Modifying effects of green space on the relationships between air pollution and ischemic cerebrovascular event recurrence in Tianjin, China.

This study aimed to explore how air pollution and green space influence ICE recurrence and whether they might interact with each other. A case-cross design was used in this study, which was carried out in Tianjin, China. A total of 8306 patients with recurrent ICE were collected from 2019 to 2020. The maximum effects of PM2.5, PM10, SO2, NO2, CO were 1.012 (95%CI: 1.004, 1.019), 1.010 (95%CI: 1.004, 1.016), 1.035 (95%CI: 0.982, 1.091), 1.067 (95%CI: 1.043, 1.091) and 1.012 (95%CI: 1.004, 1.021) , respectively, and the risk was higher in males and in the 50-60 age group. In the stratification of greening, it was found that air pollution except O3 had the highest risk of ICE recurrence for those with lower green space. Our study found that air pollution (except O3) can increase the risk of ICE recurrence, and this risk can be reduced by increasing green space.

A Meta-Analysis of the Prevalence of Children Goiter in High Water Iodine Areas of China.

Although there are now a large number of studies confirming that high iodine levels can cause goiter, there is controversy and a lack of quantitative data. A systematic search of PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and China Biomedical Database for literature on high iodine and goiter in children was performed with a time limit from January 2013 to October 2023. After screening the literature based on the inclusion criteria, extracting the literature data, and evaluating the risk of bias of the included studies, a single-arm meta-analysis was performed using R 4.0.4 software. Twenty-three studies with a total of 50,980 subjects were included. Meta-analysis showed that the prevalence of goiter among children in water-borne iodine-excess areas was 6.0% [95% CI (4.3%, 7.6%)], and subgroup analyses showed that the prevalence of goiter in children with water iodine 100.1-150 µg/L, 150.1-300 µg/L, and > 300 µg/L was 7.5% [95% CI (0.0%, 15.8%)], 5.5% [95% CI (3.1%, 8.0%)], and 10.2% [95% CI (6.7%, 13.6%)], respectively, and the difference was statistically significant (P < 0.01); The prevalence of goiter among children in the northern China (5.8% [95% CI (4.1%, 7.5%)]) was higher than that in the southern China (3.5% [95% CI (1.0%, 6.0%)]) (P < 0.01); the prevalence of goiter in children with urinary iodine levels 100-199 µg/L, 200-299 µg/L, and ≥ 300 µg/L was 2.4% [95% CI (1.9%, 2.9%)], 3.3% [95% CI (1.9%, 4.8%)], and 7.3% [95% CI (4.4%, 9.9%)], respectively, the difference was statistically significant (P < 0.01); the prevalence of goiter in children aged 8, 9, 10, 11, and 12 years old was 5.1% [95% CI (3.9%, 6.4%)], 8.0% [95% CI (4.0%, 11.9%)], 6.2% [95% CI (3.9%, 8.5%)], 5.5% [95% CI (0.0%, 13.2%)], and 5.4% [95% CI (0.0%, 15.1%)], and when age ≥ 9 years, the relationship between goiter prevalence and age showed a trend toward decreasing with age, but the relationship between different age was no statistical difference in the prevalence of goiter between ages. urinary iodine. The prevalence of goiter in children was higher in areas with high water iodine; the prevalence of goiter in children in the north was significantly higher than that in the south; the prevalence of goiter in children tends to increase with increased urinary iodine levels.

How did we eliminate the hazards of water-borne excessive iodine in northern China?

Drinking water is the main cause of iodine excess among Chinese residents and we have found that water iodine concentration (WIC) reduction was the effective intervening measure. In this study, to eliminate the hazards of water-borne excessive iodine, we firstly investigated the WIC of villages in Tianjin in 2017 to determine the distribution range. Secondly, the risk characterization of excessive iodine on residents in 6∼< 9 years old, 9∼< 12 years old, 12∼< 15 years old, 15∼< 18 years old and adults were evaluated, and the safe upper limit of WIC was determined. Finally, WIC was investigated again after the completion of WIC reduction in water-borne excessive-iodine villages in 2020, and the differences in urinary iodine concentration (UIC) and thyroid volume (Tvol) of children aged 8-10 years before and after WIC reduction were analyzed. The WIC of 2459 villages surveyed was 22.30 (8.60-58.80) µg/L and the maximum was 514 µg/L. There were 422 villages with WIC > 100 µg/L. Under the conditions of non-iodized salt intake, recommended amount of iodized salt intake and actual amount intake, the maximum of excessive iodine exposure hazard quotient (HQ) were the highest in the age group of 6∼< 9 years, which were 2.300, 2.663 and 2.771, the safe upper WIC limits were 223 µg/L, 142 µg/L and 118 µg/L and villages with HQ> 1 accounted for 4.14%, 6.09% and 6.88% of all villages, respectively. After the WIC reduction, the WIC of the former water-borne iodine-excess villages decreased to < 100 µg/L, and the UIC and Tvol of children decreased (both P < 0.001) and was within normal range. Determining the distribution range of water-borne iodine-excess areas, exploring appropriate intervening measure, carrying out risk assessment, determining the WIC safe upper limit, intervening and evaluating the intervention effect can be the process to eliminate the hazards of water-borne excessive iodine.

Mitochondrial dysfunction and drug targets in multiple myeloma.

Multiple myeloma (MM) is the second most common hematological cancer that has no cure. Although currently there are several novel drugs, most MM patients experience drug resistance and disease relapse. The results of previous studies suggest that aberrant mitochondrial function may contribute to tumor progression and drug resistance. Mitochondrial DNA mutations and metabolic reprogramming have been reported in MM patients. Several preclinical and clinical studies have shown encouraging results of mitochondria-targeting therapy in MM patients. In this review, we have summarized our current understanding of mitochondrial biology in MM. More importantly, we have reviewed mitochondrial targeting strategies in MM treatment.

Reference Intervals for Thyroid Hormones and Thyroid Volume in Children Aged 7 ~ 13 Years from Iodine-Sufficient Areas in Tianjin, China.

Reference intervals (RIs) for serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) suitable for local children are urgently needed in northern China. The reference interval for thyroid volume (Tvol) in Chinese children also differed greatly from that recommended by the WHO. This study aimed to establish TSH, FT3, FT4, and Tvol RIs suitable for children in northern China. A total of 1070 children aged 7 ~ 13 were recruited from iodine nutrition-sufficient areas in Tianjin, China, from 2016 to 2021. Four hundred fifty-eight children aged 7 ~ 13 years, and 815 children aged 8 ~ 10 years were eventually included to study RIs for the thyroid hormones and Tvol. RIs for thyroid hormones were established in accordance with the Clinical Laboratory Standards Institute (CLSI) document C28-A3 guidelines. Quantile regression was used to analyze the influencing factors of Tvol. RIs for TSH, FT3, and FT4 were 1.23 (1.14 ~ 1.32) to 6.18 (5.92 ~ 7.26) mIU/L, 5.43 (5.29 ~ 5.52) to 7.89 (7.66 ~ 7.98) pmol/L, and 13.09 (12.85 ~ 13.73) to 22.22 (21.61 ~ 22.51) pmol/L. There was no need to establish RIs by age and gender. Our RIs could increase the prevalence of subclinical hyperthyroidism (P < 0.001) and reduce the prevalence of subclinical hypothyroidism (P < 0.001). Body surface area (BSA) and age are correlated with the 97th percentile of Tvol (both P < 0.001). Our reference interval could increase the goiter rate in children from 2.97 to 4.96% (P = 0.007). The thyroid hormones' reference intervals suitable for local children should be established. In addition, BSA and age should be considered when establishing Tvol reference interval.

Association between dental fluorosis prevalence and inflammation levels in school-aged children with low-to-moderate fluoride exposure.

Inflammation mediates the neurological deficits caused by fluoride. Thus, whether inflammation is the underlying mechanism of dental fluorosis (DF) in school-aged children is worth exploring. A cross-sectional study was conducted to investigate the association between inflammation and the prevalence and severity of DF with low-to-moderate fluoride exposure. Fasting morning urine and venous blood samples were collected from 593 children aged 7-14 years. The fluoride content in the water and urine samples was measured using a fluoride ion-selective electrode assay. The levels of interleukin-1ß (IL-1ß) and C-reactive protein (CRP) were detected using an enzyme-linked immunosorbent assay. The Dean's index was used when performing dental examinations. Regression, stratified, and mediation analyses were performed to analyze the association between fluoride exposure, inflammation, and DF prevalence. In the adjusted regression models, the prevalence of mild DF was 1.723-fold (95% confidence interval [CI]:1.612, 1.841) and 1.594-fold (1.479, 1.717) greater than that of normal DF for each 1 mg/L increase in water and urinary fluoride content, respectively. The prevalence of mild DF increased by 3.3% for each 1 pg/mL increase in the IL-1ß level and by 26.0% for each 1 mg/L increase in the CRP level. Stratified analysis indicated a weaker association between fluoride concentration and DF prevalence in boys than in girls, and susceptibility in the boys was reflected by the association of IL-1ß with very mild and moderate DF prevalence. For every 1 mg/L increase in water and urinary fluoride levels, the proportion of IL-1ß-mediated effects on the prevalence of mild DF was 10.0% (6.1%, 15.8%) and 8.7% (4.8%, 15.2%), respectively, and the proportion of CRP-mediated effects was 9.2% (5.5%, 14.9%) and 6.1% (3.3%, 11.0%), respectively. This study indicates that the DF prevalence may be sex-specific. Inflammatory factors may partially mediate the increased prevalence of mild DF in school-aged children with low-to-moderate fluoride exposure.

NiH-Catalyzed Proximal-Selective Hydroamination of Unactivated Alkenes with Anthranils.

The regioselective hydroamination of unactivated alkenes is a long-standing challenge in organic synthesis. Herein, we report a NiH-catalyzed proximal-selective hydroamination of unactivated alkenes with 8-aminoquinoline (AQ) as a bidentate auxiliary and anthranils as aminating reagents. A wide range of primary aryl amines bearing an ortho-carbonyl group were installed in both terminal and internal unactivated alkenes, delivering a variety of valuable ß- and γ-amino acid building blocks, respectively, with excellent regiocontrol. The utility of this transformation was further demonstrated by the conversion of the multifunctionalized aryl amines into useful N-heterocycles.

ISG20L2 suppresses bortezomib antimyeloma activity by attenuating bortezomib binding to PSMB5.

The proteasome inhibitors (PIs) bortezomib and carfilzomib, which target proteasome 20S subunit beta 5 (PSMB5) in cells, are widely used in multiple myeloma (MM) treatment. In this study, we demonstrated the role of interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2) in MM PI resistance. Gain- and loss-of-function studies showed that ISG20L2 suppressed MM cell sensitivity to PIs in vitro and in vivo. Patients with ISG20L2lo MM had a better response to PIs and a longer overall survival than patients with ISG20L2hi MM. Biotinylated bortezomib pull-down assays showed that ISG20L2 competed with PSMB5 in binding to bortezomib. The surface plasmon resonance assay confirmed the direct binding of bortezomib to ISG20L2. In ISG20L2hi MM cells, ISG20L2 attenuated the binding of bortezomib to PSMB5, resulting in lower inhibition of proteasome activity and therefore less bortezomib-induced cell death. Overall, we identified a potentially novel mechanism by which ISG20L2 conferred bortezomib resistance on MM. The expression of ISG20L2 correlated with MM PI responses and patient treatment outcomes.

Nutritional Value, Fermentation Characteristics and In Vitro Degradability of Whole Wheat Hay Harvested at Three Stages of Maturity.

The nutritional value of whole crop wheat hay (WCWH) harvested at different maturation stages are different, and its feeding effects on dairy cows have not been thoroughly evaluated. In this study, the in vitro digestibility of whole wheat (Nongda 22) hay harvested during the flowering, late milk and dough stages were evaluated using batch culture technique. The neutral detergent fiber (NDF) and acid detergent fiber (ADF) contents of whole wheat hay decreased by 35.5% and 40.4%, respectively, whereas the non-fibrous carbohydrates (NFC) content increased by 50.3% in WCWH harvested during the dough stage as compared to the flowering stage (p < 0.01). The pH of the fermentation liquid and acetate to propionate ratio was greatest in the wheat harvested during the flowering stage and lowest during the dough stage (p = 0.03), whereas the volatile fatty acid (VFA) concentration was greatest during the dough stage and lowest during the flowering stage (p < 0.01). The dry matter loss (DML) was 9.6% and 6.2% greater (p < 0.01) during the late milk stage than in the flowering or dough stages, and the NDF loss (NDFL; p = 0.01) and ADF loss (ADFL; p < 0.01) was greater in both the flowering and late milk stages. In conclusion, though the content of NDF was lower in the dough stage, and the starch to NFC ratio was greater, we determined that the optimal harvest stage should be the late milk stage due to the greater dry matter digestibility, the relatively greater NFC content and the shorter planting days.

High prevalence of colistin resistance and mcr-9/10 genes in Enterobacter spp. in a tertiary hospital over a decade.

Enterobacter spp. are members of the 'ESKAPE' group of pathogens, which which are recognised as the leading cause of multidrug-resistant (MDR) hospital-acquired infections. Colistin is usually regarded as a last-line therapeutic option for MDR Gram-negative bacilli infections. However, colistin-resistant Enterobacter spp. have emerged in the last decade. Here we investigated the prevalence of colistin resistance and mcr genes in Enterobacter spp. of clinical origin between 2011 and 2020 in a tertiary hospital in China. Colistin resistance rates ranged between 17.1% and 34.5%, with an overall prevalence of 22.2% (190/854). No mcr-1 to mcr-8 genes were identified in the colistin-resistant Enterobacter spp. isolates, while mcr-9 and mcr-10 were detected at rates of 8.4% (16/190) and 12.6% (24/190), respectively. All of the mcr-9/10-positive Enterobacter isolates belonged to the Enterobacter cloacae complex (ECC). Meanwhile, 14.8% (98/664) and 6.0% (40/664) of non-colistin-resistant Enterobacter spp. isolates carried mcr-9 and mcr-10 genes, respectively. For the 40 mcr-9/10-positive colistin-resistant ECC isolates, mcr-9-positive ECC isolates usually co-produced extended-spectrum ß-lactamases (ESBLs) or carbapenemases, while mcr-10-positive ECC isolates produced neither. Most mcr-9/10 genes were located on plasmids. The backbone of mcr-9-harbouring plasmids was conserved, while that of mcr-10-harbouring plasmids was diverse. Our findings revealed a high prevalence of colistin resistance and a silent distribution of mcr-9/10 genes in clinical Enterobacter spp. isolates in China. It is urgent to take steps and interventions to control the prevalence of colistin resistance and prevent the dissemination of mcr-9/10 genes.

ALCAM regulates multiple myeloma chemoresistant side population.

Drug-resistance is a major problem preventing a cure in patients with multiple myeloma (MM). Previously, we demonstrated that activated-leukocyte-cell-adhesion-molecule (ALCAM) is a prognostic factor in MM and inhibits EGF/EGFR-initiated MM clonogenicity. In this study, we further showed that the ALCAM-EGF/EGFR axis regulated the MM side population (SP)-mediated drug-resistance. ALCAM-knockdown MM cells displayed an enhanced ratio of SP cells in the presence of bone marrow stromal cells (BMSCs) or with the supplement of recombinant EGF. SP MM cells were resistant to chemotherapeutics melphalan or bortezomib. Drug treatment stimulated SP-genesis. Mechanistically, EGFR, primed with EGF, activated the hedgehog pathway and promoted the SP ratio; meanwhile, ALCAM inhibited EGFR downstream pro-MM cell signaling. Further, SP MM cells exhibited an increased number of mitochondria compared to the main population. Interference of the mitochondria function strongly inhibited SP-genesis. Animal studies showed that combination therapy with both an anti-MM agent and EGFR inhibitor gefitinib achieved prolonged MM-bearing mice survival. Hence, our work identifies ALCAM as a novel negative regulator of MM drug-resistance, and EGFR inhibitors may be used to improve MM therapeutic efficacy.

Iodine in household cooking salt no longer plays a crucial role in iodine status of residents in Tianjin, China.

PURPOSE: The contribution of household cooking salt to population iodine status is decreasing in China, the applicability of the coverage rate of iodized salt (IS), proportion of adequately iodized salt (AIS), and salt iodine concentration (SIC) of household cooking salt used for iodine status assessment of residents requires further investigation. METHODS: Through the IDD control project, 16,445 children and 4848 pregnant women were recruited from Tianjin, China and the relationship between the coverage rate of IS, proportion of AIS, SIC, and population iodine status was analyzed. Additionally, through the thyroid health survey project, 856 children with IS or noniodized salt were recruited. The effects of different household cooking salts on individual iodine status and thyroid health were analyzed. RESULTS: After adjusting for confounding factors, no relationship was found between the coverage rate of IS, proportion of AIS, SIC of household cooking salt, and iodine status of children and pregnant women (all P > 0.05). No differences in levels of thyroid function and structural indicators were found in children with different household cooking salts (all P > 0.05). Additionally, no relationship was found between noniodized salt exposure and goiter, overt hyperthyroidism, overt hypothyroidism, thyroid nodules, antibody single positivity, or subclinical hypothyroidism (all P > 0.05). CONCLUSION: Iodine in household cooking salt no longer plays a crucial role in iodine status in Tianjin, China. Other indicators must be identified as beneficial supplements for precise iodine status evaluation not only in Tianjin but also in other large cities in China.

Estrogen-Responsive Gene MAST4 Regulates Myeloma Bone Disease.

Our previous data showed that young female multiple myeloma (MM) patients had a low frequency of osteolytic lesions. Based on this clinical observation, we found that estrogen cell signaling played a regulatory role in MM bone disease (MMBD), and the estrogen-responsive gene microtubule-associated serine/threonine kinase family member 4 (MAST4) was a critical factor. The presence of estrogen in cell cultures promoted MAST4 expression in MM cells, while knocking down estrogen receptor 1 (ESR1) inhibited MAST4 expression. Chromatin immunoprecipitation assay suggested a binding site of ESR1 on the MAST4 promoter. Bisphosphonates, such as zoledronic acid (ZOL), which was widely used in MMBD control, could stimulate MAST4 expression in MM cells by promoting ESR1 expression. MAST4 interacted with phosphatase and tensin homolog (PTEN), therefore regulating the PI3K-Akt-mTOR pathway and the expression of downstream cytokines, such as CCL2/3/4. MAST4 knockdown (MAST4-KD) or ESR1 knockdown (ESR1-KD) MM cells had repressed PTEN activity, elevated PI3K-Akt-mTOR activity, and increased CCL2/3/4 expressions. Coculture of MAST4-KD or ESR1-KD MM cells with pre-osteoclasts (pre-OCs) stimulated OC formation in vitro, whereas neutralizing antibodies of CCL2/3/4 attenuated such stimulation. In mouse models, mice inoculated with MAST4-KD or ESR1-KD MM cells had severer MMBD than control knockdown (CTR-KD). The correlations between MAST4 and ESR1 expressions in MMBD, as well as related cell signaling pathways, were confirmed in analyses using gene expression profiles (GEPs) of patients' MM cells. The negative correlation of MAST4 expression and occurrence of MMBD was further validated by patients' immunohistochemical tissue array. Overall, our data suggested that estrogen cell signaling negatively regulated MMBD through MAST4. © 2022 American Society for Bone and Mineral Research (ASBMR).

Moderating Role of TSHR and PTPN22 Gene Polymorphisms in Effects of Excessive Fluoride on Thyroid: a School-Based Cross-Sectional Study.

We aimed to investigate the relationship between the effects excessive of fluoride on thyroid health in children and the moderating role of thyroid stimulating hormone receptor (TSHR) or protein tyrosine phosphatase nonreceptor-22 (PTPN22) gene polymorphisms. Four hundred thirteen children (141 with dental fluorosis and 198 boys) were enrolled from both historical endemic and non-endemic areas of fluorosis in Tianjin, China. The fluoride exposure levels, thyroid health indicators, and TSHR (rs2268458) and PTPN22 (rs3765598) polymorphisms were examined. Multiple logistic models were applied to evaluate the relationship between dental fluorosis and thyroid abnormalities. Children over 9 year old with dental fluorosis have lower FT4 and TGAb levels and thyroid volume and higher TPOAb levels (all P < 0.05). In overall participants, children with dental fluorosis were more likely to have thyroid antibody single positive issues (adjusted P = 0.039) and less likely to have a goiter according to age or body surface area (age or BSA) (adjusted P = 0.003); In the TSHR (rs2268458) SNP = CC/CT or PTPN22 (rs3765598) SNP = CC subgroup, dental fluorosis may cause thyroid antibody single positive (adjusted P = 0.036; adjusted P = 0.002); in the TSHR (rs2268458) SNP = TT or PTPN22 (rs3765598) SNP = CC subgroup, dental fluorosis may protect children from goiter (age or BSA) (adjusted P = 0.018; adjusted P = 0.013). Excessive fluoride may induce thyroid antibody single positive and reduce goiter in children. Heterogeneity exists in the relationship between excessive fluoride and thyroid antibody single positive or goiter issues across children carrying different TSHR (rs2268458) or PTPN22 (rs3765598) genotypes.

Long-term repetitive exposure to excess iodine induces mitochondrial apoptosis, and alters monoamine neurotransmitters in hippocampus of rats of different genders.

The influence of excess iodine on human health has been paid more and more attention. Although numerous studies have reported that excess iodine may cause deleterious effects, the mental damage and its mechanism is yet to be identified. Using Sprague-Dawley rats exposed to excess iodine from pregnancy to 6 months post-delivery as in vivo model, this study explored the impacts of long-term repetitive excess iodine administration on the hippocampus of offspring rats, focusing on mitochondrial apoptosis pathway, with changes in monoamine neurotransmitters. The results showed that excess iodine could increase urinary iodine and brain organ coefficient in offspring of both genders, change the hippocampal cell structure, and damage the spatial learning and memory capacities. Poly ADP-ribose polymerase (PARP), P53, Cleaved Caspase-3, and cytochrome C proteins expression increased and Bcl2 protein expression decreased in hippocampus of excess iodine-treated offspring, indicating that excess iodine could activate the mitochondrial apoptosis pathway. Besides, excess iodine showed different effects on monoamine neurotransmitter in different gender. Collectively, our experimental data indicated that the learning and memory impairment induced by excess iodine may be mediated via mitochondrial apoptotic pathway. Long-term repetitive excess iodine exposure affected monoamine neurotransmitters in hippocampus of offspring rats.

The cholinergic system, intelligence, and dental fluorosis in school-aged children with low-to-moderate fluoride exposure.

Disruption of cholinergic neurotransmission can affect cognition, but little is known about whether low-to-moderate fluoride exposure affects cholinergic system and its effect on the prevalence of dental fluorosis (DF) and intelligence quotient (IQ). A cross-sectional study was conducted to explore the associations of moderate fluoride exposure and cholinergic system in relation to children's DF and IQ. We recruited 709 resident children in Tianjin, China. Ion selective electrode method was used to detect fluoride concentrations in water and urine. Cholinergic system was assessed by the detection of choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and acetylcholine (ACh) levels in serum. Compared with children in the first quartile, those in fourth quartile the risk of either developing DF or IQ < 120 increased by 19% and 20% for water and urinary fluoride. The risk of having both increased by 58% and 62% in third and fourth quartile for water fluoride, 52% and 65% for urinary fluoride. Water fluoride concentrations were positively associated with AChE and negatively associated with ChAT and ACh, trends were same for urinary fluoride except for ACh. The risk of either developing DF or having non-high intelligence rose by 22% (95%CI: 1.07%, 1.38%) for the fourth quartile than those in the first quartile of AChE, for having the both, the risk was 1.27 (95%CI: 1.07, 1.50), 1.37 (95%CI: 1.17, 1.62) and 1.44 (95%CI: 1.23, 1.68) in second, third and fourth quartiles. The mediation proportion by AChE between water fluoride and either developing DF or IQ < 120 was 15.7%. For both to exist, the proportion was 6.7% and 7.2% for water and urinary fluoride. Our findings suggest low-to-moderate fluoride exposure was associated with dysfunction of cholinergic system for children. AChE may partly mediate the prevalence of DF and lower probability of having superior and above intelligence.

Minimal residual disease in multiple myeloma: current status.

Multiple myeloma (MM) is a treatable plasma cell cancer with no cure. Clinical evidence shows that the status of minimal residual disease (MRD) after treatment is an independent prognostic factor of MM. MRD indicates the depth of post-therapeutic remission. In this review article, we outlined the major clinical trials that have determined the prognostic value of MRD in MM. We also reviewed different methods that were used for MM MRD assessment. Most important, we reviewed our current understanding of MM MRD biology. MRD studies strongly indicate that MRD is not a uniform declination of whole MM tumor population. Rather, MM MRD exhibits unique signatures of cytogenetic aberration and gene expression profiles, unlike those of MM cells before therapy. Diagnostic high-risk MM and low-risk MM exhibited a diversity of MRD features. Clonal evaluation may occur at the MRD stage in MM. The dynamics from the diagnostic MM to MRD correlate with the disease prognosis. Lastly, on the aspect of omics, we performed data-based analysis to address the biological features underlying the course of diagnostic-to-MRD MM. To summarize, the MRD stage of disease represents a critical step in MM pathogenesis and progression. Demonstration of MM MRD biology should help us to deal with the curative difficulties.

Nickel-Catalyzed Hydroamination of Olefins with Anthranils.

A nickel-catalyzed polarity-reversed hydroamination of olefins has been achieved with anthranils as the electrophilic aminating agents and hydrosilane as the reductant. This protocol provides a facile access to N-alkyl-2-aminobenzophenones that are versatile intermediates in organic synthesis. A wide range of olefins and anthranils are compatible in this transformation, delivering the desired amines in useful to excellent yields (38 examples, up to 92% yield). The utility of this protocol is exhibited in the late-stage functionalization of drug molecules and the valuable derivatives of the obtained amination products.