A 2–3-year resolution record of stalagmite oxygen isotope variations from the south flank of the Qinling Mountains, central China, has revealed the Asian summer monsoon (ASM) precipitation variations ...in the investigated area over the past 750
years. The summer monsoon precipitation gradually increased since 1249
AD, reaching its highest values in the period 1535–1685
AD, and then decreased with substantial decadal- to centennial-scale fluctuations. The monsoon precipitation increased again between 1920 and 1970
AD. Three intervals of high monsoon precipitation were identified: 1535–1685
AD, 1755–1835
AD, and 1920–1970
AD. Three intervals of low precipitation were inferred in 1249–1325
AD, 1390–1420
AD, and 1890–1915
AD. The
δ
18O composition and lithological features of the stalagmite coincidently indicate a wetter climate during the Little Ice Age (LIA), which is also confirmed by climate records from Chinese historical documents within this area. A comparison with other high-resolution speleothem records indicates regional differences in monsoon precipitation variability from the south to the north of central China in the last 750
years on decadal- to centennial-scale. Power spectrum analysis of the
δ
18O record shows significant 117.8-, 34.6-, 14-, 10.3-, and ~
6-year periodicities. These periodicities are widely observed in the climate records from ASM-controlled areas of China and are consistent with the Gleissburg periodicity, Brϋckner periodicity, sunspot periodicity of solar activity, and El Nińo–Southern Oscillation (ENSO) periodicity. These correlations suggest that both solar activity and ENSO periodicity may have had important influences on ASM precipitation in China over the past 750
years.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cinnamaldehyde, cinnamyl alcohol, β-methylstyrene and cinnamic acid are four important biomass 3-phenyl-2-propene compounds. In the field of perfume and organic synthesis, their thermal stability and ...oxidation pathways deserve attention. This paper reports a new attempt to investigate the thermal stability and reactivity by a custom-designed mini closed pressure vessel test (MCPVT). The pressure and temperature behaviors were measured by MCPVT under nitrogen and oxygen atmosphere. The temperature of initial oxygen absorption (
T
a
) and rapid oxidation (
T
R
) were calculated. The results showed that four 3-phenyl-2-propene compounds were stable under nitrogen atmosphere. The
T
a
of cinnamaldehyde, cinnamyl alcohol, β-methylstyrene, and cinnamic acid was 271.25 K, 292.375 K, 323.125 K, and 363.875 K, and their
T
R
was 301.125 K, 332.75 K, 357.91 K, and 385.375 K, respectively. The oxidation reactivity order was derived to be cinnamaldehyde > cinnamyl alcohol > β-methylstyrene > cinnamic acid. The oxidation kinetics were determined using
n versus
time (
n
-
t
) plots, which showed a second-order reaction. Peroxide was determined by iodimetry, and the oxidation products were analyzed by gas chromatography-mass spectrometry (GC-MS). The results showed that the peroxide value of cinnamaldehyde, cinnamyl alcohol, β-methylstyrene, and cinnamic acid reached 18.88, 15.07, 9.62, and 4.24 mmol kg
−1
at 373 K for 6 h, respectively. The common oxidation products of four 3-phenyl-2-propene compounds were benzaldehyde, benzoic acid, and epoxide, which resulted from the carbon-carbon double bond oxidation. The substituents' oxidation products were obtained from the oxidation of cinnamaldehyde, cinnamyl alcohol, and β-methylstyrene. In particular, the difference is that no oxidation products of the carboxyl group of cinnamic acid were detected. The common oxidation products of the four 3-phenyl-2-propene compounds were benzaldehyde, benzoic acid, and epoxide, which resulted from the carbon-carbon double bond oxidation. The substituents' oxidation products were caught in the oxidation of cinnamaldehyde, cinnamyl alcohol, and β-methylstyrene. In particular, the difference is that no oxidation products of the carboxyl group of cinnamic acid were detected. According to the complex oxidation products, important insights into the oxidation pathways were provided.
A new attempt to investigate the thermal stability and reactivity of four 3-phenyl-2-propene compounds with oxygen by MCPVT has been reported.
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IJS, KILJ, NUK, UL, UM, UPUK
Bronchial carcinoids are neuroendocrine tumors that present as typical (TC) and atypical (AC) variants, the latter being more aggressive, invasive and metastatic. Studies of tumor initiating cell ...(TIC) biology in bronchial carcinoids has been hindered by the lack of appropriate in-vitro and xenograft models representing the bronchial carcinoid phenotype and behavior.
Bronchial carcinoid cell lines (H727, TC and H720, AC) were cultured in serum-free growth factor supplemented medium to form 3D spheroids and serially passaged up to the 3rd generation permitting expansion of the TIC population as verified by expression of stemness markers, clonogenicity in-vitro and tumorigenicity in both subcutaneous and orthotopic (lung) models. Acetazolamide (AZ), sulforaphane (SFN) and the AZ + SFN combination were evaluated for targeting TIC in bronchial carcinoids.
Data demonstrate that bronchial carcinoid cell line 3rd generation spheroid cells show increased drug resistance, clonogenicity, and tumorigenic potential compared with the parental cells, suggesting selection and expansion of a TIC fraction. Gene expression and immunolabeling studies demonstrated that the TIC expressed stemness factors Oct-4, Sox-2 and Nanog. In a lung orthotopic model bronchial carcinoid, cell line derived spheroids, and patient tumor derived 3rd generation spheroids when supported by a stroma, showed robust tumor formation. SFN and especially the AZ + SFN combination were effective in inhibiting tumor cell growth, spheroid formation and in reducing tumor formation in immunocompromised mice.
Human bronchial carcinoid tumor cells serially passaged as spheroids contain a higher fraction of TIC exhibiting a stemness phenotype. This TIC population can be effectively targeted by the combination of AZ + SFN. Our work portends clinical relevance and supports the therapeutic use of the novel AZ+ SFN combination that may target the TIC population of bronchial carcinoids.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We study spin-dependent electron transport properties of two dimensional graphene double and triple barrier junctions via first-principles calculations. The double barrier junction consists of two ...graphene leads, a quantum well of zigzag graphene nanoribbon (ZGNR) in the center, and two vacuum barriers separating the ZGNR from the two leads. Resonant electron tunneling occurs when the energy bands of graphene and ZGNR are well aligned in energy and wavevector. Highly spin-polarized electron transmission arises in such junctions when the two edges of the center ZGNR are in the ferromagnetic configuration. The spin polarization of the electron transmission at the Fermi energy can be tuned by gate voltage. We further investigate the dependence of the electron transmission on the width of the ZGNR, effects on barrier height when replacing vacuum by h-BN, and the consequence of replacing a double barrier by a triple barrier.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Total knee arthroplasty (TKA) is a mature procedure recommended for correcting knee osteoarthritis deformity, relieving pain, and restoring normal biomechanics. Although TKA is a successful and ...cost-effective procedure, patient dissatisfaction is as high as 50%. Knee pain after TKA is a significant cause of patient dissatisfaction; the most common location for residual pain is the anterior region. Between 4% and 40% of patients have anterior knee pain (AKP).
To investigate the effect of various TKA procedures on postoperative AKP.
We searched PubMed, EMBASE, and Cochrane from January 2000 to September 2022. Randomized controlled trials with one intervention in the experimental group and no corresponding intervention (or other interventions) in the control group were collected. Two researchers independently read the title and abstract of the studies, preliminarily screened the articles, and read the full text in detail according to the selection criteria. Conflicts were resolved by consultation with a third researcher. And relevant data from the included studies were extracted and analyzed using Review Manager 5.4 software.
There were 25 randomized controlled trials; 13 were comparative studies with or without patellar resurfacing. The meta-analysis showed no significant difference between the experimental and control groups (
= 0.61). Six studies were comparative studies of circumpatellar denervation
non-denervation, divided into three subgroups for meta-analysis. The two-subgroup meta-analysis showed no significant difference between the experimental and the control groups (
= 0.31,
= 0.50). One subgroup meta-analysis showed a significant difference between the experimental and control groups (
= 0.001). Two studies compared fixed-bearing TKA and mobile-bearing TKA; the results meta-analysis showed no significant difference between the experimental and control groups (
= 0.630). Two studies compared lateral retinacular release
non-release; the meta-analysis showed a significant difference between the experimental and control groups (
= 0.002); two other studies compared other factors.
Patellar resurfacing, mobile-bearing TKA, and fixed-bearing TKA do not reduce the incidence of AKP. Lateral retinacular release can reduce AKP; however, whether circumpatellar denervation can reduce AKP is controversial.
Noninvasive cell tracking in vivo has the potential to advance stem cell-based therapies into the clinic. Magnetic resonance imaging (MRI) provides an excellent image-guidance platform; however, ...existing MR cell labeling agents are fraught with limited specificity. To address this unmet need, we developed a highly efficient manganese porphyrin contrast agent, MnEtP, using a two-step synthesis. In vitro MRI at 3 Tesla on human embryonic stem cells (hESCs) demonstrated high labeling efficiency at a very low dose of 10
M MnEtP, resulting in a four-fold lower
relaxation time. This extraordinarily low dose is ideal for labeling large cell numbers required for large animals and humans. Cell viability and differentiation capacity were unaffected. Cellular manganese quantification corroborated MRI findings, and the agent localized primarily on the cell membrane. In vivo MRI of transplanted hESCs in a rat demonstrated excellent sensitivity and specificity of MnEtP for noninvasive stem cell tracking.
Drug-drug interaction events influence the effectiveness of drug combinations and can lead to unexpected side effects or exacerbate underlying diseases, jeopardizing patient prognosis. Most existing ...methods are restricted to predicting whether two drugs interact or the type of drug-drug interactions, while very few studies endeavor to predict the specific risk levels of side effects of drug combinations.
In this study, we propose MathEagle, a novel approach to predict accurate risk levels of drug combinations based on multi-head attention and heterogeneous attribute graph learning. Initially, we model drugs and three distinct risk levels between drugs as a heterogeneous information graph. Subsequently, behavioral and chemical structure features of drugs are utilized by message passing neural networks and graph embedding algorithms, respectively. Ultimately, MathEagle employs heterogeneous graph convolution and multi-head attention mechanisms to learn efficient latent representations of drug nodes and estimates the risk levels of pairwise drugs in an end-to-end manner.
To assess the effectiveness and robustness of the model, five-fold cross-validation, ablation experiments, and case studies were conducted. MathEagle achieved an accuracy of 85.85 % and an AUC of 0.9701 on the drug risk level prediction task and is superior to all comparative models. The MathEagle predictor is freely accessible at http://120.77.11.78/MathEagle/.
The experimental results indicate that MathEagle can function as an effective tool for predicting accurate risk of drug combinations, aiding in guiding clinical medication, and enhancing patient outcomes.
•MathEagle predicts specific risk levels for side effects of drug combinations.•Structural and behavioral characterization of drugs improves DDIE prediction performance.•Rigorous experiments demonstrate MathEagle's predictive ability, and easy-to-use online service is provided.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The climate variability during Dansgaard-Oeschger (D-O) events 19 to 25 (first recognized in the Greenland ice cores) was recorded in the Asian monsoon region, but the climatological dynamic ...mechanism is still poorly understood. Here, we present a new 230Th absolute chronology and high-resolution record of the Asian summer monsoon (ASM) from 117 to 69 kyr B.P. based on 25 230Th ages, 803 oxygen and carbon isotopes, as well as 493 trace element ratios of the YYZ1 stalagmite from Yangzi Cave in Fengdu County, 120 km from Chongqing City, China. The δ18O record supports a strong ASM during marine isotope stages (MIS) 5a and 5c and a weak ASM during MIS 4, 5b, and 5d. Millennial-scale oscillations of D-O 19–25 were also recorded in our speleothem δ18O. Multiple environmental proxies, δ13C and trace element records of YYZ1 stalagmite can also reflect local climate and environmental changes. A drought event was clearly identified between 93.0 and 91.5 kyr B.P., referred to as the 92 kyr event, which exhibited a rapid and abrupt fluctuation (V-shaped) based on our multi-proxy results. We found that D-O 25 event was not obvious in our record and in other Chinese speleothem records. The D-O 25 event occurred within a period of decreasing North Hemisphere summer insolation (NHSI), which led to different climate backgrounds, e.g., the increase of ice volume and the corresponding weakening of the Northern Atlantic thermohaline circulation. Conversely, the D-O events within the high NHSI period or the warm stages (MIS5a, MIS5c) exhibited more obvious fluctuations than those in the low NHSI period or the cool stages (MIS5b, MIS5d). Thus, we suggest that the differences between D-O events are mainly related to the change of the ASM in response to variable NHSI. Furthermore, the ASM during D-O events was also influenced by climate variations in the Southern Hemisphere (SH) and low latitudes, which should not be ignored.
•Variations in Asian summer monsoon (ASM) during MIS 5 were reconstructed in multi-proxy speleothem records.•A drought event was identified in 92 ka.•Most stalagmites records in China showed smaller trends in δ18O changes of DO 25 event.•Weak DO events were related to environmental changes at lower latitudes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To evaluate the protective effect of baicalin against a Vibrio parahaemolyticus challenge, immune parameters were analyzed and RNA interference (RNAi) was performed in the present study. The results ...from challenge tests showed that the cumulative mortalities in the 200 and 400 mg/kg baicalin groups after challenge with V. parahaemolyticus were significantly lower than they were in the 100 mg/kg baicalin or control groups (p < .05); the relative percent of survival reached 71.4%. Macrobrachium rosenbergii injected with V. parahaemolyticus exhibited a significant increase in lysozyme (LZM) and inducible nitric oxide synthase levels as well as phagocytic activity because of the immune response, while after treatment with baicalin, these immune parameters were further enhanced. The gene expression levels of anti‐lipopolysaccharide factors (ALFs), LZM, relish, and crustin were increased after treatment with baicalin or challenge with V. parahaemolyticus. The results of RNAi experiments demonstrated that the expression of crustins (Cru2, Cru4, Cru5, and Cru8), ALFs (ALF1, ALF3, ALF4, and ALF5), lysozymes (Lys1 and Lys2), and relish were significantly elevated after V. parahaemolyticus challenge. After MrToll4 was knocked down by siRNA, the expression levels of antimicrobial peptides (AMPs), except relish and Cru4, were inhibited. However, after oral administration of 400 mg/kg baicalin, the expression levels of all these AMPs, except Cru2, Cru4, ALF3, and relish, were upregulated.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Drug-resistant
Mycobacterium tuberculosis
(
M. tuberculosis
) has become an increasingly serious public health problem and has complicated tuberculosis (TB) treatment. Levofloxacin (LOF) is an ideal ...anti-tuberculosis drug in clinical applications. However, the detailed molecular mechanisms of LOF-resistant
M. tuberculosis
in TB treatment have not been revealed. Our study performed transcriptome and methylome sequencing to investigate the potential biological characteristics of LOF resistance in
M. tuberculosis
H37Rv. In the transcriptome analysis, 953 differentially expressed genes (DEGs) were identified; 514 and 439 DEGs were significantly downregulated and upregulated in the LOF-resistant group and control group, respectively. The KEGG pathway analysis revealed that 97 pathways were enriched in this study. In the methylome analysis, 239 differentially methylated genes (DMGs) were identified; 150 and 89 DMGs were hypomethylated and hypermethylated in the LOF-resistant group and control group, respectively. The KEGG pathway analysis revealed that 74 pathways were enriched in this study. The overlap study suggested that 25 genes were obtained. It was notable that nine genes expressed downregulated mRNA and upregulated methylated levels, including
pgi
,
fadE4
,
php
,
cyp132
,
pckA
,
rpmB1
,
pfkB
,
acg
, and
ctpF
, especially
cyp132
,
pckA
, and
pfkB
, which were vital in LOF-resistant
M. tuberculosis
H37Rv. The overlapping genes between transcriptome and methylome could be essential for studying the molecular mechanisms of LOF-resistant
M. tuberculosis
H37Rv. These results may provide informative evidence for TB treatment with LOF.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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