Solid-State, Hectogram-Scale Preparation of Red Carbon Dots as Phosphor for Energy-Transfer-Induced High-Quality White LEDs with CRI of 97.

In this study, pre-crystallization-controlled, solid-state preparation of red carbon dots (C-dots) from o-phenylenediamine on a hectogram scale with a 94% yield is reported. Highly efficient red phosphor (C-dots@MCC) is obtained by dispersing the C-dots in microcrystalline cellulose, which matched extremely well with the commercial Y3 Al5 O12 :Ce3+ (YAG) phosphor. White light-emitting diodes (WLEDs) fabricated from the two phosphors emitted warm white light with a correlated color temperature of 3845 K, CIE color coordinates of (0.38, 0.37), and an extremely high color rendering index (CRI) of 95, outperforming all the reported YAG-derived WLEDs. Furthermore, the CRI value of the WLED can be further increased to 97 after fine-tuning, which is the highest CRI for WLEDs of any C-dots derived devices reported so far. The superior performance of the WLED is attributed to a delicate energy transfer between YAG and C-dots@MCC. Most importantly, the WLED maintained excellent stabilities under varied currents, working durations, moistures, and temperatures.

Carbon Dots-Based Fluorescence Assay for the Facile and Reliable Detection of Ag+ in Natural Water and Serum Samples.

In this report, red-emissive carbon dots (C-dots) were facilely prepared from o-phenylenediamine via microwave-assisted hydrothermal treatment. The C-dots demonstrated excitation wavelength-independent emission with maximums at 621 nm that could be effectively quenched by Ag+ via static quenching. This phenomenon was exploited to establish a sensitive fluorescence assay with a low detection limit (0.37 µM) and wide linear range (0-50 µM). In addition, this assay demonstrated excellent selectivity toward Ag+, free from the interference of 16 commonly seen metal ions. Most importantly, the assay demonstrated high reliability toward samples in deionized water, mineral water, lake water, and serum, which could indicate potential applications for Ag+ monitoring in complicated natural and biological environments.

Distinct mutational features across preinvasive and invasive subtypes identified through comprehensive profiling of surgically resected lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a heterogeneous disease. Our study aimed to understand the unique molecular features of preinvasive to invasive LUAD subtypes. We retrospectively analyzed the clinical, histopathological, and molecular data of 3,254 Chinese patients with preinvasive lesions (n = 252), minimally invasive adenocarcinomas (n = 479), and invasive LUAD (n = 2,523). Molecular data were elucidated using a targeted 68-gene next-generation sequencing panel. Our findings revealed four preinvasive lesion-predominant gene mutations, including MAP2K1 insertion-deletions (indels), BRAF non-V600E kinase mutations, and exon 20 insertions (20ins) in both EGFR and ERBB2, which we referred to as mutations enriched in AIS (MEA). The detection rate of MEA in invasive tumors was relatively lower. MAP2K1 missense mutations, which were likely passenger mutations, co-occurred with oncogenic driver mutations, while small indels were mutually exclusive from other genes regardless of the invasion level. BRAF non-V600E kinase-mutant invasive adenocarcinomas (IAC) had significantly higher mutation rates in tumor suppressor genes but lower frequency of co-occurring oncogenic driver mutations than non-kinase-mutant IAC, suggesting the potential oncogenic activity of BRAF non-V600E kinase mutations albeit weaker than BRAF V600E. Moreover, similar to the extremely low frequency of MAP2K1 indels in IAC, BRAF non-V600E kinase domain mutations co-occurring with TSC1 mutations were exclusively found in preinvasive lesions. Compared with EGFR L858R and exon 19 deletion, patients with preinvasive lesions harboring 20ins in either EGFR or ERBB2 were significantly younger, while those with IAC had similar age. Furthermore, our study demonstrated distinct mutational features for subtypes of oncogene mutations favored by different invasion patterns in adenocarcinomas. In conclusion, our data demonstrate distinct mutational features between preinvasive lesions and invasive tumors with MEA, suggesting the involvement of MEA in the early stages of tumorigenesis. Further pre-clinical studies are required to establish the role of these genes in the malignant transformation of LUAD.

Synthesis Mechanisms, Structural Models, and Photothermal Therapy Applications of Top-Down Carbon Dots from Carbon Powder, Graphite, Graphene, and Carbon Nanotubes.

In this study, top-down syntheses of carbon dots (CDs) from four different carbon precursors, namely, carbon nano powders, graphite, graphene, and carbon nanotubes, were carried out. Systematic study demonstrated that the optical properties and surface functionalities of the CDs were quite similar and mainly influenced by the synthesis method, while the sizes, morphologies, chemical compositions, and core structures of the CDs were heavily influenced by the carbon precursors. On the basis of these studies, the formation processes and structural models of these four top-down CDs were proposed. The cell cytotoxicity and photothermal conversion efficiency of these CDs were also carefully evaluated, demonstrating their potential applications in photothermal therapy.

Single nucleotide polymorphism at alcohol dehydrogenase-1B is associated with risk of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous incidence in many developed countries has increased dramatically over last decades, while the underlying mechanism of the biogenesis of ES was still unknown. METHODS: Here, we investigate 1001 subjects with esophageal cancer recruited from the affiliated hospital of Shanghai Jiao Tong University from Jan. 1, 2001 to Feb. 2, 2004. Single nucleotide polymorphism (SNP) of alcohol dehydrogenase-1B (ADH1B) was performed, and the recombinant plasimd containing ADH1B was constructed. Then, the ADH1B was purified and the enzymatic activity was assayed according to the methodology of Quayle. Furthermore, the effect of ADH1B on proliferation of human esophageal squamous cell lines was determined and the underlying mechanism of ADH1B was investigated. RESULTS: Logistic regression analyses revealed that subjects carrying the GG variant homozygote had a significant 2.81-fold (adjusted OR = 2.81; 95% CI = 2.18-3.62) increased risk of esophageal cancer. We found that SNP of ADH1B (GG) significantly promotes cell proliferation in ESGG. ADH1B (GG) could down-regulate endogenous ADH1B expression at posttranscriptional level. Moreover, re-expression of ADH1B in cells transfected with ADH1B (AA) significantly inhibits cell proliferation. CONCLUSIONS: Our data implied that ADH1B (GG) could promote cell proliferation in human ESGG through regulating the enzyme activity of ADH1B. Therefore, we propose that ADH1B might be used as a therapeutic agent for human ESGG.

Surgical treatment of early-stage thymomas: robot-assisted thoracoscopic surgery versus transsternal thymectomy.

BACKGROUND: This study aimed to compare the perioperative outcomes for patients who underwent transsternal or robot-assisted thymectomy and to determine the feasibility of robot-assisted thymectomy for the treatment of Masaoka stages 1 and 2 thymomas. METHODS: The study evaluated the short-term outcomes for 74 patients undergoing surgery for Masaoka stages 1 and 2 thymomas without myasthenia gravis between January 2009 and December 2012. Of these 74 patients, 23 underwent thymoma resection using unilateral robot-assisted thoracoscopic surgery (RATS group), and 51 underwent transsternal thymectomy (TST group). Duration of surgery, amount of intraoperative blood loss, duration of chest drainage, duration of postoperative hospital stay, and postoperative complications were evaluated. RESULTS: The intraoperative blood loss was significantly less in the RATS groups (61.3 ml) than in the TST group (466.1 ml) (p < 0.01). The postoperative hospital stay was significantly shorter in the RATS group (3.7 vs 11.6 days; p < 0.01). No patients in the RATS group underwent conversion to open surgery. No severe surgical complications (e.g., bleeding caused by injury to the left brachiocephalic vein) and only one case of pulmonary atelectasis (appearing in a male patient 2 days after surgery) were detected in this series. CONCLUSION: Robot-assisted thoracoscopic thymectomy for early-stage thymomas is technically feasible, safe, and less invasive for the patient.

Modified coconut shell biochars (MCSBCs): Fabrication and their adsorptions for Pb(II).

The modified coconut shell biochars (MCSBCs) were fabricated and their adsorptions for Pb(II) were evaluated, in which waste coconut shell was used as the raw material, both ZnCl2 and KMnO4 were applied as the inorganic modifiers. FT-IR spectra, TGA, SEM and BET techniques were utilized to characterize their properties. It was spotted that the thermal stability of UCSBC could arrive at 500 °C. The BET specific surface areas of both Zn- and Mn-modified MCSBCs (485.137, 476.734 m2/g) were highly decreased as compared with that of UCSBC (3528.78 m2/g). In contrast, the average pore diameters of both Zn- and Mn-modified MCSBCs (3.295, 3.803 nm) were smaller than that of UCSBC (3.814 nm). These findings reveal that the modification of CSBC didn't change its pore size. Their adsorptions for Pb(II) were performed and some controlling factors involving pH, contact time, starting concentration and temperature were explored. Moreover, the experiment data were fitted via linear and non-linear techniques. It was found that the Langmuir maximal adsorption amounts of un-modified coconut shell biochar (UCSBC), Zn-modified and Mn-modified MCSBCs for Pb(II) could reach 31.653, 86.547 and 93.666 mg/g, respectively. Two-parameter kinetic models exposed that Pb(II) adsorption on UCSBC, Zn-modified and Mn-modified MCSBCs obeyed both the Lagergren first-order (non-linear R2 = 0.990, 0.954, 0.953, respectively) and Avrami fractional-order (non-linear R2 = 0.989, 0.946, 0.945, respectively) kinetic models. Two-parameter and three-parameter isotherm models verified that Pb(II) adsorption on UCSBC, Zn-modified and Mn-modified MCSBCs followed the Langmuir (non-linear R2 = 0.992, 0.997, 0.993, respectively) as well as Sips (non-linear R2 = 0.992, 0.997, 0.992, respectively) isotherm models. The computation of thermodynamic parameters evidenced that the modification of UCSBC via KMnO4 and ZnCl2 can effectively rise its adsorption for Pb(II), exhibiting promising applications in the handling of metal-bearing water.

Synthesis of ultrathin hybrid membranes via the co-polymerization of acrylic acid, styrene and molybdenum disulfide and their high adsorption selectivity for lead(II) in the mixture of metal ions.

Lead(II) is a potential carcinogen of heavy-metal ions (HIs). With the wide application of Pb-bearing products including lead alloy products, and new-energy lead-ion batteries, lead pollution has become a tricky problem. To solve such a difficulty, novel ultrathin MoS2-vinyl hybrid membranes (MVHMs) with a "spring" effect were synthesized via co-polymerization of acrylic acid, styrene and molybdenum disulfide (MoS2) and their adsorptions for HIs were explored. The "spring" effect derived from the interaction between the tendency of the short polyacrylic acid (PAA) chain connected with MoS2 to spread outward and the coulomb force between layers from MoS2 (s-MoS2), which enlarge the spacing of MoS2 layers without changing the number of layers after membrane formation, which changes the swelling membrane to a dense membrane and reduces the original thickness from 0.5 cm to 0.011 mm in the thickness direction. The adsorption experiment revealed that these MVHMs had super adsorption performance and high selectivity for Pb2+ by comparison with other five metal ions: Cu2+, Cd2+, Ni2+, Cr3+ and Zn2+. Especially, the adsorption quantity of MVHMs for Pb2+ could approach 2468 mg/g and the maximum adsorption ratio of qe[Pb2+]/qe[Cu2+] can reach 10.909. These values were much larger than the data obtained with the adsorbents reported in the last decade. A variety of models are applied to evaluate the effect of ionic groups. It was confirmed that -COOH plays a key role in adsorption of HIs and s-MoS2 also has a certain contribution. Conversely, ion exchange plays only a minor role during the period of adsorption process. Effective diffusion coefficient (Deff) of Pb(II) had the largest values among these metal ions. Hence, these hybrid membranes are promising adsorbents for the removal of Pb2+ from water containing various ions.

A Multicenter Retrospective Case-Control Study on Simple vs Extended Sleeve Lobectomies.

BACKGROUND: Sleeve resection is currently the gold standard procedure for centrally located non-small cell lung cancer (NSCLC). Extended sleeve lobectomy (ESL) consists of an atypical bronchoplasty with resection of >1 lobe and carries several technical difficulties compared with simple sleeve lobectomy (SSL). Our study compared the outcomes of ESL and SSL for NSCLC. METHODS: This multicenter, retrospective, cohort study included 1314 patients who underwent ESL (155 patients) or SSL (1159 patients) between 2000 and 2018. The primary end points were 30-day and 90-day mortality, overall survival (OS), disease-free survival (DFS), and complications. RESULTS: No differences were found between the 2 groups in general characteristics and surgical and survival outcomes. In particular, there were no differences in early and late complication frequency, 30- and 90-day mortality, R status, recurrence, OS (54.26 ± 33.72 months vs 56.42 ± 32.85 months, P = .444), and DFS (46.05 ± 36.14 months vs 47.20 ± 35.78 months, P = .710). Mean tumor size was larger in the ESL group (4.72 ± 2.30 cm vs 3.81 ± 1.78 cm, P < .001). Stage IIIA was the most prevalent stage in ESL group (34.8%), whereas stage IIB was the most prevalent in SSL group (34.3%; P < .001). The multivariate analyses found nodal status was the only independent predictive factor for OS. CONCLUSIONS: ESL gives comparable short- and long-term outcomes to SSL. Appropriate preoperative staging and exclusion of metastases to mediastinal lymph nodes, as well as complete (R0) resection, are essential for good long-term outcomes.

Molecular, clinicopathological characteristics and surgical results of resectable SMARCA4-deficient thoracic tumors.

PURPOSE: SMARCA4-deficient thoracic tumors are rapid aggressive malignancies, often diagnosed at an advanced and inoperable stage. The value of pulmonary resection for resectable SMARCA4-deficient thoracic tumors is largely unknown. METHODS: In this observational study, we included 45 patients who received surgery for stage I-III SMARCA4-deficient tumors. We compared the molecular, clinicopathological characteristics and survival between SMARCA4-dNSCLC and SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) patients. RESULTS: Thirty-four SMARCA4-dNSCLC and 11 SMARCA4-dUT patients were included in this study. Molecular profiles were available in 33 out of 45 patients. The most common mutated gene was TP53 (21, 64%), and followed by STK11 (9, 27%), KRAS (5, 15%), FGFR1 (4, 12%) and ROS1 (4, 12%). There were 3 patients that harbored ALK mutation including 1 EML4-ALK rearrangement. There were 2 patients that harbored EGFR rare site missense mutation. SMARCA4-dUT patients had significance worse TTP (HR = 4.35 95% CI 1.77-10.71, p = 0.001) and OS (HR = 4.27, 95% CI 1.12-16.35, p = 0.022) compared to SMARCA4-dNSCLC patients. SMARCA4-dUT histologic type, stage II/III, R1/2 resection and lymphovascular invasion were independent poor prognostic predictors for both TTP and OS. There were 8 patients who received immunotherapy, the objective response rate was 50%. The SMARCA4-dNSCLC patient with ALK rearrangement was treated with crizotinib as second-line therapy, and achieved stable disease for 9.7 months. CONCLUSION: Patients with SMARCA4-deficient tumors have a high probability of early recurrence after surgery, except for stage I patients. Immunotherapy seems to be a valuable strategy to treat recurrence.

Minimally invasive sleeve lobectomy for centrally located lung cancer: A real-world study with propensity-score matching.

Background: The safety, feasibility, and prognosis of sleeve lobectomy by minimally invasive surgery (MIS) remain to be validated. The purpose of this study was to investigate outcomes in real-world patients receiving minimally invasive sleeve lobectomy in a balanced large cohort. Methods: Between January 2013 and December 2018, 578 consecutive patients undergoing sleeve resection at a high-volume center were retrospectively analyzed. Surgical and oncologic outcomes were compared between MIS and thoracotomy patients after propensity-score matching (PSM). Results: MIS sleeve lobectomy was increasingly used as a time-trend in real-world. Before PSM, the MIS group had smaller tumor size, more T2-stage cases, and more right upper lobe sleeve lobectomies compared to the Open group. After 1:4 PSM by patient demographics and tumoral characteristics, 100 cases of MIS and 338 cases of Open sleeve lobectomy were further analyzed. Although median operation time was longer in the MIS group than in the Open group (170.5 minutes vs.149.5 minutes, P < 0.001), patients in MIS group had significantly less estimated intraoperative blood loss (100 ml vs. 200 ml, P = 0.003), shorter drainage duration (5 days vs. 6 days, P = 0.027) and less amount of drainage (1280 ml vs. 1640 ml, P < 0.001) after surgery. Complete resection rate, combined angioplasty, number of dissected lymph nodes, post-operative length of stay, postoperative morbidity and mortality rate, and application of adjuvant therapy were similar between the two matched groups. Conversion to open thoracotomy was necessary in 13.6% patients, but with similar perioperative outcomes compared to Open cases except for longer operation time. More lower lobe sleeve lobectomies were accomplished via robot-assisted thoracoscopic surgery than via video-assisted thoracoscopic surgery (40.0% vs. 12.0%, P = 0.017) in MIS patients. Five-year overall survivals (MIS vs. Open: 72.7% vs. 64.4%, P = 0.156) and five-year progression-free survivals (MIS vs. Open: 49.2% vs. 50.5%, P = 0.605) were similar between the two matched groups. Conclusions: MIS sleeve lobectomy is associated with similar or even better perioperative results and oncologic outcomes to open thoracotomy. Conversion to thoracotomy does not compromise perioperative outcomes. Robot surgery may be preferable for more complex sleeve resections.

Osimertinib as neoadjuvant therapy in patients with EGFR-mutant resectable stage II-IIIB lung adenocarcinoma (NEOS): A multicenter, single-arm, open-label phase 2b trial.

OBJECTIVES: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been approved for EGFR-mutant non-small-cell lung cancer (NSCLC). We aimed to evaluate the efficacy and safety of neoadjuvant osimertinib in patients with EGFR-mutant resectable locally advanced NSCLC. MATERIALS AND METHODS: This single-arm, phase 2b trial (ChiCTR1800016948) was conducted at six centers in mainland China. Patients with a measurable stage IIA-IIIB (T3-4 N2) lung adenocarcinoma and EGFR exon 19 and/or 21 mutations were enrolled. The patients were treated with osimertinib 80 mg orally once per day for six weeks, followed by surgical resection. The primary endpoint was the objective response rate (ORR) assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1. RESULTS: Between October 17, 2018, and June 08, 2021, 88 patients were screened for eligibility. Forty patients were enrolled and treated with neoadjuvant osimertinib therapy. The ORR was 71.1 % (27/38) (95 % confidence interval: 55.2-83.0) in 38 patients who completed the 6-week osimertinib treatment. Thirty-two patients underwent surgery, and 30 (93.8 %) underwent successful R0 resection. Thirty (75.0 %) of 40 patients had treatment-related adverse events during neoadjuvant treatment, and three (7.5 %) had treatment-related adverse events of grade 3. The most common treatment-related adverse events were rash (n = 20 [50 %]), diarrhea (n = 12 [30 %]), and oral ulceration (n = 12 [30 %]). CONCLUSIONS: The third-generation EGFR TKI osimertinib, with satisfying efficacy and acceptable safety profile, could be a promising neoadjuvant therapy in patients with resectable EGFR-mutant NSCLC.

TRIM46 activates AKT/HK2 signaling by modifying PHLPP2 ubiquitylation to promote glycolysis and chemoresistance of lung cancer cells.

The incidence of lung cancer is increasing worldwide. Although great progress in lung cancer treatment has been made, the clinical outcome is still unsatisfactory. Tripartite motif (TRIM)-containing proteins has been shown to be closely related to tumor progression. However, the function of TRIM46 in lung cancer is largely unknown. Here, TRIM46 amplification was found in lung adenocarcinoma (LUAD) tissues and TRIM46 amplification was significantly associated with a poor survival rate. Overexpression of wild type TRIM46 increased the proliferation of LUAD cells and glycolysis, promoted xenografts growth, and enhanced cisplatin (DDP) resistance of LUAD cells via increased ubiquitination of pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) and upregulation of p-AKT. In contrast, overexpression of RING-mutant TRIM46 did not show any effects, suggesting the function of TRIM46 was dependent on the E3 ligase activity. Furthermore, we found that TRIM46 promoted LUAD cell proliferation and DDP resistance by enhancing glycolysis. PHLPP2 overexpression reversed the effects of TRIM46 overexpression. Amplification of TRIM46 also promoted LUAD growth and enhanced its DDP resistance in a patient-derived xenograft (PDX) model. In conclusion, our data highlight the importance of TRIM46/PHLPP2/AKT signaling in lung cancer and provide new insights into therapeutic strategies for lung cancer.

Management of incidentally detected small anterior mediastinal nodules: Which way to go?

OBJECTIVES: With increasing use of CT screening for lung cancers, there is a tendency toward increased detection of asymptomatic small anterior mediastinal nodules (SAMNs). In face of high rate of non-therapeutic surgery in these patients, workup and follow-up strategy for such lesions remains to be established. MATERIALS AND METHODS: This is a real-world study in patients with SAMNs (baseline diameter ≤ 3 cm) during 2013-2018. Interval growth of the nodules was reviewed. Accuracy of preoperative diagnosis was evaluated, and tumor doubling time (TDT) was calculated in resected tumors. RESULTS: A total of 419 patients were entered into the study, among them 91 received surgery. Eighty-four patients (92.3%) turned out to have thymic tumors, with a non-therapeutic surgery rate of only 6.6%. For 73 patients receiving both CT and MRI examinations, the sensitivity for diagnosing thymic tumors by CT alone was merely 72.1%, which was significantly improved to 97.1% (p < 0.001) when MRI was incorporated. Among 38 thymic tumor patients who had previous CT scan before surgery, significant difference in median TDT was seen between low-grade tumors and intermediate-/high-grade tumors (23.8 vs. 10.1 months, p = 0.021). Of the 328 patients not receiving surgery, 269 (82.0%) were diagnosed of having benign cysts by CT + MRI, followed by 24 (7.3%) lymph nodes, 22 (6.7%) thymic hyperplasia, and 13 (4%) thymic tumors. During follow-up (median 33 months), 319 (97.3%) lesions remained unchanged. CONCLUSION: The majority of incidentally detected SAMNs remain stable during long-term follow-up. Incorporating MRI with CT scan is helpful in differentiating benign cysts from small thymic tumors, thus avoiding non-therapeutic intervention. Follow-up is safe and warranted upon first detection when high-grade malignancies could be ruled out by careful imaging studies.

Anti-inflammation and adhesion enhancement properties of the multifunctional LPxTG-motif surface protein derived from the Lactobacillus reuteri DSM 8533.

LPxTG-motif protein (LMP) is one kind of a precursor protein that contains a conserved LPxTG-motif at the C-terminus, which can be recognized by sortase A (SrtA) and covalently bind to the bacterial peptidoglycan. In this study, LMP derived from Lactobacillus reuteri (L. reuteri) was heterologous expressed and the tolerance and intestinal colonization ability of the LMP on L. reuteri were analyzed in simulated gastrointestinal fluid. Meanwhile, the anti-inflammatory activity of LMP was also evaluated in the LPS-stimulated RAW 264.7 cell model. The results indicated that LMP can promote the intestinal survival rate and adhesion characteristics of L. reuteri and enhanced the autoinducer-2 (AI-2) signaling molecule of the Lactobacillus strains in quorum sensing. Furthermore, LMP can inhibit the expressions of inflammatory cytokine TNF-α and IL-1ß via ERK-JNK related MAPK signaling cascades. These findings provide a better understanding of the multifunctional LPxTG-motif surface protein derived from L. reuteri in the gastrointestinal tract environment.

Low expression of INMT is associated with poor prognosis but favorable immunotherapy response in lung adenocarcinoma.

Background: The expression of INMT (indolethylamine N-methyltransferase) has been reported to be downregulated in non-small-cell lung cancer (NSCLC). However, the role of INMT in NSCLC remains elusive. We aim to investigate the underlying mechanisms and clinical value of INMT in NSCLC, especially in lung adenocarcinoma (LUAD). Methods: Gene expression cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to assess the effect of INMT on NSCLC. Gene expression data from an immunotherapy cohort were used to investigate the association of INMT with immunotherapy in NSCLC. Results: INMT expression was significantly downregulated in NSCLC compared with adjacent normal tissues. Downregulated INMT was associated with poor overall survival in LUAD, but not in lung squamous carcinoma. Multivariate Cox regression analysis suggested that INMT was an independent prognostic marker in LUAD. INMT had a reference value in the diagnosis and prognostic estimation of LUAD. Gene set enrichment analysis showed that pathways of the cell cycle and DNA damage response were enriched in the INMT low-expression group. The top 10 hub genes upregulated in the INMT low-expression group mainly activated the cell cycle pathway. In addition, more frequently mutated TP53 genes, higher aneuploidy scores, a fraction of genomes altered, MANTIS scores, and tumor mutation burden were found in tumors with low expression of INMT. Furthermore, patients with low expression of INMT showed favorable clinical benefits to anti-PD-1 treatment with higher enrichment scores of immune-related signatures. Conclusion: The low expression of INMT was associated with poor prognosis but favorable immunotherapy response in LUAD. INMT may affect the progression of LUAD by regulating the cell cycle and may serve as a valuable independent prognostic biomarker in patients with LUAD.

Study protocol of an open-label prospective phase II umbrella study of precise neoadjuvant therapy for patients with stage II-IIIB resectable non-small cell lung cancer (PURPOSE).

Background: The outcomes of locally advanced non-small cell lung cancer (LA-NSCLC) are unfavorable mainly due to a high risk of cancer recurrence. Only around 5% of patients can benefit from perioperative chemotherapy which is the current standard treatment. Recently, promising results with neoadjuvant targeted and immune-therapy therapy have been seen. However, most clinical trials are looking for patients eligible for certain drugs, instead of seeking suitable treatments for certain patients. Therefore, it is necessary to look for more efficient perioperative therapies to increase resectability, reduce recurrence and improve prognosis. Methods/Design: The study is an open-label, prospective, phase II, umbrella trial, enrolling patients diagnosed with treatment-naïve potentially resectable Stage II-IIIB NSCLC. Next-generation sequencing (NGS) using a 68-gene panel is performed for biopsies of tumor tissues from eligible patients. Enrolled patients are then stratified into six independent cohorts based on the status of gene mutations and PD-L1 status in tumor tissues, that is, ①EGFR 19del group, ②EGFR 21 L858R group, ③EGFR rare mutation group, ④Other driver mutation group, ⑤Drive mutation-negative group with PD-L1≥1%, ⑥Drive mutation-negative group with PD-L1<1%. A Simon's two-stage design is performed in each cohort independently and patients receive corresponding standard therapies accordingly. We aim to enroll 26 patients in each cohort and totally 156 patients will be enrolled. The primary endpoint is objective response rate (ORR). Secondary endpoints include oncological prognosis and perioperative outcomes. Exploratory endpoint is to investigate patient-specific minimal residual disease (MRD) in predicting treatment efficacy and oncological prognosis. Discussions: This is the first umbrella trial focusing on the safety and efficacy of precise neoadjuvant therapy for patients diagnosed with potentially resectable LA-NSCLC based on NGS results. The results of this trial would help improve overall treatment results in LA-NSCLC patients. Trial registration: Chinese Clinical Trial Registry. Trial registration number: ChiCTR2100053021. Advantages and limitations of this study: There is no neoadjuvant umbrella trial focusing on LA-NSCLCs. This is the first neoadjuvant umbrella trial, using a precise individualized approach and seeking suitable drugs for LA-NSCLC patients, with the aim to improve overall treatment outcomes. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2100053021.

Surgical Outcomes of Video-Assisted versus Open Pneumonectomy for Lung Cancer: A Real-World Study.

BACKGROUND: The safety, feasibility and potential benefits of Video-assisted thoracoscopic surgery (VATS) pneumonectomy remain to be investigated. METHODS: Patients receiving VATS or Open pneumonectomy during the study period were included to compare surgical outcomes. Propensity-score matched (PSM) analysis was performed to eliminate potential biases. RESULTS: From 2013 to 2020, 583 consecutive patients receiving either VATS (105, 18%) or Open (478, 82%) pneumonectomy were included. Conversion from VATS to open was found in 20 patients (19.0%). The conversion patients had similar rates of major complications and perioperative mortality compared with the Open group. After PSM, 203 patients were included. No significant differences were observed in major complications and perioperative mortality between the two groups. For patients with stage pT2 tumors, the major complication rate in the VATS group was significantly lower than in the Open group (7.6% vs. 20.6%, p = 0.042). Compared with left pneumonectomy, the incidence of bronchopleural fistula (BPF) was significantly higher in right pneumonectomy for both VATS (0 vs. 16.7%, p = 0.005) and Open (0.7% vs. 6.5%, p = 0.002) approaches. CONCLUSIONS: Perioperative results of VATS pneumonectomy are non-inferior to those of the Open approach. Conversion to open surgery does not compromise perioperative outcomes. Patients with lower pT stage tumors who need pneumonectomy may benefit from VATS.

Carbon dot composites for bioapplications: a review.

Carbon dots (CDs) have received extensive attention in the last decade for their excellent optical, chemical and biological properties. In recent years, CD composites have also received significant attention due to their ability to improve the intrinsic properties and expand the application scope of CDs. In this article, the synthesis processes of four types of CD composites (metal-CD, nonmetallic inorganics-CD, and organics-CD as well as multi-components-CD composites) are systematically summarized first. Then the recent advancements in the bioapplications (bioimaging, drug delivery and biosensing) of these composites are also highlighted and discussed. Last, the current challenges and future trends of CD composites in biomedical fields are discussed.