy videos collected at Nanfang Hospital between 2011 and 2021 were used for unsupervised pretraining, while 2433 were for training and 118 were for validation. Fifteen upper GI structures were selected for quantifying the examination quality. We also conducted a comparison of the classification performance between the artificial intelligence model and endoscopists by the accuracy, sensitivity, specificity, and positive and negative predictive values. RESULTS: The transformer-based AI model reached a relatively high level of diagnostic accuracy in gastric structure recognition. Regarding the performance of identifying 15 upper GI structures, the AI model achieved a macroaverage accuracy of 99.6% (95% CI: 99.5-99.7), a macroaverage sensitivity of 96.4% (95% CI: 95.3-97.5), and a macroaverage specificity of 99.8% (95% CI: 99.7-99.9) and achieved a high level of interobserver agreement with endoscopists. CONCLUSIONS: The transformer-based AI model can accurately evaluate the gastric structure information of capsule endoscopy with the same performance as that of endoscopists, which will provide tremendous help for doctors in making a diagnosis from a large number of images and improve the efficiency of examination.

LUNCRW: Prediction of potential lncRNA-disease associations based on unbalanced neighborhood constraint random walk.

Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are associated with various complex human diseases. They can serve as disease biomarkers and hold considerable promise for the prevention and treatment of various diseases. The traditional random walk algorithms generally exclude the effect of non-neighboring nodes on random walking. In order to overcome the issue, the neighborhood constraint (NC) approach is proposed in this study for regulating the direction of the random walk by computing the effects of both neighboring nodes and non-neighboring nodes. Then the association matrix is updated by matrix multiplication for minimizing the effect of the false negative data. The heterogeneous lncRNA-disease network is finally analyzed using an unbalanced random walk method for predicting the potential lncRNA-disease associations. The LUNCRW model is therefore developed for predicting potential lncRNA-disease associations. The area under the curve (AUC) values of the LUNCRW model in leave-one-out cross-validation and five-fold cross-validation were 0.951 and 0.9486 ± 0.0011, respectively. Data from published case studies on three diseases, including squamous cell carcinoma, hepatocellular carcinoma, and renal cell carcinoma, confirmed the predictive potential of the LUNCRW model. Altogether, the findings indicated that the performance of the LUNCRW method is superior to that of existing methods in predicting potential lncRNA-disease associations.

Activated AMPK Protects Against Chronic Cerebral Ischemia in Bilateral Carotid Artery Stenosis Mice.

AMP-activated protein kinase (AMPK) is a regulator of cellular energy metabolism. Long-term use of metformin, an AMPK activator, was previously reported to be neuroprotective, as it promotes behavioral improvement and angiogenesis following an acute ischemic injury of the brain. However, only a few studies have demonstrated the role of AMPK in alleviating chronic cerebral ischemia (CCI) in mice models in the long-term (over 3 months). Therefore, we established a mouse model of CCI via bilateral carotid artery stenosis (BCAS) to explore the effect of AMPK on CCI. We used four groups of 3-month-old male C57BL/6 mice labeled as Sham, BCAS, BCAS + metformin treatment (BCAS + Met) and BCAS + AMPKα2 gene knockout (BCAS + KO). Three months after BCAS, we measured the AMPK protein expression, spatial learning and memory, Nissl bodies, cell apoptosis, astrocyte activation, and oligodendrocyte maturation. Additionally, we observed the brain tissues for changes in cell morphology. We observed that mice in the BCAS group had impaired spatial learning and memory compared with those in the sham group. The brain tissues of mice with CCI injury showed altered cell morphology, fewer Nissl bodies, cerebral cells apoptosis, and astrocyte activation. Interestingly, compared with mice from the BCAS group, the brains of mice from BCAS + Met group suffered lesser damage, whereas those of mice from the BCAS + KO group suffered more damage. The activation of AMPK, especially AMPKα2, plays a neuroprotective role during CCI in a mouse model of BCAS.

Acute bilateral multiple subcortical infarcts as manifestation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterised by recurrent subcortical ischemic events, migraine with aura, dementia and mood disturbance. Strokes are typically lacunar infarcts; however, bilateral multiple subcortical lacunar infarcts have been described only sporadically. METHOD: We described four CADASIL patients who presented with acute bilateral multiple subcortical infarcts as the first manifestation. We also briefly summarised the case reports detailing the bilateral multiple infarcts in CADASIL. RESULTS: Patient 1 and patient 2 were family members, and they presented with cognitive impairment. Patient 3 and patient 4 presented with slurred speech and hemiparesis. Patients 1, 3 and 4 developed hemodynamic fluctuations before the occurrence of ischemic stroke. Laboratory tests revealed elevated fibrinogen levels in patients 3 and 4. The brain magnetic resonance imaging showed acute bilateral multiple subcortical infarcts on the periventricular white matter in all the patients. CONCLUSION: CADASIL, with a poor brain hemodynamic reserve, is vulnerable to hemodynamic alterations (e.g. blood pressure fluctuation, dehydration, blood loss and anaemia) and intolerable to ischemia and hypoxia of the brain. Furthermore, blood hypercoagulation may contribute to acute multiple bilateral infarctions in CADASIL. Therefore, it is necessary to avert these predispositions in CADASIL patients in their daily life.

A coupled awareness-epidemic model on a multi-layer time-varying network.

Social interactions have become more complicated and changeable under the influence of information technology revolution. We, thereby, propose a multi-layer activity-driven network with attractiveness considering the heterogeneity of activated individual edge numbers, which aims to explore the role of heterogeneous behaviors in the time-varying network. Specifically, three types of individual behaviors are introduced: (i) self-quarantine of infected individuals, (ii) safe social distancing between infected and susceptible individuals, and (iii) information spreading of aware individuals. Epidemic threshold is theoretically derived in terms of the microscopic Markov chain approach and the mean-field approach. The results demonstrate that performing self-quarantine and maintaining safe social distance can effectively raise the epidemic threshold and suppress the spread of diseases. Interestingly, individuals' activity and individuals' attractiveness have an equivalent effect on epidemic threshold under the same condition. In addition, a similar result can be obtained regardless of the activated individual edge numbers. The epidemic outbreak earlier in a situation of the stronger heterogeneity of activated individual edge numbers.

A New Hemoglobin Variant: Hb Tangshan [HBA1: c.239C > T, CD79(GCG > GTG)(Ala > Val)] Detected by MALDI-TOF MS.

In this report we decribed a new α-chain variant found during the measurement of hemoglobin A1c (Hb A1c) using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS). MALDI-TOF MS analysis detected an α-chain variant with a mass of 15,155 Da. However, this Hb variant was not detected during Hb A1c measurement by cation-exchange high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) methods. Sanger sequencing validated the presence of a heterozygous missense mutation [HBA1: c.239C > T, CD79(GCG > GTG)(Ala > Val)]. The observed 28 Da mass difference exactly matches the theoretical mass difference (28 Da) resulting from the substitution of alanine (89.079) with valine (117.133). As this represents the initial documentation of the mutation, we named it Hb Tangshan after the proband's residence.

The Expression Pattern and Clinical Significance of Lysyl Oxidase Family in Gliomas.

LOX (Lysyl oxidase) family participates in the catalysis of collagen and elastin to maintain ECM homeostasis. Glioma is the most common primary brain tumor and LOX family has not been systemic studied in glioma. In this study, we found LOX family members are upregulated expressed in gliomas samples. A protein-protein interaction network (PPIN) was construct to visualize and understand the differential expression pattern, as well as functional annotation, for LOX family and their interacting proteins, which involved in collagen fibril organization and MAPK signaling pathway. Through subcellular localization distribution, the LOX family members distribute both intracellular and extracellular. All five LOX members are consistently significantly correlate with dendritic cell both in immune infiltrate of GBM and LGG. Survival analysis showed that high expression of LOX family is associated with a poor prognosis of gliomas patients. These analyses provide important clues to identify the potential biological roles for LOX family in gliomas, which might serve as diagnosis markers.

Protective effects of Gypenoside XVII against cerebral ischemia/reperfusion injury via SIRT1-FOXO3A- and Hif1a-BNIP3-mediated mitochondrial autophagy.

BACKGROUND: Mitochondrial autophagy maintains mitochondrial function and cellular homeostasis and plays a critical role in the pathological process of cerebral ischemia/reperfusion injury (CIRI). Whether Gypenoside XVII (GP17) has regulatory effects on mitochondrial autophagy against CIRI remains unclear. The purpose of this study was to investigate the pharmacodynamic effects and mechanisms of GP17 on mitochondrial autophagy after CIRI. METHODS: A rat middle cerebral artery occlusion/reperfusion (MCAO/R) model was used to assess the effects of GP17 against CIRI and to explore the underlying mechanisms. An oxygen-glucose deprivation/reoxygenation (OGD/R) cell model was used to verify the ameliorative effects on mitochondrial damage and to probe the autophagy pathways involved in combating neural injuries. RESULTS: The in vivo results showed that GP17 significantly improved mitochondrial metabolic functions and suppressed cerebral ischemic injury, possibly via the autophagy pathway. Further research revealed that GP17 maintains moderate activation of autophagy under ischemic and OGD conditions, producing neuroprotective effects against CIRI, and that the regulation of mitochondrial autophagy is associated with crosstalk between the SIRT1-FOXO3A and Hif1a-BNIP3 signalling pathway that is partially eliminated by the specific inhibitors AGK-7 and 2-ME. CONCLUSION: Overall, this work offers new insights into the mechanisms by which GP17 protects against CIRI and highlights the potential of therapy with Notoginseng leaf triterpene compounds as a novel clinical strategy in humans.

Ba6Zn6(B3O6)6(B6O12): Barium Zinc Borate Contains π-Conjugated [B3O6]3- Anions and [B6O12]6- Anion with Edge-Sharing BO4 Tetrahedra.

A novel barium zinc borate contains π-conjugated [B3O6]3- anions and [B6O12]6- anion with edge-sharing BO4 tetrahedra, Ba6Zn6(B3O6)6(B6O12), has been successfully synthesized via a high-temperature solution reaction. In its structure, the isolated planar π-conjugated B3O6 groups are interconnected by ZnO4 tetrahedra via corner sharing to construct a [Zn3(B3O6)3]3- single layer parallel to the ab plane with the large Zn3B6 9-member rings. Two adjacent [Zn3(B3O6)3]3- single layers are interconnected by [B6O12]6- anions into a two-dimensional [Zn6(B3O6)6(B6O12)]12- double layer with 1D tunnels of Zn4B8 12-member rings along the a-axis. Neighboring such double layers are packed in an A-B-A-B... fashion along the c axis, and the Ba2+ ions act as counterbalance cations filling in the voids of double layers. All of the planar π-conjugated [B3O6]3- groups in Ba6Zn6(B3O6)6(B6O12) are in approximately parallel arrangement, producing large optical anisotropy and birefringence. The UV-vis-NIR absorption spectrum manifests that the UV cutoff edge for the title compound is below 200 nm. Ba6Zn6(B3O6)6(B6O12) possesses the largest birefringence (0.115@1064 nm) among the zincoborates reported. Its thermal stability, infrared spectrum, and theoretical calculations were also performed.

NaBa3[M2B7O16(OH)2]F2 (M = Ge, Si): Two Synthetic F Analogues of Garrelsite with [B7O16(OH)2]13- Polyanions and Deep-Ultraviolet Cutoff Edges.

Two new borogermanate/borosilicate fluorides, namely, NaBa3[M2B7O16(OH)2]F2 (M = Ge, Si), have been successfully synthesized through a conventional mild hydrothermal method. They represent the first examples of mixed alkali and alkaline-earth borogermanate/borosilicate fluorides. NaBa3[M2B7O16(OH)2]F2 (M = Ge, Si) crystallize in the space group of C2/c, and their structures feature a unique 3D anionic framework composed of [B7O16(OH)2]13- polyanions corner-sharing with SiO4 or GeO4 tetrahedra, forming 1D 10-membered-ring tunnels along the b axis, which are filled by Na+, Ba2+, and F- ions. UV-vis-near-IR absorption spectra identify the title compounds possessing short deep-ultraviolet absorption edges (below 200 nm), while their birefringences were calculated to be 0.021 and 0.016 at 1064 nm, respectively. Optical property, thermal stability, and theoretical calculations have also been conducted on NaBa3[M2B7O16(OH)2]F2 (M = Ge, Si).

Use of Capillary Electrophoresis Migration Position for the Presumptive Identification of Hemoglobin Variants Prevalent in China.

Capillary electrophoresis (CE) is increasingly being used to screen for hemoglobinopathies. We here report the migration position of hemoglobin (Hb) variants prevalent in China determined by CE. The CE migration position showed excellent precision and minor inter-individual variation. We conclude that the CE migration position can be used as a reliable indicator for identifying Hb variants and can also help to establish a well-characterized library of Hb variants for their refined presumptive identification.

Bi2[B2(SeO3)6]: A Metal Boroselenite with a Unique Zero-Dimensional [B2(SeO3)6]6- Anionic Group and Large Birefringence.

Explorations of new types of borates are important because of their promising application in diverse fields. A new bismuth-containing boroselenite, Bi2[B2(SeO3)6], has been obtained through high-temperature solid-state reaction in a closed system. Bi2[B2(SeO3)6] possesses a zero-dimensional [B2(SeO3)6]6- anionic group that does not belong to any types of reported boroselenites. Besides, Bi2[B2(SeO3)6] is the first boroselenite with lone-pair electrons containing a metal ion as the countercation. More interestingly, on the basis of the first-principles calculations, this compound displays a large birefringence (0.090) at 1064 nm.

Hb Jishui [HBA1: c.225C>G, Codon 74 (GAC>GAG), Asp→Glu]: A Novel α Chain Hemoglobin Variant Detected During Hb A1c Measurement.

Here we report a novel α chain hemoglobin (Hb) variant found in a 74-year-old Chinese male. We accidentally discovered this Hb variant during the measurement of Hb A1c by a capillary electrophoresis (CE) method (Hb A1c program, CapillaryS3 TERA). However, Hb analysis with the Hb program of CapillaryS3 TERA and the VARIANT II™ ß-Thalassemia Short Program showed no indication of the Hb variant. Sanger sequencing revealed a new missense mutation on the HBA1 gene [HBA1: c.225C>G, codon 74 (GAC>GAG), Asp→Glu]. We named it Hb Jishui after the birthplace of the proband.

A Novel α-Globin Chain Variant, Hb Nanchang [HBA2: c.46G>A, Codon 15 (GGT>AGT) (Gly→Ser)], Detected by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.

Here we report a new α chain variant accidentally discovered during Hb A1c measurement by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) that revealed the presence of a variant α chain with a mass of 15155 Da. However, this hemoglobin (Hb) variant cannot be detected by the first-line methods such as cation exchange high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Sanger sequencing confirmed the presence of a heterozygous missense mutation [HBA2: c.46G>A, codon 15 (GGT>AGT), (Gly→Ser)]. The theoretical mass difference (30 Da) due to the substitution of amino acid glycine to serine matched the actual measured mass difference (29 Da). As this is the first report of the mutation, we named it Hb Nanchang after the place of residence of the proband.

Broad-Band Excited and Tunable Luminescence of CaTbAl3O7:RE3+ (RE3+ = Ce3+ and/or Eu3+) Nanocrystalline Phosphors for Near-UV WLEDs.

Here, we demonstrate a novel donor-intermediate-receptor energy transfer model through a Ce3+ → Tb3+ → Eu3+ scheme in a CaTbAl3O7:Ce3+,Eu3+ nanocrystalline phosphor. A new type of CaTbAl3O7 and CaTbAl3O7:RE3+ (RE3+ = Ce3+ and/or Eu3+) nanocrystalline phosphors were prepared by a simple sol-gel method. There exist efficient energy transfers of Ce3+ → Tb3+, Tb3+ → Eu3+, and Ce3+ → Tb3+ → Eu3+ in CaTbAl3O7:RE 3+ (RE 3+ = Ce3+ and/or Eu3+) nanocrystalline phosphors. With near-UV or UV light excitation, the as-prepared CaTbAl3O7:RE 3+ (RE 3+ = Ce3+ and/or Eu3+) nanocrystalline phosphors' luminous color can be regulated from green to green-yellow, yellow, orange, and orange-red by adjusting the doping concentration, categories, and different proportions of codoping Ce3+ to Eu3+ ions in the CaTbAl3O7 matrix. The luminescence mechanism with respect to the CaTbAl3O7:RE3+ (RE3+ = Ce3+ and/or Eu3+) nanocrystalline phosphors has been tentatively proposed. Due to their excellent luminescence properties, the as-prepared CaTbAl3O7, CaTbAl3O7:Ce3+, CaTbAl3O7:Eu3+, and CaTbAl3O7:Ce3+,Eu3+ nanocrystalline phosphors exhibit bright prospects in NUV-LEDs and other photoelectric field.

Hemoglobin variants in southern China: results obtained during the measurement of glycated hemoglobin in a large population.

Objectives: Hemoglobin (Hb) variant is one of the most common monogenic inherited disorders. We aimed to explore the prevalence and hematological and molecular characteristics of Hb variants in southern China. Methods: We collected blood samples from all patients with suspected variants found during HbA1c measurement via a cation-exchange high-performance liquid chromatography system (Bio-Rad Variant II Turbo 2.0) or a capillary electrophoresis method (Sebia Capillarys). Hematological analysis, Sanger sequencing, and gap-PCR were performed for these samples. Results: Among the 311,024 patients tested, we found 1,074 Hb variant carriers, including 823 identified using Capillarys and 251 using Variant II Turbo 2.0, with a total carrier rate of 0.35%. We discovered 117 types of Hb variants (52 HBB, 47 HBA, and 18 HBD mutations) containing 18 new mutations. The most common variant found was Hb E, followed by Hb New York, Hb J-Bangkok, Hb Q-Thailand, Hb G-Coushatta, Hb G-Honolulu, Hb G-Taipei, and Hb Broomhill. Most heterozygotes for the Hb variant exhibited normal hematological parameters. However, most patients with compound heterozygotes for the Hb variant and thalassemia showed varied degrees of microcytic hypochromic anemia. Conclusions: The prevalence of hemoglobin variants remains high and exhibits genetic diversity and widespread distribution in the population of southern China.

Potential of MALDI-TOF mass spectrometry to overcome the interference of hemoglobin variants on HbA1c measurement.

Objectives: Hemoglobin (Hb) variants remain an important cause of erroneous HbA1c results. We present an approach to overcome the interference of Hb variants on HbA1c measurements using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Methods: Samples containing or not containing Hb variants were analyzed for HbA1c using an MALDI-TOF MS system (QuanTOF) and a boronate affinity comparative method (Ultra2). For QuanTOF, two sets of HbA1c values were obtained through α- and ß-chain glycation. Results: A robust correlation between the glycation degrees of the α- and ß-chains was found, and HbA1c values derived from α- and ß-chain glycation correlated well with the Ultra2 results. Statistically significant differences (p<0.01) were found for all the Hb variants tested. When using the conventional ß-chain glycation to determine HbA1c, clinically significant differences were only found among samples containing ß-chain variants detected by QuanTOF (i.e., Hb J-Bangkok, Hb G-Coushatta, and Hb G-Taipei). In contrast, based on α-chain glycation, no clinically significant differences were found for these three variants. Conclusions: In addition to conventional ß-chain glycation, α-chain glycation can be used to calculate HbA1c values. The interference of Hb variants on HbA1c quantification can be overcome by employing the glycation of the globin chain without a genetic variant to estimate HbA1c values.

Identification of a new hemoglobin variant Hb Liuzhou [HBA1:C.182A→G] by MALDI-TOF mass spectrometry during HbA1c measurement.

Structural hemoglobin (Hb) variant is generally caused by a point mutation in the globin gene that produces one amino acid substitution. Here, we describe a new α-chain variant found during HbA1c measurement. HbA1c procedures based on both ion-exchange high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) techniques failed to identify its presence. In contrast, MALDI-TOF mass spectrometry (MS) revealed the existence of a variant α-chain with a mass of 15155 Da. In addition, the Hb variant interfered with HbA1c determined by Bio-Rad D100. DNA sequencing confirmed the occurrence of a new heterozygous mutation [HBA1:C.182A→G] at codon 60, resulting in a coding change from lysine to arginine. We named it Hb Liuzhou for thde birthplace of the patient. This case exemplified that MALDI-TOF mass spectrometry can serve as the method of choice to identify and quantify the Hb variant.