Despite the enormous efforts to control the growth behavior of Li, achieving a dendrite‐free Li deposition and high‐energy‐density have remained an inevitable challenge of Li metal batteries. Here, ...the conformal deposition of Li metal is reported on electroactive organic materials to achieve a high‐energy‐density and electrochemical longevity. To this end, Li2C8H4O4 (Li2TP), which can act as both the electrode material (providing the redox capacity) and Li host (inducing the dendrite‐free Li deposition), is used as the model electroactive organic material. The Li2TP host exhibits reversible sequential lithiation/delithiation and Li deposition/stripping reactions. Consequently, a Li‐free full cell constructed by the Li2TP host (without pre‐charging) and a LiFePO4 cathode delivered a high areal capacity (≈3.8 mAh cm−2), exceptional rate performance (≤12 mA cm−2), and superior cyclability (80% capacity retention after 100 cycles). This electroactive organic material‐based Li host strategy can provide a new perspective for the development of practical Li metal batteries.
A conformal and dendrite‐free deposition of lithium metal on electroactive organic materials (Li2C8H4O4) is demonstrated, which can achieve both redox capacity and lithium electrodeposition stabilization. This work provides a new design concept for electroactive Li hosts that enable practical Li metal batteries with high energy density and electrochemical longevity.
Background
The sensitivity of Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL) to reduced‐intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) ...versus myeloablative conditioning (MAC) allogeneic HCT by minimal residual disease (MRD) kinetics is not well established.
Methods
This study compared long‐term outcomes based on MRD kinetics for 79 patients with RIC transplants and 116 patients with MAC transplants in first complete remission (CR1) after tyrosine kinase inhibitor–based chemotherapy (median follow‐up, 67.1 months). MRD monitoring was centrally evaluated by real‐time quantitative polymerase chain reaction for all patients.
Results
RIC showed a cumulative incidence of relapse (CIR; 30.6% vs 31.7%), nonrelapse mortality (17.5% vs 14.9%), disease‐free survival (DFS; 51.9% vs 53.4%), and overall survival (61.1% vs 61.4%) comparable to those associated with MAC. In all MRD kinetics–based subgroups, no differences in CIR (early complete molecular response CMR, 19.3% vs 4.8%; early major molecular response MMR, 17.0% vs 26.8%; late CMR, 20.0% vs 14.3%; late MMR, 28.3% vs 31.0%; poor molecular response PMR, 57.9% vs 62.4%) or DFS (early CMR, 71.6% vs 76.2%; early MMR, 66.9% vs 52.1%; late CMR, 50.0% vs 64.3%; late MMR, 50.7% vs 53.7%; PMR, 31.6% vs 34.1%) were observed between RIC and MAC. In a multivariate analysis, the conditioning intensity had no significant impact on transplantation outcomes.
Conclusions
RIC is a valid alternative choice for long‐term disease control and is worthy of further investigation in prospective trials for adult Ph‐positive ALL in CR1.
Reduced‐intensity conditioning shows long‐term outcomes comparable to those with myeloablative conditioning in adults with Philadelphia chromosome–positive acute lymphoblastic leukemia who undergo hematopoietic cell transplantation during their first complete remission after tyrosine kinase inhibitor–based chemotherapy. The sensitivity of Philadelphia chromosome–positive acute lymphoblastic leukemia to reduced‐intensity conditioning versus myeloablative conditioning is not different in all minimal residual disease kinetics–based patient subgroups.
Background
In this post hoc analysis of the PRODIGY study, we aimed to investigate factors associated with survival outcomes and provide evidence for designing optimal perioperative treatment ...strategies for gastric cancer patients receiving neoadjuvant chemotherapy.
Patients and methods
A total of 212 patients in the neoadjuvant chemotherapy group of the PRODIGY study were included as the study population. The prognostic impact of clinicopathologic factors, including the initial radiological clinical stage (cStage) and post-neoadjuvant chemotherapy pathological stage (ypStage), was analyzed.
Results
The median age was 58 years. The majority of patients (77.4%) had cStage III disease, and about 10% and 25% had ypStage 0 and I disease, respectively. According to the initial cStage, progression-free survival (PFS) and overall survival (OS) were significantly different (
P
< 0.01). PFS and OS were also different according to the ypStage (
P
< 0.01). In multivariate analyses, cStage IIIC disease (vs. cStage II) and ypStage II and III disease (vs. ypStage 0/I) were independent factors for poor survival outcomes. Based on the patterns of PFS and OS according to both cStage and ypStage, three patient groups were defined. These groups showed distinct PFS and OS (
P
< 0.01) with 5-year PFS rates of 95.7%, 77.9%, and 31.3% and 5-year OS rates of 95.7%, 82.4%, and 42.5%, respectively.
Conclusions
Both initial cStage and ypStage were independent factors for survival outcomes of gastric cancer patients treated with neoadjuvant chemotherapy. Efforts should be made to develop optimal peri-operative treatment strategies for patients at different risks according to cStage and ypStage.
In acute promyelocytic leukemia (APL), increased cell burden in the peripheral blood due to either the disease itself or early treatment with all-trans retinoic acid could cause hyperleukocytosis ...(HL) before induction chemotherapy. However, therapeutic leukapheresis has seldom been used because of concerns of subsequent coagulopathy after this invasive procedure. The aim of this study was to evaluate the effects of leukapheresis in APL, especially for efficacy and safety.
We retrospectively analyzed newly diagnosed patients with APL from January 2009 to March 2022. Among 323 patients, 85 had white blood cell count above 40 × 109/L before induction chemotherapy. Thirty-nine patients were initially treated with leukapheresis, whereas the other 46 were not. Clinical and laboratory parameters between these groups were compared.
There was a trend toward favorable 30-day survival rate for the leukapheresis group compared with the non-leukapheresis group (76.9% and 67.4%; P = 0.24). The complications including subsequent intensive unit care (P = 0.23), severe hemorrhagic events (P = 0.13) showed no significant differences between the two groups. The patients were divided into subcohorts, and the survival rates of the leukapheresis and non-leukapheresis groups were 92.3% (95% confidence interval CI, 77.8%–100.0%) versus 58.3% (95% CI, 38.6%–78.1%) (P = 0.03) in “sequential HL” and 76.7% (95% CI, 61.5%–91.8%) versus 54.8% (95% CI, 37.3%–72.4%) (P = 0.03) in “symptomatic HL,” respectively. Moreover, in the “sequential HL” subcohort, the cumulative incidence of differentiation syndrome and following adverse events were significantly lower in the leukapheresis group.
In APL with “sequential HL” or “symptomatic HL” from either the disease itself or the effect of all-trans retinoic acid, therapeutic leukapheresis could be applied to reduce leukemic cell burden without significant risks.
Video-assisted thoracoscopic surgery (VATS) is widely performed in patients with resectable non-small cell lung cancer. However, it is unknown whether VATS sublobar resection has advantages compared ...with VATS lobectomy in preserving pulmonary function.
Three hundred patients with non-small cell lung cancer who underwent VATS were enrolled. Pulmonary function tests were performed three times: preoperatively, and at 3 and 12 months postoperatively. Pulmonary function was compared between the VATS lobectomy group (n = 227) and the VATS sublobar resection group (n = 73).
The VATS sublobar resection group had greater preserved pulmonary function than the VATS lobectomy group at 3 and 12 months postoperatively (p < 0.001). However, a VATS lobectomy of the right upper or right middle lobe revealed no difference in forced vital capacity (-1.21% versus -1.45%; p = 0.88) or the diffusion capacity of carbon monoxide (-3.99% versus -2.45%; p = 0.61) compared with VATS sublobar resection after 12 months. In those who underwent VATS of the right lower lobe, forced expiratory volume in 1 second (-8.60% versus -3.69%; p = 0.12) was not different between the two groups after 12 months. Video-assisted thoracoscopic surgery lobectomy of the left upper or left lower lobe resulted in lower pulmonary function than VATS sublobar resection (p < 0.05).
Patients with non-small cell lung cancer who underwent VATS sublobar resection demonstrated greater pulmonary function than those who underwent VATS lobectomy. However, in right-side VATS lobectomy, some differences dissipated at 1 year.
Display omitted
•Bimetallic cobalt–bismuth oxide (CBO) was prepared by a simple hydrothermal method.•Nanoneedles morphology of CBO with an average diameter of 10 nm was achieved.•The Li+ insertion ...mechanism was two-stage conversion–alloying reactions.•The stepwise Li+-uptake effectively suppressed the volume expansion upon cycling.•CBO offered long-term stability with 0.05 mAh g−1 loss per cycle over 1000 cycles.
Materials that undergo combined conversion and alloying reactions are promising as anodes for lithium storage application because they can accommodate multiple lithium ions. However, irreversible conversion reactions, large voltage hysteresis, poor rate capabilities, and low initial Coulombic efficiencies during continuous discharge–charge cycling make practical applications of conversion–alloying materials challenging. Herein, we present cobalt–bismuth oxide (CBO) nanoneedles, a new bimetallic material in which Li+-ion uptake proceeds stepwise, thus effectively suppressing volume expansion. During the initial lithiation stage, the CBO nanoneedles undergo a conversion reaction to form nanodomains of low-oxidation-state Coδ+ (δ ≤ 2) in a Li2O matrix. At the next potential platform, the Bi phase attracts Li+ ions via an alloying reaction, while the Coδ+/Li2O phase hinders excessive volume expansion. Consequently, the CBO electrode delivers a high reversible discharge capacity of 392 mAh g−1 at 50 mA g−1 for up to 100 cycles. Further, an ultrastable long-term capacity of 300 mAh g−1 at 250 mA g−1 is realized over 1000 cycles. The stepwise lithiation process decreases volume expansion significantly (by ∼10%), which leads to good cyclability. Owing to their ease of preparation and excellent performance characteristics, CBO nanoneedles are an attractive long-life anode material for lithium-ion batteries.
The risk of lung cancer is higher in idiopathic pulmonary fibrosis (IPF) because both conditions share common risk factors. However, no standard treatment modality for LC in IPF exists due to rare ...incidence, poor prognosis, and acute exacerbation (AE) of IPF during treatment. We aimed to determine the efficacy of LC treatments and the prognosis in LC patients with IPF according to the LC stage and GAP (gender G, age A, and two physiology variables P) stage. From 2003 to 2016, 160 retrospectively enrolled patients were classified according to the LC clinical stage and GAP stage. The average (±standard deviation) patient age was 70.1 ± 8.2 years; the cohort predominantly comprised men (94.4%). In GAP stage I, surgery was significantly associated with better survival outcomes in LC. In contrast, no treatment modality yielded significant clinical improvement in GAP stage II/III. The incidences of AE in IPF and its mortality during treatment were 13.8% and 6.3%, respectively. AE occurred commonly in advanced GAP stage. Active treatment should be considered in GAP stage I. The performance status and LC stage should be considered when deciding about the necessity of surgery for patients in advanced GAP stage.
Markers of the epithelial-to-mesenchymal transition (EMT) in gastric tumor tissues are associated with poor patient outcomes. We performed a screen to identify pharmacologic compounds that kill ...gastric cancer cells with EMT-associated gene expression patterns and investigate their mechanisms.
We identified 29 gastric cancer cell lines with a gene expression signature previously associated with an EMT subtype, based on data from RNA sequence analyses, and confirmed the mesenchymal phenotypes of 7 lines (Hs746T, SNU1750, MKN1, SK4, SNU484, SNU668, and YCC11), based on invasive activity and protein markers. We screened 1,345 compounds for their ability to kill cells with the EMT signature compared with cell lines without this pattern. We tested the effects of identified compounds in BALB/c nude mice bearing GA077 tumors; mice were given intraperitoneal injections of the compound or vehicle (control) twice daily for 24 days and tumor growth was monitored. Proteins associated with the toxicity of the compounds were overexpressed in MKN1 and SNU484 cells or knocked down in MKN45 and SNU719 using small interfering RNAs. We performed immunohistochemical analyses of 942 gastric cancer tissues and investigated associations between EMT markers and protein expression patterns.
The nicotinamide phosphoribosyltransferase inhibitor FK866 killed 6 of 7 gastric cancer cell lines with EMT-associated gene expression signatures but not gastric cancer cells without this signature. The 6 EMT-subtype gastric cell lines expressed significantly low levels of nicotinic acid phosphoribosyltransferase (NAPRT), which makes the cells hypersensitive to nicotinamide phosphoribosyltransferase inhibition. Gastric cell lines that expressed higher levels of NAPRT, regardless of EMT markers, were sensitized to FK866 after knockdown of NAPRT, whereas overexpression of NAPRT in deficient EMT cell lines protected them from FK866-mediated toxicity. Administration of FK866 to nude mice with tumors grown from GA077 cells (human gastric cancer tumors of the EMT subtype) led to tumor regression in 2 weeks; FK866 did not affect tumors grown from MKN45 cells without the EMT expression signature. Loss of NAPRT might promote the EMT, because it stabilizes β-catenin. We correlated the EMT gene expression signature with lower levels of NAPRT in 942 gastric tumors from patients; we also found lower levels of NAPRT mRNA in colorectal, pancreatic, and lung adenocarcinoma tissues with the EMT gene expression signature.
FK866 selectively kills gastric cancer cells with an EMT gene expression signature by inhibiting nicotinamide phosphoribosyltransferase in cells with NAPRT deficiency. Loss of NAPRT expression, frequently through promoter hypermethylation, is observed in many gastric tumors of the EMT subtype. FK866 might be used to treat patients with tumors of this subtype.
Display omitted
Abstract
Along with early-onset cancers, multiple primary cancers (MPCs) are likely resulting from increased genetic susceptibility; however, the associated predisposition genes or prevalence of the ...pathogenic variants genes in MPC patients are often unknown. We screened 71 patients with MPC of the stomach, colorectal, and endometrium, sequencing 65 cancer predisposition genes. A subset of 19 patients with early-onset MPC of stomach and colorectum were further evaluated for variants in cancer related genes using both normal and tumor whole exome sequencing. Among 71 patients with MPCs, variants classified to be pathogenic were observed in 15 (21.1%) patients and affected Lynch Syndrome (LS) genes:
MLH1
(n = 10),
MSH6
(n = 2),
PMS2
(n = 2), and
MSH2
(n = 1). All carriers had tumors with high microsatellite instability and 13 of them (86.7%) were early-onset, consistent with LS. In 19 patients with early-onset MPCs, loss of function (LoF) variants in
RECQL5
were more prevalent in non-LS MPC than in matched sporadic cancer patients (OR = 31.6, 2.73–1700.6,
p
= 0.001). Additionally, there were high-confidence LoF variants at
FANCG
and
CASP8
in two patients accompanied by somatic loss of heterozygosity in tumor, respectively. The results suggest that genetic screening should be considered for synchronous cancers and metachronous MPCs of the LS tumor spectrum, particularly in early-onset. Susceptibility variants in non-LS genes for MPC patients may exist, but evidence for their role is more elusive than for LS patients.
Scleroderma is an autoimmune disease caused by the abnormal regulation of extracellular matrix synthesis and is activated by non-regulated inflammatory cells and cytokines. Echinochrome A (EchA), a ...natural pigment isolated from sea urchins, has been demonstrated to have antioxidant activities and beneficial effects in various disease models. The present study demonstrates for the first time that EchA treatment alleviates bleomycin-induced scleroderma by normalizing dermal thickness and suppressing collagen deposition in vivo. EchA treatment reduces the number of activated myofibroblasts expressing α-SMA, vimentin, and phosphorylated Smad3 in bleomycin-induced scleroderma. In addition, it decreased the number of macrophages, including M1 and M2 types in the affected skin, suggesting the induction of an anti-inflammatory effect. Furthermore, EchA treatment markedly attenuated serum levels of inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ, in a murine scleroderma model. Taken together, these results suggest that EchA is highly useful for the treatment of scleroderma, exerting anti-fibrosis and anti-inflammatory effects.
PDF
