Sensitivity of Botrytis cinerea from Vineyards to Boscalid, Isofetamid, and Pydiflumetofen in Shandong Province, China.

Succinate dehydrogenase inhibitor (SDHI) fungicides are the most commonly and effectively used class of fungicides for controlling gray mold. Among them, only boscalid has been registered in China for controlling grape gray mold, whereas isofetamid and pydiflumetofen are two new SDHI fungicides that have demonstrated high efficacy against various fungal diseases. However, the sensitivity of Botrytis cinerea isolates from vineyards in China to these three fungicides is currently unknown. In this study, the sensitivity of 55 B. cinerea isolates from vineyards to boscalid, isofetamid, and pydiflumetofen was determined, with the effective concentrations for inhibiting 50% of spore germination (EC50) values ranging from 1.10 to 393, 0.0300 to 42.0, and 0.0990 to 25.5 µg ml-1, respectively. The resistance frequencies for boscalid, isofetamid, and pydiflumetofen were 60.0, 7.2, and 12.8%, respectively. Three mutations (H272R, H272Y, and P225F) were detected in the SdhB subunit, with H272R being the most prevalent (75.7%), followed by H272Y (16.2%) and P225F (8.1%). All three mutations are associated with resistance to boscalid, and of them, H272R mutants exhibited high resistance. Only P225F and H272Y mutants exhibited resistance to isofetamid and pydiflumetofen, respectively. A weakly positive cross-resistance relationship was observed between boscalid and pydiflumetofen (r = 0.38, P < 0.05). Additionally, the H272R mutants showed no significant fitness costs, whereas the remaining mutants exhibited reduced mycelial growth (P225F) and sporulation (H272Y and P225F). These results suggest that isofetamid and pydiflumetofen are effective fungicides against B. cinerea in vineyards, but appropriate rotation strategies must be implemented to reduce the selection of existing SDHI-resistant isolates.

The High Value of External Anal- and Urethral-Sphincter Electromyography in Differential Diagnosis with MSA-P, PD, and PSP.

Objective: It is a challenge to differentiate multiple system atrophy parkinsonism (MSA-P), Parkinson's disease (PD), and progressive supranuclear palsy (PSP). We aimed to explore the value of external anal-sphincter electromyography (EAS-EMG) and urethral-sphincter electromyography (US-EMG) in differential diagnosis with MSA-P, PD, and PSP. Methods: A total of 149 subjects, including 27 MSA-P, 100 PD, and 22 PSP, were recruited. The average duration and amplitude of motor unit potentials (MUPs), percentage of polyphasic MUPs, amplitude during strong contraction, and recruitment pattern during maximal voluntary contraction were recorded. The differences in EAS-EMG and US-EMG results between MSA-P, PD, and PSP were analyzed. Results: In EAS-EMG examination, the average duration of MUPs of MSA-P was significantly longer than that of PD and PSP; the percentage of polyphasic MUPs and the ratio of simple phase and simple-mix phase of MSA-P and PSP were significantly higher than that of PD; the amplitude during strong contraction of MSA-P was significantly lower than that of PD. In US-EMG examination, the average duration of MUPs in male MSA-P was significantly longer than that in male PD and PSP; the ratio of simple phase and simple-mix phase in male MSA-P was significantly higher than that in male PD; there was no statistical difference in US-EMG indexes between male PD and PSP male. And because only one female PSP was examined, only female MSA-P and PD were compared, the average duration of MUPs in female MSA-P was significantly longer than that in female PD; the ratio of simple phase and simple-mix phase in female MSA-P was significantly higher than that in female PD. Conclusion: The average duration of MUPs and the ratio of the simple phase and simple-mix phase of EAS-EMG and US-EMG all can provide the basis for the differential diagnosis between MSA-P and PD. US-EMG can be used as a supplement to differentiate MSA-P from PD when EAS-EMG is limited. The only discriminating indicator between MSA-P and PSP seems to be the average duration of MUPs of EAS-EMG and US-EMG. There is still a lack of diagnostic electromyography indicators between PD and PSP.

Dapagliflozin-affected endothelial dysfunction and altered gut microbiota in mice with heart failure.

Aim: To investigate the potential microbiome profile of a mouse model with heart failure (HF) during dapagliflozin treatment. Method: An HF model was constructed in 8-week-old male mice, and cardiac tissues were analyzed using histological staining. Hemodynamic indexes were measured, and fecal samples were collected for 16S rDNA sequencing. Chao1, Shannon, and Simpson were used for α-diversity analysis. b-Diversity analysis was conducted using principal coordinate analysis (PCoA) and non-metric multidimensional scaling (NMDS) based on the Bray-Curtis distance. Linear discriminant analysis coupled with effect size measurements (LEfSe) was used to identify signature gut microbiota, and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was used to predict the function of altered gut microbiota. Result: Dapagliflozin treatment reduced inflammation, infarction area, and cardiac fibrosis in HF mice. It also increased endothelial-dependent dilation and inflammation in mice with HF. Dapagliflozin decreased the ratio of Firmicutes/Bacteroidetes, which was increased in HF mice. There was no significant statistical difference in α-diversity among the control, HF, and HF+dapagliflozin groups. Desulfovibrio, AF12, and Paraprevotella were enriched in HF+dapagliflozin, while Rikenella and Mucispirillum were enriched in HF based on LEfSe. KEGG analysis revealed that altered gut microbiota was associated with fermentation, amino acid biosynthesis, nucleoside and nucleotide biosynthesis/degradation, fatty acid and lipid biosynthesis, carbohydrate biosynthesis/degradation, and cofactor/prosthetic group/electron carrier/vitamin biosynthesis. Conclusion: Understanding the microbiome profile helps elucidate the mechanism of dapagliflozin for HF. The signature genera identified in this study could be used as a convenient method to distinguish between HF patients and healthy individuals.

Role of the CXCR6/CXCL16 axis in autoimmune diseases.

The C-X-C motif ligand 16, or CXCL16, is a chemokine that belongs to the ELR - CXC subfamily. Its function is to bind to the chemokine receptor CXCR6, which is a G protein-coupled receptor with 7 transmembrane domains. The CXCR6/CXCL16 axis has been linked to the development of numerous autoimmune diseases and is connected to clinical parameters that reflect disease severity, activity, and prognosis in conditions such as multiple sclerosis, autoimmune hepatitis, rheumatoid arthritis, Crohn's disease, and psoriasis. CXCL16 is expressed in various immune cells, such as dendritic cells, monocytes, macrophages, and B cells. During autoimmune diseases, CXCL16 can facilitate the adhesion of immune cells like monocytes, T cells, NKT cells, and others to endothelial cells and dendritic cells. Additionally, sCXCL16 can regulate the migration of CXCR6-expressing leukocytes, which includes CD8+ T cells, CD4+ T cells, NK cells, constant natural killer T cells, plasma cells, and monocytes. Further investigation is required to comprehend the intricate interactions between chemokines and the pathogenesis of autoimmune diseases. It remains to be seen whether the CXCR6/CXCL16 axis represents a new target for the treatment of these conditions.

The Characteristics of Cognitive Proficiency in Patients with Acute Neuromyelitis Optica Spectrum Disease and its Correlation with Serum Aquaporin-4 Antibody Titer.

Objective: To explore the characteristics and dynamic evolution of cognitive impairment in patients with neuromyelitis optica spectrum disorder (NMOSD). Methods: Twenty-five patients with acute NMOSD and 30 age-matched healthy individuals were consecutively recruited in this study. The Montreal Cognitive Assessment (MoCA), Chinese Version of Rey Auditory Vocabulary Learning Test (CRAVLT), Verbal Fluency Test (VFT), Digital Span Test (DST), Paced Auditory Serial Addition Task 3/2s version (PASAT-3/2), Rey−Osterrieth Complex Figure Test (ROCF) and Stroop Color and Word Test (CWT) were used to evaluate cognitive function. The correlations between cognitive function and serum aquaporin-4 (AQP-4) antibody titer were analyzed. Results: Sixty-four percent of patients with acute NMOSD had cognitive dysfunction. MoCA (p < 0.001), CRAVLT-N7 (p = 0.004), CRAVLT-N8 (p = 0.011), ROCF-C (p = 0.005), ROCF-R (p < 0.001), PASAT-3 (p = 0.013), PASAT-2 (p = 0.001) and CWT-A (p = 0.017) were significantly worse in patients with acute NMOSD than those in control group. During follow-up visits, significant differences of serum AQP-4 antibody titers were still noted in NMOSD patients (p < 0.001), while no significant differences were found by MoCA. Conclusion: A high number of patients with acute NMOSD suffer from cognitive dysfunction. Serum AQP-4 antibody titers can decrease during disease remission, while obvious cognitive decline in these patients still exists.

Patients with Asian-type DEL can safely be transfused with RhD-positive blood.

Red blood cells (RBCs) of Asian-type DEL phenotype express few RhD proteins and are typed as serologic RhD-negative (D-) phenotype in routine testing. RhD-positive (D+) RBC transfusion for patients with Asian-type DEL has been proposed but has not been generally adopted because of a lack of direct evidence regarding its safety and the underlying mechanism. We performed a single-arm multicenter clinical trial to document the outcome of D+ RBC transfusion in patients with Asian-type DEL; none of the recipients (0/42; 95% confidence interval, 0-8.40) developed alloanti-D after a median follow-up of 226 days. We conducted a large retrospective study to detect alloanti-D immunization in 4045 serologic D- pregnant women throughout China; alloanti-D was found only in individuals with true D- (2.63%, 79/3009), but not in those with Asian-type DEL (0/1032). We further retrospectively examined 127 serologic D- pregnant women who had developed alloanti-D and found none with Asian-type DEL (0/127). Finally, we analyzed RHD transcripts from Asian-type DEL erythroblasts and examined antigen epitopes expressed by various RHD transcripts in vitro, finding a low abundance of full-length RHD transcripts (0.18% of the total) expressing RhD antigens carrying the entire repertoire of epitopes, which could explain the immune tolerance against D+ RBCs. Our results provide multiple lines of evidence that individuals with Asian-type DEL cannot produce alloanti-D when exposed to D+ RBCs after transfusion or pregnancy. Therefore, we recommend considering D+ RBC transfusion and discontinuing anti-D prophylaxis in patients with Asian-type DEL, including pregnant women. This clinical trial is registered at www.clinicaltrials.gov as #NCT03727230.

Molecular and serological analysis of the D variant in the Chinese population and identification of seven novel RHD alleles.

BACKGROUND: The molecular basis of the D variant phenotype in the Chinese differs greatly from that of the Caucasian. Adapting a specific D typing strategy to the spectrum of prevalent RHD variant alleles is necessary. STUDY DESIGN AND METHODS: Blood samples with ambiguous D phenotypes were collected in the Southern Chinese population. A special three-step typing strategy was applied. First, the common DVI type 3 was identified from epitope profiles of D antigen. Then, another common weak D type 15 (RHD*845A) was identified by epitope profiles of D antigen and Sanger sequencing of RHD exon 6. Finally, the remaining D variants were genotyped mainly by Sanger sequencing. For the novel RHD alleles in the coding region and exon-intron junction, in vitro transfection and minigene splicing assays were performed, respectively. The anti-D investigation was performed. RESULTS: DVI type 3 (65/253, 25.7%) and weak D type 15 (62/253, 24.5%) were common Chinese D variants, and RHD*960A, DFR, RHD*weak D type 25, 72, and 136 were frequent variant RHD alleles. Besides, twenty-two sporadic and seven novel RHD alleles (RHD*188A; RHD*688C; RHD*782 T; RHD*1181C; RHD*165 T, 993A; RHD*148 + 3G > T and RHD*1227 + 5G > C) were identified. The deleterious effect of the novel RHD alleles on D antigen or mRNA expression was confirmed. Anti-D was detected in two DVI type 3 pregnant women. DISCUSSION: The three-step typing strategy provides an effective approach for Chinese D variant typing. It can be anticipated that commercially available RHD genotyping kits have limitations for testing Chinese D variants, as some of the frequent variants are not interrogated.

Chromosome 1q21 gain is an adverse prognostic factor for newly diagnosed multiple myeloma patients treated with bortezomib-based regimens.

Chromosome 1q21 aberration is one of the most common cytogenetic abnormalities in multiple myeloma, and is considered an important prognostic factor. The present study analyzed the clinical relevance and prognostic impact of 1q21 gain in 194 patients with newly diagnosed multiple myeloma treated with bortezomib-based regimens. 1q21 gain was detected in 45.9% (89/194) of patients, and those with 1q21 gain had a worse prognosis. Strikingly, our results showed that excluding the effects of other coinciding genetic anomalies, patients carrying at least four copies of 1q21 had worse survival outcome. Moreover, del(13q) strongly correlates with 1q21 gain, and the coexistence of del(13q) and 1q21 gain plays an important role in reducing PFS and OS times. Therefore, 1q21 gain should be considered a high-risk feature in multiple myeloma patients treated with a bortezomib-based regimen.

Systematic analysis of prognostic significance, functional enrichment and immune implication of STK10 in acute myeloid leukemia.

BACKGROUND: Despite deeper understanding of the genetic landscape of acute myeloid leukemia (AML), the improvement of survival is still a great challenge. STK10 is overexpressed in several cancers with functions varying according to cancer types. But the functions of STK10 in AML has never been reported. METHODS: We analyzed the expression, prognosis and potential functions of STK10 utilizing public web servers. Metascape and the String database were used for functional and protein-protein interaction analyses. RESULTS: We found STK10 was enriched in blood & immune cells and overexpressed in AML. High STK10 expression was associated with poor overall survival, which was also identified in the subgroups of patients ≤ 60 years old and patients with non-high-risk cytogenetics. We demonstrated genes associated with STK10 were enriched in blood, spleen and bone marrow, influencing the immune function and biological process of AML. ITGB2 and ITGAM might directly interact with STK10 and were associated with poor prognosis. Besides, STK10 was associated with the infiltration of immune cells and immune checkpoints, like HLA-E, CD274 and GAL-9. CONCLUSIONS: The present study was the original description of STK10 in AML and set the stage for developing STK10 as a new prognostic marker or therapeutic target for AML.

Secondary alloanti-D immunization post transfusion of "Asia type" DEL red blood cells.

BACKGROUND: "Asia type" DEL red blood cells (RBCs) express a very weak D antigen and cannot be detected by routine RhD typing. Thus, it is routinely typed as D-negative (D-) blood group and transfused to D- recipients. Here we described a case of secondary alloanti-D immunization that was associated with transfusion of DEL RBCs to D- recipients and was initially considered as primary alloanti-D immunization. CASE PRESENTATION: A 44-year-old D- woman (G2P2) with adenomyosis and anemia underwent transabdominal hysterectomy. She received four units of D- RBCs before operation. Before transfusion, the alloantibody screening test was negative. Four days after the first transfusion, she needed another RBC transfusion. Unexpectedly, the routine pre-transfusion alloantibody screening test became positive and anti-D (titer, 128-fold) was identified, indicating an alloanti-D immunization. The anti-D developed four days after the first transfusion was unexplained, so alloantibody identification was performed on the sample collected before the first transfusion, and weak anti-D combined with anti-E, which was not detectable during the previous routine pre-transfusion alloantibody screening test with non-enzyme-treated screening cells, was identified using bromelain-treated panel cells. The remaining blood samples of first transfusion in bag tails from two donors were collected for RHD genotyping analysis. One donor was later identified as "Asia type" DEL having RHD* 1227 A/01 N.01 genotype. CONCLUSION: Caution should be applied when we conclude that transfusion of "Asia type" DEL RBCs to true D- recipients could induce primary alloanti-D immunization, especially if the short time interval between transfusion and detection of anti-D is observed.

Development and Validation of a Novel Prognostic Model for Overall Survival in Newly Diagnosed Multiple Myeloma Integrating Tumor Burden and Comorbidities.

Background: Multiple myeloma (MM) is a highly heterogeneous disease with enormously variable outcomes. It remains to be a major challenge to conduct a more precise estimation of the survival of MM patients. The existing stratifications attached less importance to the prognostic significance of comorbidities. In the present study, we aimed to develop and validate a novel and simple prognostic stratification integrating tumor burden and comorbidities measured by HCT-CI. Method: We retrospectively enrolled 385 consecutive newly diagnosed multiple myeloma (NDMM) patients in Xijing Hospital from January 2013 to December 2020. The cohort between January 2016 and December 2020 was selected as development cohort (N = 233), and the cohort between January 2013 and December 2015 was determined as validation cohort (N = 152). By using LASSO analysis and univariate and multivariable Cox regression analyses, we developed the MM-BHAP model in the way of nomogram composed of ß2-MG, HCT-CI, ALB, and PBPC. We internally and externally validated the MM-BHAP model and compared it with ISS stage and R-ISS stage. Results: The MM-BHAP model was superior to the ISS stage and partially better than the R-ISS stage according to time-dependent AUC, time-dependent C-index, DCA, IDI, and continuous NRI analyses. In predicting OS, only the MM-BHAP stratification clearly divided patients into three groups while both the ISS stage and R-ISS stage had poor classifications in patients with stage I and stage II. Moreover, the MM-BHAP stratification and the R-ISS stage performed well in predicting PFS, but not for the ISS stage. Besides, the MM-BHAP model was also applied to the patients with age ≤65 or age >65 and with or without HRCA and could enhance R-ISS or ISS classifications. Conclusions: Our study offered a novel simple MM-BHAP stratification containing tumor burden and comorbidities to predict outcomes in the real-world unselected NDMM population.

HMGB1 Promotes Lymphangiogenesis through the Activation of RAGE on M2 Macrophages in Laryngeal Squamous Cell Carcinoma.

Background: Receptor for advanced glycation end products (RAGE) is implicated in tumor biology. Released high mobility group box protein 1 (HMGB1) ligand binding to RAGE receptor in tumor cells promotes tumor progression. The mechanisms of HMGB1-RAGE signaling in M2 macrophages involved in lymphangiogenesis in laryngeal carcinoma remain poorly understood. Here, we assessed the effect of HMGB1-RAGE signaling on M2 macrophages in lymphangiogenesis. Methods: HMGB1, CD163, and D2-40 in laryngeal squamous cell carcinoma (LSCC, n = 123), laryngeal precursor lesions (LPLs, n = 102), and vocal polyp (VP, n = 55) were analyzed by immunohistochemistry. THP-1 cell-expressed RAGE gene was knocked down and then polarized to M0 macrophages and M2 macrophages. IL-23, TNF-α, TGF-ß, and IL-10 were measured by ELISA; IL-1ß, IL-12, IL-10, and CCL-13 were evaluated by RT-qPCR, and CD206, CD163, and RAGE were evaluated by western blot to evaluate whether classical M2 macrophages were obtained. Conditioned media from RAGE+/- M0 macrophages and RAGE+/- M2 macrophages incubated in the presence or absence of HMGB1, anti-Toll-like receptor (TLR)2, anti-TLR4 antibodies, and anti-VEGF-C antibodies were collected separately for human dermal lymphatic endothelial cells (HDLEC) for proliferation, migration, lymphangiogenesis assay, and VEGF-C concentration analysis. Results: HMGB1 and M2 macrophage densities were increased in LSCC (P < 0.01). HMGB1 and M2 macrophage densities were significantly correlated with lymphatic vessel density (LVD) in LSCC (P < 0.01). The HMGB1 overexpression and higher M2 macrophage density were involved in lymph node metastasis (P < 0.01) and poor prognosis (P < 0.05). In vitro, conditioned medium from HMGB1-stimulated RAGE+ M2 macrophages activated lymphangiogenesis by upregulating the VEGF compared to controls (P < 0.05). On the contrary, RAGE knockdown obviously decreased the corresponding effects of HMGB1-preconditioned M2 macrophages upon HDLEC (P < 0.05). HMGB1-TLR pathway does not significantly increase HDLEC proliferation, migration, and lymphangiogenesis on M2 macrophages. Conclusions: HMGB1 promotes lymphangiogenesis by activation of RAGE on M2 macrophages. Targeting RAGE may provide an effective therapeutic strategy against M2 macrophages in LSCC patients with lymph node metastasis.

Insight into the Double-Edged Role of Ferroptosis in Disease.

Ferroptosis, a newly described type of iron-dependent programmed cell death that is distinct from apoptosis, necroptosis, and other types of cell death, is involved in lipid peroxidation (LP), reactive oxygen species (ROS) production, and mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury, cancer, hepatic fibrosis, Parkinson's disease, and Alzheimer's disease. Therefore, ferroptosis has become one of the research hotspots for disease treatment and attracted extensive attention in recent years. This review mainly summarizes the relationship between ferroptosis and various diseases classified by the system, including the urinary system, digestive system, respiratory system, nervous system. In addition, the role and molecular mechanism of multiple inhibitors and inducers for ferroptosis are further elucidated. A deeper understanding of the relationship between ferroptosis and multiple diseases may provide new strategies for researching diseases and drug development based on ferroptosis.

Serological screening and genetic analysis of RhCE variants in the Chinese Southern Han donors.

OBJECTIVES: To screen RhCE variants in the Chinese Southern Han donors for molecular genetic analysis. BACKGROUND: More than hundreds of RhCE variant alleles have been described to resulting in weak and/or partial expression of RhCE antigens, generation of low-prevalence antigens and/or absence of a high-prevalence antigen of Rh system, which mainly reported in the people of African origin. In this study, the serological screening and molecular genetic analysis of RhCE variants were performed in the Chinese Southern Han donors. METHODS: The blood samples of E(+) donors were preliminarily collected. Then, RhCE antigens of the E(+) samples were further typed by using two sets of monoclonal anti-C, anti-c, anti-e and another anti-E. When weak expression of RhCE antigens was found, direct sequencing for 10 exons of RHCE gene, RH genotyping analysis by using multiplex ligation-dependent probe amplification, flow cytometric analysis and even cDNA sequencing were performed. RESULTS: A total of 4487 E(+) samples were collected and four samples with weak expression of antigens were detected. RHCE*Ce375G and RHCE*Ce667T variant alleles were identified in two samples with weak expression of e antigen, respectively. But no variant alleles were found in another two samples with weak expression of C antigen. CONCLUSION: The variant RHCE*Ce375G validated by mRNA sequencing and the deduced RHCE*Ce667T alleles were firstly identified in the Chinese population. The DCE haplotype might account for the weak expression of C antigen in two donors.

Genome-Wide Characterization of HSP90 Gene Family in Cucumber and Their Potential Roles in Response to Abiotic and Biotic Stresses.

Heat shock protein 90 (HSP90) possesses critical functions in plant developmental control and defense reactions. The HSP90 gene family has been studied in various plant species. However, the HSP90 gene family in cucumber has not been characterized in detail. In this study, a total of six HSP90 genes were identified from the cucumber genome, which were distributed to five chromosomes. Phylogenetic analysis divided the cucumber HSP90 genes into two groups. The structural characteristics of cucumber HSP90 members in the same group were similar but varied among different groups. Synteny analysis showed that only one cucumber HSP90 gene, Csa1G569290, was conservative, which was not collinear with any HSP90 gene in Arabidopsis and rice. The other five cucumber HSP90 genes were collinear with five Arabidopsis HSP90 genes and six rice HSP90 genes. Only one pair of paralogous genes in the cucumber HSP90 gene family, namely one pair of tandem duplication genes (Csa1G569270/Csa1G569290), was detected. The promoter analysis showed that the promoters of cucumber HSP90 genes contained hormone, stress, and development-related cis-elements. Tissue-specific expression analysis revealed that only one cucumber HSP90 gene Csa3G183950 was highly expressed in tendril but low or not expressed in other tissues, while the other five HSP90 genes were expressed in all tissues. Furthermore, the expression levels of cucumber HSP90 genes were differentially induced by temperature and photoperiod, gibberellin (GA), downy mildew, and powdery mildew stimuli. Two cucumber HSP90 genes, Csa1G569270 and Csa1G569290, were both differentially expressed in response to abiotic and biotic stresses, which means that these two HSP90 genes play important roles in the process of cucumber growth and development. These findings improve our understanding of cucumber HSP90 family genes and provide preliminary information for further studies of cucumber HSP90 gene functions in plant growth and development.

Treatment options for older unfit patients with acute myeloid leukemia.

Older acute myeloid leukemia patients usually experience a bleak outcome, especially those in the unfit group. For this unfit category, intensive chemotherapy and allogeneic stem cell transplantation are usually accompanied by higher early mortality, which results from higher risk genetic profiles and worse psychological and physiological conditions. The significant improvement in genetic technology recently has driven the appearance of several mutation-targeted therapies, such as FLT3, Bcl-2, IDH and Hedgehog pathway inhibitors and an anti-CD33 antibody-drug conjugate, which have changed enormously the therapeutic landscape of acute myeloid leukemia. This review describes the treatment dilemma of the unfit group and discusses the objective clinical data of each targeted drug and mechanisms of resistance, with a focus on combination strategies with fewer toxicities and abrogation of drug resistance.

Heptamethine Cyanine-Based Application for Cancer Theranostics.

Cancer is the most common life-threatening malignant disease. The future of personalized cancer treatments relies on the development of functional agents that have tumor-targeted anticancer activities and can be detected in tumors through imaging. Cyanines, especially heptamethine cyanine (Cy7), have prospective application because of their excellent tumor-targeting capacity, high quantum yield, low tissue autofluorescence, long absorption wavelength, and low background interference. In this review, the application of Cy7 and its derivatives in tumors is comprehensively explored. Cy7 is enormously acknowledged in the field of non-invasive therapy that can "detect" and "kill" tumor cells via near-infrared fluorescence (NIRF) imaging, photothermal therapy (PTT), and photodynamic therapy (PDT). Furthermore, Cy7 is more available and has excellent properties in cancer theranostics by the presence of multifunctional nanoparticles via fulfilling multimodal imaging and combination therapy simultaneously. This review provides a comprehensive scope of Cy7's application for cancer NIRF imaging, phototherapy, nanoprobe-based combination therapy in recent years. A deeper understanding of the application of imaging and treatment underlying Cy7 in cancer may provide new strategies for drug development based on cyanine. Thus, the review will lead the way to new types with optical properties and practical transformation to clinical practice.