Structure-based development of potent and selective type-II kinase inhibitors of RIPK1.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Analysis of Breast Cancer Screening Results and Influencing Factors of Breast Cancer in Guangdong Province from 2017 to 2021.

BACKGROUNDS: Breast cancer screening plays an important role in the early detection, diagnosis and treatment of breast cancer. The aim of this study was to evaluate the screening results and explore the influencing factors of breast cancer detection rate in Guangdong. METHODS: This cross-sectional study was conducted among 2,024,960 women aged 35-64 in Guangdong Province during 2017-2021. The data about breast cancer screening information were collected from the Guangdong maternal and child health information system. Descriptive statistical analysis was used to explain demographic characteristics and results of breast cancer screening. The generalized linear regression model was applied to analyze the related influencing factors of breast cancer detection rate. RESULTS: The estimated detection rate of breast cancer in Guangdong Province is 70.32/105, with an early diagnosis rate of 82.06%. After adjusting covariates, those women with older age (45-55 [OR (95% CI) 2.174 (1.872, 2.526)], 55-65 [OR (95% CI) 2.162 (1.760, 2.657)]), education for high school ([OR (95% CI) 1.491 (1.254, 1.773)]) and older age at first birth ([OR (95% CI) 1.632 (1.445, 1.844)]) were more likely to have higher detection rate of breast cancer. No history of surgery or biopsy ([OR (95% CI) 0.527 (0.387, 0.718)]), no history of breast cancer check ([OR (95% CI) 0.873 (0.774, 0.985)]) and no family history of breast cancer ([OR (95% CI) 0.255 (0.151, 0.432)]) women were more likely to screen negative for breast cancer (P < 0.05). CONCLUSION: The detection rate of breast cancer in screening showed an increasing trend year by year in Guangdong Province. Older age, education for high school and older age at first birth were risk factors for breast cancer detection rate, while no surgery or biopsy history, no family history of breast cancer and no history of breast cancer check were protective factors.

Strong electron-phonon coupling driven pseudogap modulation and density-wave fluctuations in a correlated polar metal.

There is tremendous interest in employing collective excitations of the lattice, spin, charge, and orbitals to tune strongly correlated electronic phenomena. We report such an effect in a ruthenate, Ca3Ru2O7, where two phonons with strong electron-phonon coupling modulate the electronic pseudogap as well as mediate charge and spin density wave fluctuations. Combining temperature-dependent Raman spectroscopy with density functional theory reveals two phonons, B2P and B2M, that are strongly coupled to electrons and whose scattering intensities respectively dominate in the pseudogap versus the metallic phases. The B2P squeezes the octahedra along the out of plane c-axis, while the B2M elongates it, thus modulating the Ru 4d orbital splitting and the bandwidth of the in-plane electron hopping; Thus, B2P opens the pseudogap, while B2M closes it. Moreover, the B2 phonons mediate incoherent charge and spin density wave fluctuations, as evidenced by changes in the background electronic Raman scattering that exhibit unique symmetry signatures. The polar order breaks inversion symmetry, enabling infrared activity of these phonons, paving the way for coherent light-driven control of electronic transport.

Advances in Online Detection Technology for Laser Additive Manufacturing: A Review.

In additive manufacturing (AM), the mechanical properties of manufactured parts are often insufficient due to complex defects and residual stresses, limiting their use in high-value or mission-critical applications. Therefore, the research and application of nondestructive testing (NDT) technologies to identify defects in AM are becoming increasingly urgent. This article reviews the recent progress in online detection technologies in AM, a special introduction to the high-speed synchrotron X-ray technology for real-time in situ observation, and analysis of defect formation processes in the past 5 years, and also discusses the latest research efforts involving process monitoring and feedback control algorithms. The formation mechanism of different defects and the influence of process parameters on defect formation, important parameters such as defect spatial resolution, detection speed, and scope of application of common NDT methods, and the defect types, advantages, and disadvantages associated with current online detection methods for monitoring three-dimensional printing processes are summarized. In response to the development requirements of AM technology, the most promising trends in online detection are also prospected. This review aims to serve as a reference and guidance for the work to identify/select the most suitable measurement methods and corresponding control strategy for online detection.

Implementing a novel capture and ligation probe-PCR method in mass screen and treatment to support malaria elimination efforts in the China-Myanmar border region.

BACKGROUND: Mass screening and treatment (MSAT) for malaria elimination lacks an ideal diagnostic tool to allow sensitive and affordable test of the target population in the field. This study evaluated whether Capture and Ligation Probe-PCR (CLIP-PCR) could be used in a field MSAT in Laiza City, Myanmar. METHODS: On day 0, two dried blood spots were collected from each participant. On day 1, all samples were screened for Plasmodium in a 20 m2 laboratory with workbench, a biosafety cabinet, a refrigerator, a benchtop shaking incubator and a qPCR machine, by four technicians using CLIP-PCR with sample pooling, at a health clinic of the Chinese bordering town of Nabang. On day 2, all positives were followed up and treated. RESULTS: Of 15,038 persons (65% of the total population) screened, 204 (1.36%) were CLIP-PCR positives. Among them, 188, 14, and 2 were infected with Plasmodium vivax, Plasmodium falciparum, and P. vivax/P. falciparum mix, respectively. The testing capacity was 538 persons/day, with a cost of US$0.92 /person. The proportion of submicroscopic infection was 64.7%. All positive individuals received treatment within 72 h after blood collection. CONCLUSION: Using CLIP-PCR in MSAT in low transmission settings can support the malaria elimination efforts in the China-Myanmar border region.

The public health response to an outbreak of border-spill malaria along China-Myanmar border.

INTRODUCTION: Malaria importation can be caused by cross-border movement either of both people and anopheline mosquitoes. However, there still lacks robust evidence of imported malaria caused by Plasmodium spp. infected anopheles along international border areas (border-spill malaria). The objectives of this study were to confirm whether an outbreak of Plasmodium vivax malaria is border-spill malaria and assess the effects of China's public health response along China-Myanmar border. METHODS: Epidemiological, parasitological and entomological investigations were conducted to investigate the outbreak of border-spill malaria. Meanwhile, comprehensive interventions were carried out to prevent further transmission and reintroduction of malaria. RESULTS: Rapid diagnostic testing, microscopy and polymerase chain reaction were performed and the infections were confirmed as P. vivax. A total of 22 (9.21%) of 239 workers contracted P. vivax during the outbreak. Multivariate logistic regression analysis identified that the distance of worker shelters in China within 300 meters to the internally displaced person (IDP) camps in Myanmar was a risk factors associated with malaria infection (adjusted odds ratio 7.5920; 95% confidence interval, 2.6079-22.1013; P = 0.0002). After comprehensive interventions, malaria transmission was successfully interpreted and prevented at the project site till the completion of project on 14 January 2020, and recurrence of P. vivax malaria was not detected by the end of 2020. CONCLUSION: This study provided robust evidence of border-spill malaria along China-Myanmar border. Malaria parasite reservoir and distance travelled by female anopheline mosquitoes are two determinants for border-spill malaria. The public health response to the outbreak indicates that the malaria surveillance and response system works well in preventing reintroduction of malaria. However, prevention of border-spill malaria is still a major challenge in the Yunnan border area, China.

Photo-Facilitated Detection and Sequencing of 5-Formylcytidine RNA.

5-Formylcytidine (f5 C) is one of the epigenetic nucleotides in tRNA. Despite the evident importance of f5 C in gene expression regulation, little is known about its exact amount and position. To capture this information, we developed a modification-specific functionalization with a semi-stabilized ylide. The chemical labelling exhibited a high selectivity towards f5 C and allowed distinction from similar 5-formyluridine. We realized a detection strategy based on the fluorescence signal of the cyclization product 4,5-pyridin-2-amine-cytidine paC, which exhibited a high quantum yield. The results clearly identified f5 C with a limit of detection at 0.58 nM. This method altered the hydrogen bonding activities of f5 C and modulated its reverse transcription signature in its sequencing profile. We showed that f5 C can be detected from tRNA segments with a single-base resolution. Taken together, this approach is a sensitive, antibody-free, and applicable detection and sequencing method for f5 C-containing RNA.

Historical review of malaria control and elimination in the border areas of China: A case study of Yunnan Province.

To understand how malaria could be eliminated in the original hyperendmic area for malaria along international borders in Yunnan Province, malaria situation and control were described on the basis of seven phases. At last the experiences and lessons of the program that reduced border malaria from hyperendmicity to malaria-free status were summarized. Malaria control and elimination area were particularly difficult in the Yunnan border. The achievement can be attributed to high political commitment, strategic and technical innovations based on the actual locality, effective collaboration and communication with neighbouring countries to carry out cross border interventions. Other border areas might perform their own pilot interventions based on their local context, including malaria burden, governing system, health service structure contextualized based on their socioeconomic development and ecology, and then a local decision could be made according to their own trial results.

Effectiveness of joint 3 + 1 malaria strategy along China-Myanmar cross border areas.

BACKGROUND: Cross-border malaria in Laiza City of Myanmar seriously affected Yingjiang County of China and compromised reaching the goal of malaria elimination by 2020. Since 2017, a pilot project on 3 + 1 strategy of joint cross-border malaria prevention and control was carried out for building a malaria buffer in these border areas. Here, 3 were the three preventive lines in China where different focalized approaches of malaria elimination were applied and + 1 was a defined border area in Myanmar where the integrated measures of malaria control were adopted. METHODS: A 5-year retrospective analysis (2015 to 2019) was conducted that included case detection, parasite prevalence and vector surveillance. Descriptive statistics was used and the incidence or rates were compared. The annual parasite incidence and the parasite prevalence rate in + 1 area of Myanmar, the annual importation rate in Yingjiang County of China and the density of An. minimus were statistically significant indictors to assess the effectiveness of the 3 + 1 strategy. RESULTS: In + 1 area of Myanmar from 2015 to 2019, the averaged annual parasite incidence was (59.11 ± 40.73)/1000 and Plasmodium vivax accounted for 96.27% of the total confirmed cases. After the pilot project, the annual parasite incidence dropped 89% from 104.77/1000 in 2016 to 12.18/1000 in 2019, the microscopic parasite prevalence rate dropped 100% from 0.34% in 2017 to zero in 2019 and the averaged density of An. Minimus per trap-night dropped 93% from 1.92 in June to 0.13 in September. The submicroscopic parasite prevalence rate increased from 1.15% in 2017 to 1.66% in 2019 without significant difference between the two surveys (P = 0.084). In Yingjiang County of China, neither indigenous nor introduced case was reported and 100% cases were imported from Myanmar since 2017. The averaged annual importation rate from 2015 to 2019 was (0.47 ± 0.15)/1000. After the pilot project, the annual importation rate dropped from 0.59/1000 in 2016 to 0.28/1000 in 2019 with an overall reduction of 53% in the whole county. The reduction was 67% (57.63/1000 to 18.01/1000) in the first preventive line, 52% (0.20/1000 to 0.10/1000) in the second preventive line and 36% (0.32/1000 to 0.22/1000) in the third preventive line. The averaged density of An. Minimus per trap-night in the first preventive line dropped 94% from 2.55 in June to 0.14 in September, without significant difference from that of + 1 area of Myanmar (Z value = - 1.18, P value = 0.24). CONCLUSION: The pilot project on 3 + 1 strategy has been significantly effective in the study areas and a buffer zone of border malaria was successfully established between Laiza City of Myanmar and Yingjiang County of China.

Quantitative analysis of phosphoproteome in necroptosis reveals a role of TRIM28 phosphorylation in promoting necroptosis-induced cytokine production.

Necroptosis is a form of regulated necrotic cell death that promotes inflammation. In cells undergoing necroptosis, activated RIPK1 kinase mediates the formation of RIPK1/RIPK3/MLKL complex to promote MLKL oligomerization and execution of necroptosis. RIPK1 kinase activity also promotes cell-autonomous activation of proinflammatory cytokine production in necroptosis. However, the signaling pathways downstream of RIPK1 kinase in necroptosis and how RIPK1 kinase activation controls inflammatory response induced by necroptosis are still largely unknown. Here, we quantitatively measured the temporal dynamics of over 7000 confident phosphorylation-sites during necroptosis using mass spectrometry. Our study defined a RIPK1-dependent phosphorylation pattern in late necroptosis that is associated with a proinflammatory component marked by p-S473 TRIM28. We show that the activation of p38 MAPK mediated by oligomerized MLKL promotes the phosphorylation of S473 TRIM28, which in turn mediates inflammation during late necroptosis. Taken together, our study illustrates a mechanism by which p38 MAPK may be activated by oligomerized MLKL to promote inflammation in necroptosis.

Intensive surveillance, rapid response and border collaboration for malaria elimination: China Yunnan's ''3 + 1''strategy.

BACKGROUND: Eliminating malaria and preventing re-establishment of malaria transmission in border areas requires universal coverage of malaria surveillance and a rapid response to any threats (i.e. malaria cues) of re-establishing transmission. MAIN TEXT: Strategy 1: Intensive interventions within 2.5 km-wide perimeter along the border to prevent border-spill malaria. The area within 2.5 km along the international border is the travel radius of anopheline mosquitoes. Comprehensive interventions should include: (1) proactive and passive case detection, (2) intensive vector surveillance, (3) evidence-based vector control, and (4) evidence-based preventative treatment with anti-malarial drugs. Strategy 2: Community-based malaria detection and screening of migrants and travellers in frontier townships. Un-permitted travellers cross borders frequently and present in frontier townships. Maintenance of intensified malaria surveillance should include: (1) passive malaria detection in the township hospitals, (2) seek assistance from villager leaders and health workers to monitor cross border travellers, and refer febrile patients to the township hospitals and (3) the county's Centre for Disease Control and Prevention maintain regular proactive case detection. Strategy 3: Universal coverage of malaria surveillance to detect malaria cues. Passive detection should be consolidated into the normal health service. Health services personnel should remain vigilant to ensure universal coverage of malaria detection and react promptly to any malaria cues. Strategy + 1: Strong collaborative support with neighbouring countries. Based on the agreement between the two countries, integrated control strategies should be carried out to reduce malaria burden for both countries. There should be a clear focus on the border areas between neighbouring countries. CONCLUSION: The 3 + 1 strategy is an experience summary of border malaria control and elimination, and then contributed to malaria elimination in Yunnan's border areas, China. Nevertheless, Yunnan still has remaining challenges of re-establishment of malaria transmission in the border areas, and the 3 + 1 strategy should still be carried out.

Malaria: elimination tale from Yunnan Province of China and new challenges for reintroduction.

BACKGROUND: Eradication of infectious disease is the sanctified public health and sustainable development goal around the world. MAIN BODY: Three antimalarial barriers were developed to control imported malarial cases, and an effective surveillance strategy known as the "1-3-7 approach" was developed to eliminate malaria from the Chinese population. From 2011 to 2019, 5254 confirmed malaria cases were reported and treated in Yunnan Province, China. Among them, 4566 cases were imported from other countries, and 688 cases were indigenous from 2011 to 2016. Since 2017, no new local malarial case has been reported in China. Thus, malaria has been completely eliminated in Yunnan Province. However, malaria is detected in overseas travellers on a regular basis, such as visitors from neighbouring Myanmar. CONCLUSION: Hence, the strategies should be further strengthened to maintain a robust public health infrastructure for disease surveillance and vector control programs in border areas. Such programs should be supported technically and financially by the government to avert the possibility of a malarial resurgence in Yunnan Province.

Electric Field-Induced Polarization Responses of Noncentrosymmetric Crystalline Biopolymers in Different Frequency Regimes - A Case Study on Unidirectionally Aligned ß-Chitin Crystals.

A dielectric medium containing noncentrosymmetric domains can exhibit piezoelectric and second-harmonic generation (SHG) responses when an electric field is applied. Since many crystalline biopolymers have noncentrosymmetric structures, there has been a great deal of interest in exploiting their piezoelectric and SHG responses for electromechanical and electro-optic devices, especially owing to their advantages such as biocompatibility and low density. However, exact mechanisms or origins of such polarization responses of crystalline biopolymers remain elusive due to the convolution of responses from multiple domains with varying degrees of structural disorder or difficulty of ensuring the unidirectional alignment of noncentrosymmetric domains. In this study, we investigate the polarization responses of a noncentrosymmetric crystalline biopolymer, namely, unidirectionally aligned ß-chitin crystals interspersed in the amorphous protein matrix, which can be obtained naturally from tubeworm Lamellibrachia satsuma (LS) tube. The mechanisms governing polarization responses in different dynamic regimes covering optical (>1013 Hz), acoustic/ultrasonic (103-105 Hz), and low (10-2-102 Hz) frequencies are explained. Relationships between the polarization responses dominant in different frequencies are addressed. Also, electromechanical coupling responses, including piezoelectricity of the LS tube, are quantitatively discussed. The findings of this study can be applicable to other noncentrosymmetric crystalline biopolymers, elucidating their polarization responses.

Seven decades towards malaria elimination in Yunnan, China.

BACKGROUND: Yunnan Province was considered the most difficult place in China for malaria elimination because of its complex malaria epidemiology, heterogeneous ecological features, relatively modest economic development, and long, porous border with three malaria endemic countries: Lao People's Democratic Republic, Myanmar, and Viet Nam. METHODS: Academic publications and grey literature relevant to malaria elimination in Yunnan covering the period from 1950 until 2020 inclusive were considered. The following academic indexes were searched: China Science Periodical Database, China National Knowledge Infrastructure Database, and MEDLINE. Grey literature sources were mainly available from the National Institute of Parasitic Diseases (NIPD), the Chinese Center for Diseases Control and Prevention, and the Yunnan Institute of Parasitic Diseases (YIPD). RESULTS: A malaria elimination campaign in the 1950-1960s, based mainly on mass administration of antimalarial drugs and large-scale vector control, reduced morbidity and mortality from malaria and interrupted transmission in some areas, although elimination was not achieved. Similar strategies were used to contain outbreaks and a resurgence of disease during the 1970s, when malaria services were discontinued. From the 1980s, malaria incidence declined, despite the challenges of large numbers of mobile and migrant populations and an unstable primary health care system in rural areas following economic transformation. Launch of the national malaria elimination programme in 2010 led to adoption of the '1-3-7' surveillance and response strategy specifying timely detection of and response for every case, supported by the establishment of a real-time web-based disease surveillance system and a new primary health care system in rural areas. Border malaria was addressed in Yunnan by strengthening the surveillance system down to the lowest level, cross-border collaboration with neighbouring countries and non-governmental organizations, and the involvement of other sectors. CONCLUSIONS: Seven decades of work to eliminate malaria in Yunnan have shown the importance of political commitment, technically sound strategies with high quality implementation, a robust surveillance and response system at all levels, community participation and effective management of border malaria. The experiences and lessons learned from elimination remain important for prevention re-establishment of malaria transmission in the Province.

Shear-induced unidirectional deposition of bacterial cellulose microfibrils using rising bubble stream cultivation.

In crystalline cellulose I, all glucan chains are ordered from reducing ends to non-reducing ends. Thus, the polarity of individual chains is added forming a large dipole within the crystal. If one can engineer unidirectional alignment (parallel packing) of cellulose crystals, then it might be possible to utilize the material properties originating from polar crystalline structures. However, most post-synthesis manipulation methods reported so far can only achieve the uniaxial alignment with bi-directionality (antiparallel packing). Here, we report a method to induce the parallel packing of bacterial cellulose microfibrils by applying unidirectional shear stress during the synthesis and deposition through the rising bubble stream in a culture medium. Driving force for the alignment is explained with mathematical estimation of the shear stress. Evidences of the parallel alignment of crystalline cellulose Iα domains were obtained using nonlinear optical spectroscopy techniques.

Cocrystalline Polymer Films Exhibiting Second-Order Nonlinear Optical Properties.

Tailored polymer materials exhibiting high-glass transition temperatures, cross-linked matrices, and/or strong intermolecular interactions containing electric-field poled nonlinear optical (NLO) chromophores are promising materials for applications in optical telecommunication, high-performance computing, and data transmission. Although the current design parameters have led to significant advances in NLO materials, we introduce an alternative, yet highly effective, approach in which a NLO chromophore is cocrystallized with a polymer, forming a noncentrosymmetric hybrid host-guest complex. Specifically, poly(ethylene oxide) (PEO) and 2-chloro-4-nitroaniline (CNA) will cocrystallize and exhibit second harmonic generation (SHG) activity due to the formation of a noncentrosymmetric cocrystalline unit cell where the chromophore exhibits acentric alignment. Furthermore, the hybrid PEO/CNA films exhibit interesting SHG activity at elevated temperature in which SHG intensity decreases to zero when the cocrystal orientation randomizes due to sample melting. Aligning and maintaining a cocrystalline domain orientation via the formation of hybrid host-guest complexes, while imparting SHG properties, is an innovative approach for creating materials exhibiting SHG properties.

Chirality-Dependent Second Harmonic Generation of MoS2 Nanoscroll with Enhanced Efficiency.

Materials with high second harmonic generation (SHG) efficiency and reduced dimensions are favorable for integrated photonics and nonlinear optical applications. Here, we fabricate MoS2 nanoscrolls with different chiralities and study their SHG performances. As a 1D material, MoS2 nanoscroll shows reduced symmetry and strong chirality dependency in the polarization-resolved SHG characterizations. This SHG performance can be well explained by the superposition theory of second harmonic field of the nanoscroll walls. MoS2 nanoscrolls with certain chiralities and diameters in our experiment can have SHG intensity up to 95 times stronger than that of monolayer MoS2, and the full potential can still be further exploited. The same chirality-dependent SHG can be expected for nanoscrolls or nanotubes composed of other noncentrosymmetric 2D materials, such as WS2, WSe2, and hBN. The characterization and analysis results presented here can also be exploited as a nondestructive technique to determine the chiralities of these nanoscrolls and nanotubes.

High-Pressure Synthesis and Ferrimagnetism of Ni3TeO6-Type Mn2ScMO6 (M = Nb, Ta).

The corundum-related oxides Mn2ScNbO6 and Mn2ScTaO6 were synthesized at high pressure and high temperature (6 GPa and 1475 K). Analysis of the synchrotron powder X-ray diffraction shows that Mn2ScNbO6 and Mn2ScTaO6 crystallize in Ni3TeO6-type noncentrosymmetric crystal structures with space group R3. The asymmetric crystal structure was confirmed by second harmonic generation measurement. X-ray absorption near-edge spectroscopies indicate formal valence states of Mn2+2Sc3+Nb5+O6 and Mn2+2Sc3+Ta5+O6, also supported by the calculated bond valence sums. Both samples are electrically insulating. Magnetic measurements indicate that Mn2ScNbO6 and Mn2ScTaO6 order ferrimagnetically at 53 and 50 K, respectively, and Mn2ScTaO6 is found to have a field-induced magnetic transition.

Approaching the Intrinsic Limit in Transition Metal Diselenides via Point Defect Control.

Two dimensional (2D) transition-metal dichalcogenide (TMD) based semiconductors have generated intense recent interest due to their novel optical and electronic properties and potential for applications. In this work, we characterize the atomic and electronic nature of intrinsic point defects found in single crystals of these materials synthesized by two different methods, chemical vapor transport and self-flux growth. Using a combination of scanning tunneling microscopy (STM) and scanning transmission electron microscopy (STEM), we show that the two major intrinsic defects in these materials are metal vacancies and chalcogen antisites. We show that by control of the synthetic conditions, we can reduce the defect concentration from above 1013/cm2 to below 1011/cm2. Because these point defects act as centers for nonradiative recombination of excitons, this improvement in material quality leads to a hundred-fold increase in the radiative recombination efficiency.

Ir6In32S21, a polar, metal-rich semiconducting subchalcogenide.

Subchalcogenides are uncommon, and their chemical bonding results from an interplay between metal-metal and metal-chalcogenide interactions. Herein, we present Ir6In32S21, a novel semiconducting subchalcogenide compound that crystallizes in a new structure type in the polar P31m space group, with unit cell parameters a = 13.9378(12) Å, c = 8.2316(8) Å, α = ß = 90°, γ = 120°. The compound has a large band gap of 1.48(2) eV, and photoemission and Kelvin probe measurements corroborate this semiconducting behavior with a valence band maximum (VBM) of -4.95(5) eV, conduction band minimum of -3.47(5) eV, and a photoresponse shift of the Fermi level by ∼0.2 eV in the presence of white light. X-ray absorption spectroscopy shows absorption edges for In and Ir do not indicate clear oxidation states, suggesting that the numerous coordination environments of Ir6In32S21 make such assignments ambiguous. Electronic structure calculations confirm the semiconducting character with a nearly direct band gap, and electron localization function (ELF) analysis suggests that the origin of the gap is the result of electron transfer from the In atoms to the S 3p and Ir 5d orbitals. DFT calculations indicate that the average hole effective masses near the VBM (1.19m e) are substantially smaller than the average electron masses near the CBM (2.51m e), an unusual feature for most semiconductors. The crystal and electronic structure of Ir6In32S21, along with spectroscopic data, suggest that it is neither a true intermetallic nor a classical semiconductor, but somewhere in between those two extremes.